Chemical Agents of Opportunity for Terrorism: TICs & TIMs

Chemical Agents of 

Opportunity for 

Terrorism: TICs & TIMs 

Non-Procedure Participant Guide 

December, 2008

Chemical Agents of Opportunity for Terrorism 

Training Support Package 

Participant Guide 

Table of Contents 

Chemical Agents of Opportunity for Terrorism: TICs & TIMs - Introduction..................... 1 

Module One Toxic Warfare: Looking Beyond Conventional Chemical Weapons - 

Administration Page ..................................................................................................................... 2 

Duration ...................................................................................................................................... 2 

Scope Statement.......................................................................................................................... 2 

Terminal Learning Objective (TLO) .......................................................................................... 2 

Enabling Learning Objectives (ELO) ......................................................................................... 2 

Resources .................................................................................................................................... 2 

Instructor to Participant Ratio..................................................................................................... 3 

Reference List ............................................................................................................................. 3 

Practical Exercise Statement....................................................................................................... 3 

Assessment Strategy ................................................................................................................... 4 

Module One ................................................................................................................................... 5 

Icon Map ..................................................................................................................................... 5 

Module One Summary ............................................................................................................... 65 

Module Two The Clinical Neurotoxicology of Chemical Terrorism - Administration Page 

....................................................................................................................................................... 66 

Duration .................................................................................................................................... 66 

Scope Statement........................................................................................................................ 66 

Terminal Learning Objective (TLO) ........................................................................................ 66 

Enabling Learning Objectives (ELO) ....................................................................................... 66 

Resources .................................................................................................................................. 66 

Instructor to Participant Ratio................................................................................................... 66 

Reference List ........................................................................................................................... 66 

Practical Exercise Statement..................................................................................................... 67 

Assessment Strategy ................................................................................................................. 67 

Module Two................................................................................................................................. 68 

Icon Map ................................................................................................................................... 68 

Module Two Summary............................................................................................................. 118 

Module Three Toxic Industrial Gases as Terrorist Threats - Administration Page ......... 120 

Duration .................................................................................................................................. 120 

Scope Statement...................................................................................................................... 120 

Terminal Learning Objective (TLO) ...................................................................................... 120 

Enabling Learning Objectives (ELO) ..................................................................................... 120 

Resources ................................................................................................................................ 120 

Instructor to Participant Ratio................................................................................................. 121 

Reference List ......................................................................................................................... 121 

Practical Exercise Statement................................................................................................... 123 

Assessment Strategy ............................................................................................................... 123 

December 2008 Version 2.0 Page i




Module Three ............................................................................................................................ 124 

Icon Map ................................................................................................................................. 124 

Module Three Summary .......................................................................................................... 181 

Module Four Cyanide & Fumigants - Administration Page ............................................... 182 

Duration .................................................................................................................................. 182 




Resources ................................................................................................................................ 182 





Module Four.............................................................................................................................. 187 

Icon Map ................................................................................................................................. 187 

Module Four Summary ............................................................................................................ 247 

Module Five Chemical Contamination of Food, Water, & Medication - Administration 

Page ............................................................................................................................................ 249 

Duration .................................................................................................................................. 249 




Resources ................................................................................................................................ 249 





Module Five ............................................................................................................................... 255 

Icon Map ................................................................................................................................. 255 

Module Five Summary ............................................................................................................. 303 

Module Six Terrorism through Fear & Uncertainty: Delayed Toxic Syndromes - 

Administration Page ................................................................................................................. 304 

Duration .................................................................................................................................. 304 




Resources ................................................................................................................................ 304 





December 2008 Version 2.0 Page ii




Module Six ................................................................................................................................. 308 

Icon Map ................................................................................................................................. 308 

Module Six Summary ............................................................................................................... 355 

Module Seven Radiation Emergencies - Administration Page............................................ 357 

Duration .................................................................................................................................. 357 




Resources ................................................................................................................................ 358 





Module Seven ............................................................................................................................ 363 

Icon Map ................................................................................................................................. 363 

Module Seven Summary........................................................................................................... 421 

Module Eight Observed Behaviors during Mass Chemical Exposures- Administration 

Page ............................................................................................................................................ 423 

Duration .................................................................................................................................. 423 




Resources ................................................................................................................................ 423 





Module Eight ............................................................................................................................. 428 

Icon Map ................................................................................................................................. 428 

Module Eight Summary ........................................................................................................... 468 

December 2008 Version 2.0 Page iii




Chemical Agents of Opportunity for Terrorism: TICs & TIMs - 

Introduction 

In recent years, there has been growing concern that many of the most likely threats of chemical 

terrorism involve so-called “agents of opportunity.” Both common and unusual industrial agents 

may pose a considerable threat as potential terrorist weapons. While an understanding of the 

traditional military chemical weapons (e.g. nerve agents) remains essential, an appreciation of 

the myriad of other potential toxic chemicals readily available in our society is crucial if we are to 

optimally prepare, identify and defend against chemical threats. Many toxic industrial chemicals 

are easily obtainable from multiple sources in our communities and pose a serious threat to 

health if accidentally released or intentionally disseminated. 

The American College of Medical Toxicology (ACMT) has designed a 1-day course: “Chemical 

Agents of Opportunity for Terrorism: TICs (Toxic Industrial Chemicals) and TIMs (Toxic 

Industrial Materials)”. This course will utilize a symptom-based clinical approach to describe the 

medical impact of various chemical poisons. It will provide a framework to enhance recognition 

of the common health effects of apparently disparate chemical toxins, describe the risk to 

various healthcare workers, and introduce clinical and public health management strategies. 

The traditional military warfare chemical agents will not be covered in these lectures because 

information on these agents is readily accessible through a number of other forums such as the 

Internet. 

The central course topics are presented in eight modules and include: 

• Toxic Warfare: Looking Beyond Conventional Chemical Weapons 

• The Clinical Neurotoxicology of Chemical Terrorism 

• Toxic Industrial Gases 

• Cyanide & Fumigants 

• Chemical Contamination of Food, Water, & Medications 

• Terrorism through Fear & Uncertainty: Delayed Toxic Syndromes 

• Radiation Emergencies 

• Observed Behaviors during Mass Chemicals Exposures 

December 2008 Version 2.0 Page 1




Module One 

Toxic Warfare: Looking Beyond Conventional Chemical 

Weapons - Administration Page 

While the threat of conventional chemical warfare has received much attention, and is the 

subject of tight control measures and a program of planned chemical destruction, less interest 

has been paid to other chemical agents that have great potential to wreak havoc on the civilian 

sector and produce mass casualties. This module provides an introduction and overview of the 

Chemical Agents of Opportunity for Terrorism: TICs (Toxic Industrial Chemicals) and TIMs 

(Toxic Industrial Materials) course and seeks to provide awareness-level training on a variety of 

toxic syndromes likely to be encountered following exposures to TICs, TIMs and other chemical 

agents of opportunity. 

Duration 

45 minutes 

Scope Statement 

This module presents a broad overview of the potential toxic industrial chemicals and toxic 

metals readily available in our society, the most likely scenarios that might occur as the result of 

terrorism, and historical examples of major chemical events. A framework for early detection 

and recognition of toxic chemicals is provided in order to optimally prepare, identify, and defend 

against chemical threats. 

Terminal Learning Objective (TLO) 

• Understand the concept of chemical agents of opportunity, including 

specific Toxic Industrial Chemicals (TICs) and Toxic Industrial 

Materials (TIMs) 

Enabling Learning Objectives (ELO) 

Resources 

• Define Toxic Industrial Chemicals and Toxic Industrial Materials 

• Describe the goals of toxic terrorism 

• Discuss prioritization and legislative response to chemicals of concern 

• Introduce the concept of using clinical findings to identify a terrorist 

chemical agent and event 

• Review historical examples of toxic terrorism 

Each of the eight course modules is deployed as an interactive, instructor-lead, MS PowerPoint 

presentation containing didactic content, historical examples, and selected case studies. All 

presentations are included in a printed participant guide (PG) containing the modules’ overview, 

scope statement, terminal and enabling learning objectives, PowerPoint slide handouts, and a 

summary section. 





Instructor to Participant Ratio 

1:8 (minimum) and 1:25 (maximum) 

Reference List 

1. Acute Exposure Guideline Levels (AEGL): www.epa.gov/oppt/aegl/ 

2. Army Office of the Surgeon General. Draft Medical NBC Hazard Analysis of 

Chemical-Biological-Radiological-Nuclear-High Explosive Threat, Hospital Scenarios 

and Planning Requirements. Oct 2001. 

3. Bach LK and Walton B. “Las Vegas Dodged a Bullet: Chlorine-hauling tanker rolls 

free. Workers able to board, activate brake.” Las Vegas Review Journal, 30 Aug 

2007. Last accessed Dec 2008 from: http://www.lvrj.com/news/9466232.html 

4. Brodsky BH. “Industrial Chemicals as Weapons: Chlorine” Monterey Institute of 

International Studies, 31 July 2007. Last access Dec 2008 from: 

http://www.nti.org/e_research/e3_89.html 

5. CDR Joseph L. Hughart and Mark M. Bashor. ATSDR: Industrial Chemicals And 

Terrorism: Human Health Threat Analysis, Mitigation And Prevention. 

6. “Chemical Time Bombs”. Editorial. New York Times, 10 May 2005. Last accessed 

Dec 2008 from: http://www.nytimes.com/2005/05/10/opinion/10tues1.html 

7. Congressional Research Service. “Chemical Plant Security” CRS Web, 23 Jan 2003. 

Last access Dec 2008 from: 

http://www.ncseonline.org/nle/crsreports/03Feb/RL31530.pdf 

8. Hauschild VD. Prioritizing industrial chemical hazards. J Toxicol Environ Health 

2005;68:857-76. 

9. International Task Force 25. “Hazard from Toxic Industrial Chemicals” 18 March 

1996. Last access Dec 2008 from: http://wikileaks.org/leak/us-uk-ca-mou-itf25- 

1996.pdf 

10. Khan AS and Sage MJ (2000) Biological and Chemical Terrorism: Strategic Plan for 

Preparedness and Response, Recommendations of the CDC Strategic Planning 

Workgroup. MMWR, 49(RR04);1-14. 

11. Monterrey Institute: http://montrep.miis.edu/databases.html 

12. Okumura, T. et. al. The Tokyo Subway Sarin Attack: Disaster Management. 

Academic Emergency Medicine, Vol. 5. p. 613-628. 1998. 

13. Staten CL. “The Terrorist Threat of Chemical Attack” EmergencyNet News, 27 Apr 

2005. Last accessed Dec 2008 from: 

http://www.emergency.com/2005/chem_attk2005.htm 

14. Tucker, Jonathan (editor). Toxic Terror: Assessing Terrorist Use of Chemical and 

Biological Weapons. MIT Press, 2000. 

15. USA Patriot Act, HR 3162, 107th Congress, 1st Session (2001). Last accessed Dec 

2008 from: epic.org/privacy/terrorism/hr3162.html. 

Practical Exercise Statement 

Each module presentation contains one or more interactive audience response questions 

designed to drive discussion, promote participant engagement, and test knowledge. Through 





the use of the Meridia® Audience Response system, participant responses can be collected, 

tabulated, and displayed within the presentation in real time. In order to use the interactive 

slides accompanying this presentation, the lecture hall must be equipped with the Meridia® 

Audience Response system and user keypads. In addition, a copy of the “Meridia® Q&A” 

software component for MS PowerPoint must be installed on the presenter’s computer. 

Assessment Strategy 

Participant progress toward course learning objectives is monitored through informal discussion 

and responses to each module’s practical exercise questions. Overall mastery of module 

content and concepts is documented by means of a comprehensive, end-of-day posttest 

touching on key learning objectives from each module. Each participant must obtain a score of 

80% or better to successfully complete the training and obtain a course completion certificate. 





Module One 

Icon Map 

Knowledge Check: Used when it is time to assess the learners’ understanding 

Example: Used when there is a descriptive illustration to show or explain 

Key Points: Used to convey essential learning concepts, discussions and introduction of 

supplemental material 

Hint: Used to cover administrative items or instructional tips that aid in the flow of the 

instruction 





Slide 1 

Chemical Agents of Opportunity for Terrorism: TICs & TIMs 

Module One 

Toxic Warfare: Looking Beyond Conventional 

Chemical Weapons 


This module is entitled: Toxic Warfare: Looking Beyond Conventional Chemical Weapons. 

1 





Slide 2 

Chemical Agents of Opportunity for Terrorism: 

TICs & TIMs 

Course Overview 

• Why “Agents of Opportunity ” 

• Neurotoxicology 

• Gases 

• Cyanide and Fumigants 

• Food/Water/Medications 

• Delayed Onset Toxins 

• Radiation 

• Psychological Aspects 

Module One – Toxic Warfare: Looking Beyond Conventional Chemical Weapons 

2 

This course was developed by the American College of Medical Toxicology (ACMT) to 

prepare participants for chemical terrorism threats not traditionally discussed in other 

training courses. 

The topics that will be covered today start with an overview of the topic “Why Agents of 

Opportunity”, followed by neurotoxins, then inhalational agents such as gases, 

systemic toxins such as cyanide, means of delivery such as food and water, toxins with 

delayed onset, the effects of radiation exposure, and finally the psychological aspects of 

mass exposure to toxins. 





Slide 3 

The objectives of the agents of opportunity course are: to define toxic industrial 

chemicals (TICs) and toxic industrial materials (these are things such as explosives and 

radiologicals) (TIMs), describe the goals of toxic terrorism, discuss prioritization lists and 

the appropriate community response to chemicals of concern. This course will provide 

examples of terrorist events or chemical accidents to introduce the concept of using 

clinical findings to identify and respond to these events. 

The focus of the first module is to provide you with a broad overview and principles that 

will be developed throughout the rest of the day’s interactions. 

This module will use historical examples of toxic terrorism to explain how the prehospital, 

public health, law enforcement, and medical communities can be better prepared for the 

medical needs of patients. 





Slide 4 



Audience Response 

Which of the following best describes the type of work 

you do 

1. Clinical Medicine or Nursing 

2. First Responder 

3. Law Enforcement 

4. Military 

5. Public Health 

6. Other 


4 





Slide 5 




Which of the following best describes who you work 

for 

1. Federal Government (incl. Military) 

2. State Government 

3. Local Government (incl. Police, Fire, EMS) 

4. Educational (University, High School, …) 

5. Hospital or Medical Facility 

6. Corporation 

7. Consulting Firm 

8. Other 


5 





Slide 6 



Official “Battlefield” 

Chemical Warfare Agents 

• Purpose Designed Warfare 

Agents 

• Dual Use Industrial 

Chemicals 

– Nerve ( eg. Sarin, VX) 

– Blister ( eg. Mustard) 

– Blood ( eg. CN) 

– Choking ( eg.Phosgene ) 

– 1° focus of chemical defense 

programs in past 

– Less emphasis on industrial 

chemicals as a military threat 


6 

This course covers Chemical Agents of Opportunity- a novel approach to this subject of 

chemical terrorism. In general, these agents do not have any civilian use and are 

“purpose designed” for warfare or human harm, and they are very difficult to obtain. 

However, other battleground agents are actually dual use industrial chemicals. While the 

military has weaponized them and some of them have seen battlefield use in the past, 

they also have significant industrial applications. They are not the types of chemicals 

that can be solely restricted to military use and military stockpiles. Given their dual use, 

they are much more accessible than the military-use only agents. 

This module will not be covering the “select agent” chemicals. Sarin and VX are two 

potent organophosphorus compounds developed for use by the military. They are called 

nerve agents due to their ability to produce prominent neuromuscular weakness 

compared to the classical organophosphorus agents like parathion, which produces 

more muscarinic findings (e.g., salivation, bronchorrhea, miosis). Sulfur mustard is one 

example of a vesicant (blister forming) agent, also developed for military use. The nerve 

agents and blister agents do not have any conventional or industrial use. Demilitarization 

programs are reducing the stockpiles of these agents. 

The blood agents include cyanide and cyanogen chloride. These have military use and 

also have industrial uses such as in mining and chemical syntheses. 

The choking agents include irritant gases such as phosgene and chlorine. These have 

proven military use in WWI and still have widespread industrial applications. 

These categorization terms, such as choking and blood agents, were developed by the 

military and not semantically medical in use. Blood agent, for example, is a vague term 

that could suggest that the toxin damages the blood. But in military use, it suggests that 

the toxin inhibits the oxygen carrying capacity of the blood. This too is incorrect, since 

cyanide affects oxygen utilization not its delivery. 





Slide 7 



TICs and TIMs 

• TIC = Toxic Industrial Chemical 

• TIM = Toxic Industrial Material 

• Chemical substance that in sufficient available 

quantity produces a toxic effect through inhalation, 

ingestion, or other route of absorption 


7 

TICs are toxic industrial chemicals and TIMs are toxic industrial materials. These are 

terms first introduced by the military to distinguish industrial chemicals of concern from 

the traditional weaponized battlefield agents such as sarin and mustard gas. TICs and 

TIMs are chemical substances, that delivered properly in sufficient quantity may produce 

a toxic effect. This effect may be via the exposure route of inhalation, ingestion, dermal 

absorption, or, more rarely, parenteral injection. These chemicals must be “delivered 

properly” in “sufficient quantity” to be problematic. 





Slide 8 




Which of the following would best be characterized as 

a toxic industrial compound 

1. Ammonia 

2. Anthrax 

3. Sarin 

4. Mustard Gas 

5. Water 


8 





Slide 9 



Importance of DOSE 

“All substances are poisons: there is none which is not a poison. 

The right dose differentiates a poison and a remedy." 

Paracelsus (1493 -1541) 


9 

It was the noted toxicologist Paracelsus who made the following observation in the 16 th 

century: “All substances are poisons: there is none which is not a poison. The right dose 

differentiates a poison and a remedy.” 

As you can see on this slide, along the X-axis (dose), as you increase the dose, the 

response, along the Y-axis (response) increases. The response could be response to a 

therapy (a good thing) or it could be lethality (not a good thing). Hence as you increase 

the dose, at some point you get some sort of response. 

“Dose response” is a tenet of toxicology. At sufficiently low doses everything is nontoxic, 

even things we think of as “really toxic.” As the dose goes up, everything, even water or 

oxygen, become toxic. The “toxicity” of a compound is in large part related to how much 

the dose must rise to get a response. 

This graph holds true for an individual or for a population. If used for a population, 

response is generally the percent of individuals who display the expected response. 

This curve shows a “ceiling effect” to the effect. If this were a lethality curve, the point at 

which it flattened out at the top would be the LD100, or the lethal dose for 100% of the 

population. 





Slide 10 



Sources of TICs and TIMs (1) 


10 

Unlike the battlefield chemical agents which are highly secured and tightly controlled, 

TICs and TIMs are ubiquitous. Two seemingly innocuous sources of highly toxic 

chemicals are farm and garden supply stores and college laboratories. College 

laboratories, particularly those involved in research as opposed to education, contain 

many toxic chemicals, often in large volumes, and are another source for obtaining TICs 

and TIMS. 

Examples of some of the agents found in these other sites include: 

o Airports use jet fuel, and transport toxic chemicals in the airplanes. 

o Farm and garden supply stores have pesticides. 

o 

o 

Toxic waste dumps are obvious sources of a variety of chemicals deemed to be 

hazardous to human health. 

Glass plants contain large amounts of arsenic and thallium. 





Slide 11 



Sources of TICs and TIMs (2) 


11 

Other sources of TICs and TIMs include medical facilities which utilize a large number of 

cancer chemotherapeutic agents which are highly toxic by design and also store and 

utilize a variety of radio nuclides diagnostically and therapeutically. 

A major concern about radiological terrorism involves the use of stolen hospital-based 

radio nuclides, given their extensive availability. Although the quantity may be small, the 

psychological impact of their use in a “dirty bomb” scenario is profound. 

Many of these chemical threats involve chemicals that are routinely transported 

throughout our country by rail and other bulk transporter systems. If the chemicals of 

concern were limited to fixed facilities, the challenges would be significant enough. 

Propane tank leaks lead to asphyxiation, and explosions can cause massive destruction. 

But understanding that highly toxic chemicals are moving all across our county through 

our towns and villages brings the specter of chemical toxic disasters - whether deliberate 

or accidental - into everyone’s backyard. 





Slide 12 



Chemical Terrorism 

• Definition – the use of chemicals to harm or alter the 

behavior of an adversary 

• Utilizes existing stored chemicals – exploiting 

weapons of opportunity 

• Who’s at risk 

– Civilians in U.S. 

• Wide availability of toxic materials throughout U.S. 

• Proximity of industrial operations to large urban centers 

– Military abroad 


12 

Although there is no strict definition of “chemical terrorism”, it generally refers to the use 

of chemicals to harm or alter the behavior of an adversary. [CDC] Unlike conventional 

military warfare, chemical terrorists utilize readily available chemicals. By utilizing stored 

or other readily available chemicals reference to these chemicals as “weapons or 

chemicals of opportunity” is made more clear. US civilians remain at risk given the easy 

availability of many industrial and commercial chemicals, and particularly those civilians 

living near large urban areas where the terrorism targets are very dense. The military 

abroad, while at risk for conventional chemical weapons, is also at risk for agents of 

opportunity. This was demonstrated by the use of chlorine gas released against the 

military in Iraq in 2007. 





Slide 13 



Goals of Toxic Terrorism 

• Health Effects 

– Incapacitating vs killing 

• Damage / contamination of infrastructure 

• Psychological effects resulting from actual or 

threatened use of toxic substances - terrorizing 

– Asymmetrical 

– Create uncertainty, fear, and panic 

– Uncertainties provide tactical and/or psychological 

advantages 


13 

Another difference between the battlefield military chemicals and many of the industrial 

chemicals of concern is that the former are meant to kill while the latter may not always 

be fatal except at very high doses. At lower doses, they may incapacitate – physically or 

emotionally or financially. 

As an example, the intended goal of the terrorist use of some chemicals, and certainly 

the radiologicals, is to damage or contaminate infrastructure. Such contamination by 

itself may create havoc and be extraordinarily disruptive. 

Even the intended threat of chemical exposure may prove terrorizing. Potential exposure 

may create uncertainty, fear, and panic. Such uncertainties provide the terrorist with an 

asymmetrical advantage, and provide tactical and psychological advantages. Tactical in 

this context mean short-term and supportive of the ultimate goal. 





Slide 14 




The goal of toxic terrorism is best accomplished by 

which of the following scenarios or releases 

1. Immediately lethal agent release in restaurant 

2. Disruption of a transportation corridor 

3. Creating fear leading to incapacity 

4. Occult insertion of a carcinogen 

5. Targeting a single factory component 


14 





Slide 15 



Scenarios 

• Large-scale outdoor release of toxic gas or fumes, 

and/or an explosion, from an attack on a mobile or 

fixed tank or vessel 

• Targeted release of a toxic gas into a confined 

space (e.g. a subway, theater, or building) or against 

specific individuals or groups 

• Acute or delayed poisoning by contamination of 

food, water, or a highly trafficked venue 


15 

There are a number of possible or probable scenarios that involve chemicals of 

opportunity. Three such scenarios include: a large-scale outdoor chemical release from 

an attack on a mobile or fixed facility, a targeted release of a toxic gas into a small 

enclosed area or confined space, and acute or delayed poisoning by contamination of 

food, water, or a highly trafficked venue. 

In the first scenario, a large scale outdoor release will potential affect the greatest 

number of people, depending on the nature of the agent (e.g., volatility, density) and the 

prevailing conditions. Even in an area without fixed facilities, vulnerability still exists due 

to the transportation of hazardous materials in large quantities (e.g., chlorine tank car, 90 

tons). 

In the second scenario, release in a closed space allows a smaller dose to be utilized to 

generate a similar clinical effect due to the lack of dilution by ambient air or wind. 

Recognize that the words ‘confined space’ here is not meant to be synonymous with the 

OSHA (Occupational Safety and Health Administration) definition, in which a confined 

space is one with limited egress. We use it to refer to a small space or one contained by 

walls and ceiling. 

In the third scenario, administration of the agent by contamination of a point source 

could still affect a large number of people, particularly if a delayed onset agent is utilized. 





Slide 16 



Why Use Industrial Chemicals 


16 

This is a photograph of a large industrial plant that could be the target of a terrorist 

event. It would be considered a fixed facility. 





Slide 17 



Limitations with Purpose: 

Designed WMD 

Aum Shinrikyo – Matsumoto 

1994, Tokyo 1995 ( Sarin) 

• Spent ~$30 million on chemical 

weapons research 

• Employed many scientists 

• Killed only 19 

• Problems with 

– Production 

– Effective Delivery System 


17 

One of the worst “chemical terrorism" incidents on civilians involved the release of the 

deadly nerve agent sarin in the Tokyo subway in 1995. This terrorist group – often 

referred to as a “sect” prior to this incident – was known as Aum Shinrikyo and was led 

by what some considered a god-like guru – Shoko Asahara. This group had a number 

of highly educated scientists as its members, and they apparently spent ~$30 million or 

more on chemical weapons research. 

Problems in producing truly weapon-grade sarin (estimates were that the product was 




Slide 18 



More Effective: Bhopal (1984) 

• Methyl isocyanate 

• > 2,500 deaths 

• 60,000 injuries 


18 

Contrast the Sarin Tokyo subway release with what occurred in Bhopal India 11 years 

earlier. This accidental release of methyl isocyanate at a chemical production facility 

involved in the production of the carbamate pesticide, Sevin®, resulted in over 2,500 

deaths and 60,000 injuries. The Bhopal incident will be discussed in further detail in the 

module on toxic gases. 





Slide 19 



Should We Worry 

• ~ 850,000 U.S. businesses use, produce, or store 

TICs 

• EPA report – 123 chemical plants across US have 

enough toxic chemicals to kill/injure 1 million people 

in terrorist attack 

• 750 other plants have enough chemicals to kill/injure 

at least 100,000 people in an attack 

• U.S. army study - terrorist attack on chemical plant 

in densely populated area could result in 2.4 million 

fatalities or injuries 


19 

Should we worry 

Industrial facilities are omnipresent. According to one report, 850,000 U.S. businesses 

use, produce, or store toxic industrial chemicals. The EPA has suggested that 123 

chemical plants in 24 states across US have enough toxic chemicals to kill/injure 1 

million people in terrorist attack. [NYT] In addition, another 750 plants have enough 

chemicals to kill/injure at least 100,000 people. These are worst case estimates based 

on the EPA’s Risk Management Program. 

There is obviously no way to know conclusively the number who will die or be injured in 

the release of a chemical into the environment, and all of the models created to predict 

this suffer their own individual limitations. For example, wind dispersion and rain may 

result in a different outcome (with more or fewer injuries than predicted). Nonetheless, 

the numbers are numbing. 





Slide 20 




20 

This is a Toxic Release Inventory map prepared by ATSDR shows the location of high 

volume chemical production facilities in the U.S. that produce greater than 100,000 

pounds of chemicals from the year 2000. 

Each blue dot represents a facility containing more than 100,000 pounds, while the more 

darkly shaded areas represent the scale of danger based on density of available 

chemical(s). 

As you can see, these plants are in every state and virtually every locality. In some 

parts of the country - such as the heavily trafficked and populated northeast corridor and 

the Gulf coast - these chemical production plants are in great abundance, increasing the 

threat. 





Slide 21 





Slide 22 



US Legislative Response to Major 

Chemical Accidents 

• Emergency Planning and Community Right -to-Know 

Act (EPCRA) 1986 

• Clean Air Act Amendments of 1990 

– Occupational Safety & Health Administration ’s (OSHA) 

Process Safety Management (PSM) 

– Environmental Protection Agency ’s (EPA) Risk 

Management Program (RMP) 1996 


22 

There have been legislative responses to major chemical incidents including the EPCRA 

in response to Bhopal. 

The tragedy at Bhopal in December 1984, followed by a subsequent release of aldicarb 

oxime from a facility in Institute, West Virginia, resulted in great public concern in the 

United States about the potential danger posed by major chemical accidents. This public 

concern triggered the passage of three different legislative programs. 

The first law specifically intended to address the problem of chemical accidents in the 

US was the Emergency Planning and Community Right-to-Know Act of 1986 (EPCRA; 

Public Law 99-499). The other two legislative programs addressing chemical releases 

were enacted under sections 304 and 112(r), respectively, of the Clean Air Act 

Amendments of 1990 (Public Law 101-549). The first of these was the Occupational 

Safety and Health Administration’s (OSHA) Process Safety Management (PSM) 

standard (29CFR Part 1910), which required facilities having specified hazardous 

chemicals to implement accident prevention measures designed to protect workers. 

The most recent program, arising from section 112(r)(7) of the Clean Air Act 

Amendments, was the U.S. Environmental Protection Agency’s (EPA’s) Risk 

Management Program (40 CFR Part 68), issued on June 20, 1996. 





Slide 23 



Emergency Planning & Community 

Right-to-Know Act (EPCRA) 

• Required chemical facilities to provide 

– Information necessary for emergency planning to Local Emergency 

Planning Committees ( LEPCs) 

– annual hazardous chemical inventories to State Emergency Respons e 

Commissions (SERCs), LEPCs and local fire departments. 

• Required SERCs & LERCs to prepare emergency response 

plans for chemical accidents. 

• Established Toxics Release Inventory (TRI), which requires 

facilities to annually report quantities of their emissions of 

toxic chemicals to TRI database. 


23 

EPCRA requires states to create State Emergency Response Commissions (SERCs), 

and communities to form Local Emergency Planning Committees (LEPCs) to prepare 

local emergency response plans for chemical accidents. 

It also requires chemical facilities to provide LEPCs with information necessary for 

emergency planning, and to submit to SERCs, LEPCs and local fire departments annual 

inventory reports (Tier 2 reports) and information about hazardous chemicals. 

The statute also established the Toxics Release Inventory (TRI), which requires certain 

facilities to annually report the quantities of their emissions of toxic chemicals. The 

chemical inventory data are available to the public on a limited basis and EPA maintains 

a national database containing TRI reports. 





Slide 24 



EPA: Risk Management Program 

• Aim: Prevent/minimize consequences of accidental 

chemical releases from fixed facilities. 

• Facilities that manufacture, process, use, store, or 

otherwise handle any of 140* listed substances at or 

above specified threshold quantities (range from 

500–20,000 pounds) must submit a Risk 

Management Plan (RMP). 

* The number of chemicals has been increased to 650 


24 

Going beyond just reporting type and amount of chemicals at a site, the risk 

management plan (RMP) sought to have those facilities/companies provide a plan to 

respond to and mitigate an ACCIDENTAL release. 





Slide 25 



Risk Management Programs 

(61 CFR 31667, 06/20/96) 

• Hazard vulnerability assessment 

• Accident prevention program 

• Emergency response program 

• Specified facility information 

• Make info available to: EPA, state & local 

governments, FD & public 


25 

An accidental release prevention program is designed to detect, prevent, and minimize 

accidental releases. An emergency response program is designed to protect human 

health and the environment. 





Slide 26 



Worst-Case Scenario: 

Likelihood of Occurrence 

• WCS are considered unlikely because: 

– assume a very large release occurring during worst -case 

atmospheric conditions 

– does not include active release mitigation such as water 

deluge systems and automatic shutoff valves 

• passive mitigation efforts included, such as containment dikes a 

building enclosures 

• However, with terrorist attack, more than one 

process likely to be affected 

nd 


26 

The EPA’s regulations require that Risk Management Plan (RMPs) be developed by all 

companies with large quantities of toxic chemicals on site. They should specify a worst 

case scenario (WCS). The modeling features of WCS include calm wind conditions 

(allowing uniform spread of agent in all directions from a release), and release of all the 

substance involved in a single process or storage site without including any active 

mitigation steps (attempts to control spread). 

These conditions are all unlikely to occur, but as we will discuss later, the models are 

designed for accidental releases. A terrorist release may involve multiple processes or 

targets. 

The use of a worst-case scenario is standard practice in modeling hazardous material 

release responses and performing risk assessment. It allows an understanding of the 

potential for an event, with a realistic endpoint for response preparedness. In the 

situation of a real event, the response can be scaled as needed. 





Slide 27 



AEGL Plumes 

Acute Exposure Guideline Levels (AEGL): www.epa.gov/oppt/aegl / 


27 

One of the criteria used to assist in the determination of the response criteria is the 

plume model shown here. This takes into account ambient wind condition from a point 

release. EPA has developed a number of Acute Emergency Guideline Levels (AEGL) for 

various chemical compounds and duration of exposure. AEGLs serve as a planning tool 

for response to chemical releases from chemical facilities. Note that AEGL-3 is more 

severe than AEGL-1. 

AEGL-1 is the airborne concentration (as parts per million, ppm) of a substance above 

which it is predicted that the general population, including susceptible individuals, could 

experience notable discomfort, irritation, or certain asymptomatic nonsensory effects. 

However, the effects are not disabling and are transient and reversible upon cessation of 

exposure. 

AEGL-2 is the airborne concentration (ppm) of a substance above which it is predicted 

that the general population, including susceptible individuals, could experience 

irreversible or other serious, long-lasting adverse health effects or an impaired ability to 

escape. 

AEGL-3 is the airborne concentration (ppm) of a substance above which it is predicted 

that the general population, including susceptible individuals, could experience lifethreatening 

health effects or death 





Slide 28 



Reductions in Hazards & 

Vulnerabilities 

Safe Hometown Guide 


28 

An ultimate goal of emergency planning, including legislative efforts, would be to reduce 

the risk to surrounding communities by encouraging “hardening” of facilities and 

decreasing the available “dose” of toxic compounds (Hardening implies increases the 

safety and security of a facility and the chemicals it stores). 

In this example, from “Safe Hometown Guide”, reducing the storage capacity, enclosing 

vulnerable storage vessels, or even relocating civilian populations can help to reduce the 

effect of an unexpected chemical release. 

Many of these are common sense maneuvers, but are avoided due to costs and the 

belief that such a release is unlikely. Had the shantytowns around the Union Carbide 

plant in Bhopal been relocated, for example, the devastation would have likely been 

substantially reduced. 





Slide 29 



http://www.ncseonline.org/nle/crsreports/03Feb/RL31530.pdf 


29 

Since 2001, chemical plant security has been subject to heightened scrutiny. A number 

of attempts have been made to address these issues and increase plant security. Given 

the large number of facilities, and the costs of increasing regulations, securing these 

facilities and decreasing the threat has been challenging...and has not yet been 

accomplished. 





Slide 30 



Not Just Fixed Facilities 


30 

A fixed facility is an industrial building, yard, or storage tank. 

Chemical incidents occur regularly. The vast majority of these have been accidental. 

Few have been from industrial sabotage, and successful chemical releases by terrorists 

remain very few. 

This slide shows that the number of incidents is quite high, upwards of 60,000 during the 

period studied (1987- 1996). Of concern, about ½ of these incidents involved 

transportation incidents and did not occur at fixed facilities. 





Slide 31 



Rail links transporting chemical tanker 

cars travel through or near major cities 

 


31 

This is a photo taken of a tanker car containing chlorine rolling through the nation’s 

capital in 2004. While attempts to change such vulnerable transportation routes have 

begun, as well as attempts to shift production to less toxic chlorine alternatives such as 

hypochlorites, a tanker spill by direct hostile action or otherwise remains a major 

concern. Chlorine tankers no longer travel on this rail line in D.C. However, other 

jurisdictions have not enacted similar legislation. 





Slide 32 



Railway Explosion 

• Power cables touch rail cars loaded with ammonium nitrate fertil izer 

• Buildings for several hundred meters were totally flattened 

• 129 public buildings destroyed or damaged including hospital, fo od processing 

plant, and college. 

• Rescue workers described utter devastation with damage extending for 4 km 


32 

Explosive chemical are of great concern. This event in North Korea in 2004 provides a 

graphic picture. In this case, power cables ignited a nitrogen-based (ammonium nitrate) 

fertilizer in the rail cars. The force of the explosion destroyed building for several 

kilometers. The death toll in this event was 154. 

In the middle of the right hand third of the pre-explosion image is a school, which was 

just letting out at the time of the explosion. Of the 154 deaths there were 76 children. 





Slide 33 



Area Before Explosion 


33 

This slide is an aerial view of the explosion site before the explosion. 





Slide 34 



Area After Explosion 


34 

This slide is an aerial view of the identical site after the explosion. 





Slide 35 



North Korean Railway Incident 

• Death toll: 154, including 76 schoolchildren 

– A primary school had just ended when the explosion 

happened 

– Some children were on their way home, while others were 

trapped in the building 

– Most people were injured when they were trapped or 

thrown from buildings. 


35 

The death toll in this even was 154, including 76 children. School had just let out, and 

some of the children were already outside, and some of the children were trapped in the 

school building. 





Slide 36 



School After Explosion 


36 

In this aerial view you see the school in approximately the middle of the image. 





Slide 37 



Prioritizing Chemicals of Concern: NATO 

ITF-25 Definition of TICs – 1996 

• High Production Volume Chemicals ( HPVs) 

– produced in quantities > 30 tons (60,000 pounds) in a single fac ility 

• High Toxicity 

– LCt50 by inhalation < 100,000 mg/min/M3 

• Appreciable vapor pressure at 20 °C 

– Thus, airborne hazards only 

• Hazard Index = {(toxicity)x(state)x(distribution)x(producers)} 

– maximum value of 625 


37 

How do we begin to prioritize among the hundreds of thousands of chemicals or 

chemical classes to determine which ones should receive our immediate attention and 

action 

One of the first attempts to come up with a prioritization list was undertaken by NATO 

(North Atlantic Treaty Organization) in 1996. Known as the NATO ITF-25 (International 

Task Force), this group performed a Hazard Vulnerability Assessment prioritizing 

chemicals based on their production volume of >30 tons per year in a single facility and 

their inherent toxicity based on an LCt50 of < 100,000. This served as the original 

definition of a TIC. 

Those that met these criteria were then further investigated based on their Hazard Index 

(HI), which itself was based on four factors. These factors were global extent of 

distribution, number of producers, inherent toxicity, and physical state (see Instructor 

Note for details) 

Toxicity is determined here as the concentration that kills 50% of animals (and 

extrapolated to humans). If the LCt50(LD50 in mg/m 3 x time in min) is less than 100,000 

it is considered in this formula to be highly toxic. The lower the LCt50, the more toxic the 

agent, since a lower dose is lethal. 





Slide 38 



NATO ITF-25: High Hazard TICs 

• Tissue Irritants 

– ammonia 

– boron trichloride 

– chlorine 

– fluorine 

– formaldehyde 

– hydrogen bromide 

– hydrogen chloride 

– phosgene 

– phosphorus trichloride 

– nitric acid 

– sulfur dioxide 

– sulfuric acid 


• Systemic Poisons 

– arsine 

– boron trifluoride 

– carbon disulfide 

– cyanide 

– diborane 

– ethylene oxide 

– hydrogen fluoride 

– hydrogen sulfide 

– tungsten hexafluoride 

38 

The NATO group came up with a list of 25 chemicals which they believed posed the 

highest hazard. The exact ranking of the chemicals are not important (and thus in 

alphabetical order). Note that many of these compounds are ones with which emergency 

responders have some familiarity (such as ammonia or chlorine). These TICs can be 

somewhat artificially divided into two groups: tissue irritants and systemic poisons. 

The list of tissue irritants is on the left. All produce upper and lower airway (throat and 

lung) irritation. There are no antidotes for this type of poisoning, and meticulous 

supportive care to prevent further lung injury is critical to survival. The evaluation, 

management and treatment is, for the most part, similar regardless of the specific irritant 

inhalant. 

We are able to respond initially to large scale incidents based on the symptoms 

displayed by people who have been exposed without necessarily knowing exactly which 

chemical is involved – knowing and finding out as soon as possible is still important! 

The systemic poisons are on the right. They are a more heterogeneous group of 

chemicals. Some like cyanide, are specific cellular asphyxiants, and this has a specific 

antidote about which you will hear more about later today in the Cyanide and Fumigant 

module. Another systemic poison of interest to toxicologists is hydrogen fluoride. 





Slide 39 



USACHPPM – 2002 Reevaluation 

• Also evaluated - corrosiveness, reactivity, 

flammability, less volatile chemicals 


39 

In 2002, the USACHPPM (U.S. Army Center for Health Promotion and Preventive 

Medicine) group undertook a reassessment of the earlier NATO prioritization. Other lists 

(that appear in this complex Venn diagram) were also studied, and the chemicals of 

concern were expanded to include less volatile chemicals as well as chemicals that were 

inherently reactive and flammable. 

It is easy to become overwhelmed by the thousands of chemical that exist. The process 

of prioritization and the prioritization lists that were produced help us as first responders 

to understand those that are most important and concerning. 





Slide 40 



Risk Assessment 

CHEMICAL 

HAZARD 

PROBABILITY 

RISK 

Hydrogen Cyanide 

Catastrophic 

Occasional 

High 

Sulfuric Acid 

Catastrophic 

Likely 

Extreme 

Acetylene 

Catastrophic 

Frequent 

Extreme 

Nitromethane 

Catastrophic 

Seldom 

High 

Phosgene 

Critical 

Occasional 

High 

Methanol 

Critical 

Occasional 

High 


40 

This table from the 2002 USACHPPM exercise, provides a sampling of chemicals that 

underwent this assessment and which ultimately received a risk ranking of high or 

extreme. Several of these such as hydrogen cyanide and phosgene will be discussed in 

much more detail later in this course. They color coded and used appropriate words to 

describe the hazard, discussed earlier, along with the probability of use (based on 

historical use, availability, etc) and from this calculated a “risk” of the use of an agent as 

a weapon. 





Slide 41 



Unusual but Easily Available Agents 


41 

Despite these lists, not all chemicals of concern for terroristic use are identified by these 

lists. There are many chemicals out there. Some of these are very unfamiliar to those of 

us not working directly with them or related industries. Some are in small volume 

production, and others just have not been considered. One example is osmium tetroxide, 

which is a very irritating chemical - corrosive to the eyes and lungs – used in NMR 

spectroscopy, a specialized analytical imaging technique. This was not on anyone’s 

“list” until a plot to use it was exposed. 





Slide 42 




42 

Accessibility is a key concept when it comes to how vulnerable we may be with regard to 

chemical X and chemical Y. Military warfare chemicals such as sarin or tabun are tightly 

secured by the military. While we may be concerned that a rogue State or large and 

well-financed terrorist enterprise may attempt to produce these extremely toxic warfare 

chemicals, their inaccessibility to most people makes their likelihood of use (particularly 

as an Agent of Opportunity) somewhat more remote. 

However, Osmium tetroxide, as seen in this example - and probably also discovered by 

the British terrorists - is sold by chemical supplies companies (sold at the time of the this 

episode). 





Slide 43 



Osmium Tetroxide 


43 

And, as you can see, OT is fairly inexpensive in the quantities use for NMR 

spectroscopy. A single gram could be purchased for $35, and is further discounted if 

you buy in bulk. 





Slide 44 




Which of the following is not a component of a hazard 

score or ranking 

1. Toxicity of a chemical 

2. Amount of a chemical on site 

3. Volatility of chemical 

4. Wind direction at time of release 

5. History of use in prior terrorist event 


44 





Slide 45 



Chemical Agents Employed by Terrorists 

• Corrosives - Acid / alkalis 

• Metals 

• Cyanide 

• Rodenticides 

• Pesticides 

• Poison gas 

Monterey Institute Database, 2002 


45 

It is important to study history. In the ongoing database of information maintained by the 

Monterey Institute in California, the agents that have actually been used were classified 

into several general categories. Some of the agents that have actually been employed 

including corrosives, metals, cyanide, pesticides, and poison gas. These chemicals will 

be discussed in much greater detail later throughout the day. 





Slide 46 



“Terrorists can make the 'unlikely' happen. ” 


46 

The premise of today's discussion is that we need to prepare for the unlikely and the 

unknown. We need to think outside the box. Today we take crashing planes into 

buildings as a threat that we need to plan against. Prior to 9-11, the plan for responding 

to hijacked airplanes did not generally focus on this outcome. 

Similarly, there have been many anthrax hoaxes delivered through the mail since the 

mid 1990s. The likelihood of a true anthrax attack via the mail was thought to be 

remote, given the premise that “weaponized” anthrax would not be efficiently 

disseminated by mail transport. The events of 2001 and 2002 demonstrated those 

beliefs to be wrong. 





Slide 47 



Methods Used by Terrorists for 

Delivery of Chemical (N=126) 

• Casual/direct contact 33 (30%) 

• Aerosol/spray 21 (19%) 

• Food/drink 13 (12%) 

• Unknown 12 (11%) 

• Product tampering 10 (9%) 

• Explosive 6 (5%) 

• Water supply 5 (4%) 

• Jug/jar/canister 1 (1%) 

• Mail/letter 4 (3%) 

• Reaction device 3 (2%) 

• Injection/projectile 1 (1%) 


Monterey Institute Database, 2000 

47 

Further data can be obtained from the Monterey Institute Database in 2000. It provides 

information on methods used by terrorists to inflict harm using chemical agents. As you 

can see a variety of delivery methods have been employed including direct contact, 

aerosols, product tampering, and injection devices. 





Slide 48 



Terrorism Preparedness 


48 

At the same time, our response to a chemical terrorist event is based on what we do 

every day in responding to individual illness and injury and HazMat events. This course 

will help by providing a framework to prepare for and respond to the “extra” threat. 

The difference between an “everyday” chemical event and a terrorist event is 

represented by the NBC Delta (NBC means nuclear, biological, chemical and generally 

means “all hazards”, although others use CBRNE to encompass explosives and to 

differentiate). In other words, each person in the lower half of the pyramid has a role in 

day to day response and this is learned during their existing preparedness training. 





Slide 49 



Unusual Agents of Historic Importance 


49 

This course will address a number of toxins of historic importance. As we prepare for the 

future and ponder the new and unthinkable, we also need to heed the lessons of the 

past. 

Ricin, actually militarized in the past, had the notoriety of being extremely potent and 

toxic at a very small dose. Its actual use had been limited to cold war spy intrigues and 

U.S. militia groups planning. Hence the surprise of finding ricin in the Senate Office 

building in 2004. Its notoriety was clearly also known to terrorists and would-be terrorists. 

If nothing else, the discovery of ricin spread fear and uncertainty. 

Ricin is what is left over in the water-soluble “cake” after castor beans have the castor oil 

expressed by a cold press process. 

Ricin was found Feb 3, 2004 on an automatic mail sorter in a mailroom in the Dirksen 

Senate Office Building. This closed several Senate offices for a few weeks for 

decontamination. 





Slide 50 




50 

In 2004, a recipe for ricin was found in a London apartment occupied by would-be 

terrorists. In this case the ricin had not been used, and no one had become ill, but its 

discovery gave further credence to terrorists interest in this deadly substance. 





Slide 51 



Unusual Agents: Characteristic Toxidromes 


51 

There are other agents that have been used that are considered highly unusual chemical 

poisons, but their clinical effects are largely unmistakable. We will cover this poison – a 

chlorinated hydrocarbon – and its effects on Victor Yushenko, Ukrainian prime minister, 

in more detail later in the day. 





Slide 52 

One such incident occurred in 1989 when it was alleged that Chilean grapes imported to 

the U.S. were deliberately contaminated with cyanide. In fact, an initial laboratory 

analysis one of these grapes we positive for a cyanide. This lab result turned out to be a 

false positive, and in fact, there was no cyanide contamination. In the meantime, the 

Chilean grape crop destined for import to the U.S. had to be destroyed at the cost of a 

loss of $100s of millions. 

No one died, no one was medically harmed, and in fact no one was contaminated, but 

the impact was still profound. 





Slide 53 



Challenges of Chemical Agent 

Identification 

• Symptoms similar to common disease (gastroenteritis) 

• Immediate symptoms might be mild or nonexistent 

• Staggered reports over long periods / different locations 

• Mixed clinical presentations 

• Health care providers may be less familiar with certain 

chemical induced presentations 

MMWR 10/3/03 


53 

Given large variety of potential agents and often non-specific initial presentations, we 

need to look for additional clues to suspect the use of TICs/TIMs. 

Some of the clinical pearls appear on this slide. While some chemicals cause a typical 

toxidrome, more often the clinical presentation may not be diagnostic of any specific 

chemical agent. Often the symptoms are gastrointestinal in nature. At times the 

immediate symptoms might be mild or non-existent. Given the delay in some of these 

cases, we have devoted an entire lecture later in the day to these delayed syndromes. 

Many health care providers may be less familiar with chemical induced presentations of 

patients since these cases are relatively uncommon. Medical toxicologists strive to stay 

current and maintain the most knowledge about these clinical findings because this is 

truly our area of specialization. Other physicians may rarely if ever encountered some of 

these problems. 





Slide 54 



Clues to Chemical Exposure 

• Unusual number seeking care for chemical -related 

illness 

• Unexplained deaths among young, healthy people, 

plants, animals 

• Clusters of illness with common source (e.g. water) 

– Surveillance methods including PCC, pharmacy sales 

• Presence of a clinical pattern or toxidrome 


54 

There are some key clues that may lead one to suspect a possible chemical exposure. 

These include patterns where an unusually large number of patients seeking care for 

possible chemically related illnesses, unexplained deaths among people, animals or 

plants, and or the presence of a particular clinical pattern or toxidrome. Some of our 

surveillance efforts are directed at early identification of these clues. These utilize 

multiple resources including poison control centers (PCC) and pharmacy sales numbers 

of items like nonprescription cold medications. 

A toxidrome is a “toxicologic syndrome” which is a collection of clinical findings that 

suggest as specific etiology and treatment. An example for this lecture series would be 

the opioid toxidrome, discussed in the Neurotoxic syndromes talk. In this syndrome the 

finding of depressed mental status, respiratory depression, and miosis (small pupils) 

suggests the diagnosis and the therapy (ventilatory support and naloxone). 





Slide 55 



Selected Toxidromes and Potential 

Chemical Etiologies 

Category 

Severe gastroenteritis 

Cholinergic crisis 

Cellular hypoxia 

Peripheral neuropathy 

Mouth pain / ulcerations 

MMWR 10/3/03 

Clinical Syndrome 

Abdominal pain, emesis 

profuse diarrhea, shock 

SLUDGE symptoms, 

Fasciculations, weakness 

N/V, headache, AMS, shock, 

seizures, dec pH 

Muscle weakness, sensory 

loss 

Lip / mouth / pharyngeal 

ulcerations; burning pain 

Potential Chemical 

Etiology 

Arsenic, Ricin, Colchicine 

OP insecticides, nicotine 

CN, SMFA, CO, Azide 

Hg, As, Thallium, Lead, 

Paraquat / diquat; caustics, 

Hg 


55 

Some chemicals cause a characteristic clinical syndrome. These syndromes (or 

toxidromes) have symptoms/signs that are typical for that particular type of chemical 

exposure. Some of these toxidromes include severe gastroenteritis, cholinergic crisis, 

cellular hypoxia, neuropathy and mouth ulcerations. As you can see, a number of 

chemicals can cause each toxidrome with the syndrome depicted on the slide. It is also 

important to realize that these are the textbook descriptions and not all patients follow 

the textbook script to the letter. These descriptions serve as guides and are not definitive 

confirmation of a cause, particularly given the use of unusual agents. 





Slide 56 



A Case 

49 yo man suddenly develops leg pain while walking 

• Day 1 - fever, nausea, vomiting 

• Day 2 - tachycardia, lymph node swelling and shock 

• Day 3 - kidney failure, vomited blood, heart block 

• Day 4 - death 

• Presumed Cause of Death – Septic Shock 


56 

Let’s review a famous case of chemical terrorism. This only involved a single individual, 

and may be better called an assassination; it caused quite a sensation at the time. 

A 49 yo man in London suddenly develops right thigh pain while walking 

Day 1 - fever, nausea, vomiting 

Day 2 – tachycardia (fast heart beat), lymph node swelling and shock 

Day 3 - kidney failure, vomited blood, heart block (abnormal heart rhythm) 

Day 4 - death 

Presumed Cause of Death – Septic Shock (low blood pressure due to overwhelming infection) 





Slide 57 



Selected Toxidromes and Potential 

Chemical Etiologies 

Category 

Severe gastroenteritis 

Cholinergic crisis 

Cellular hypoxia 

Peripheral neuropathy 

Mouth pain / ulcerations 

MMWR 10/3/03 

Clinical Syndrome 

Abdominal pain, emesis 

profuse diarrhea, shock 

SLUDGE symptoms, 

Fasciculations, weakness 

N/V, headache, AMS, shock, 

seizures, dec pH 

Muscle weakness, sensory 

loss 

Lip / mouth / pharyngeal 

ulcerations; burning pain 

Potential Chemical 

Etiology 

Arsenic, Ricin, Colchicine 

OP insecticides, nicotine 

CN, SMFA, CO, Azide 

Hg, As, Thallium, Lead, 

Paraquat / diquat; caustics, 

Hg 


57 

Note that using the guide provided by the CDC leads to the suspicion of one of the 

cellular poisons, ricin, colchicine or arsenic because he had severe gastroenteritis and a 

shock presentation. 





Slide 58 



Ricin Poisoning 


58 

In fact on autopsy a tiny metallic sphere was retrieved from his posterior thigh. Pictured 

above, the sphere was ingeniously introduced through the tip of a specialized umbrella 

designed to implant such a metallic object. It was only later when there was a 2 nd case, 

that the mystery was solved and it became apparent the this dissident Bulgarian 

journalist (Georgi Markov) had died after have been injected with the metallic sphere 

which contained… ricin…derived from the castor bean plant. 

The modified umbrella is on the left. The metallic object with two tiny holes drilled 

through it, with a total volume of 0.2 microliters. The plant on the right is Ricinus 

communis, or the Castor Bean plant. The seeds come from the reddish pods, which are 

found in the autumn. 





Slide 59 



QUESTIONS 


59 

How real is the threat 

We need to be aware of TICs and TIMs and prepare for – or better yet – prevent their 

use as chemical weapons. To do this, at whatever level of preparation and response we 

are involved in, we can utilize the framework of historic examples, regional hazard 

vulnerability assessment and response, and clinical recognition of patterns consistent 

with various chemical classes. 





Module One Summary 

This module provided a comprehensive introduction and overview of the Chemical Agents of 

Opportunity for Terrorism: The Medical and Psychological Consequences of TICs (Toxic 

Industrial Chemicals) and TIMs (Toxic Industrial Materials) course, sponsored by The American 

College of Medical Toxicology (ACMT). It presented a broad overview of the numerous 

potential toxic industrial chemicals and toxic metals readily available in our society, along with 

the most likely scenarios that might occur as the result of the intentional release of the agents 

by terrorists. The intentions of such a terrorist attack as critical analysis reveals, is to cause 

illness and injury and potentially large numbers of casualties but more over, to create social 

panic and chaos and substantial demands on our health care system’s ability to respond. 

Historical examples of major chemical events and the resultant pertinent legislation that was 

implemented in response to these occurrences governing the production, transportation, and 

storage of toxic chemicals were reviewed. A framework for first responders and first receivers 

for the early detection and recognition of toxic chemicals is provided in order to optimally 

prepare, identify and defend against chemical threats. 

Seeking to provide awareness-level training across several disciplines on a variety of toxic 

syndromes likely to be encountered following exposures to TICs and TIMs and other chemical 

agents of opportunity, this module introduced the concept of dose-response, the health 

implications resulting from the release of TICs and TIMS, it identified multiple sources available 

to obtain common industrial chemicals and the potential scenarios that might result from the 

use of these chemical agents by terrorists. 

First responders and first receivers are provided with a framework to enhance understanding 

and recognition of the common health effects of apparently disparate chemical toxins, and 

current and reliable information regarding current policy and public health management 

strategies. 





Module Two 

The Clinical Neurotoxicology of Chemical Terrorism - 

Administration Page 

The underlying neurophysiology of the brain makes it a likely target for terrorism. Interruption of 

the normal role of neurotransmitters in the brain will alter functionality and render the individual 

incapable of ‘fight or flight’. Because the potential exists for neurotoxins to be used in a terrorist 

attack it is imperative that clinicians and first responders are able to recognize the common toxic 

syndromes that affect the nervous system, including sedation, convulsions and hallucinations. 

Duration 

45 minutes 


This module provides a detailed overview of the major toxic syndromes along with examples of 

chemical agents of opportunity for each clinical syndrome. Case studies are presented that 

highlight the historical use of these agents in terrorist attacks. Potential antidotes, initial 

treatment strategies and management of each clinical syndrome are reviewed. 


• Recognize the common toxic syndromes that affect the nervous 

system, including sedation, convulsions and hallucinogens. 


Resources 

• Describe the role of neurotransmitters in brain function. 

• List examples of agents of opportunity for each clinical syndrome. 

• Describe initial treatment strategies for each clinical syndrome. 

• Identify antidotes where appropriate. 







1:8 (minimum) to 1:25 (maximum) 


1. Burns MJ, Linden CH, Graudins A, et al. A comparison of 

physostigmine and benzodiazepines for the treatment of 

anticholinergic poisoning. Ann Emerg Med 2001;37(2):239-41. 






2. Centers for Disease Control and Prevention (CDC). Nicotine 

poisoning after ingestion of contaminated ground beef –Michigan, 

2003. MMWR May 9, 2003;52(18):413-16. 

3. Centers for Disease Control and Prevention (CDC). Poisoning by an 

illegally imported Chinese rodenticide containing 

tetramethylenedisulfotetramine--New York City, 2002. MMWR Morb 

Mortal Wkly Rep. 2003 Mar 14;52(10):199-201. 

4. Hoffman JR et al. The empiric use of naloxone in patients with altered 

mental status: a reappraisal. Ann Emerg Med 1991;20:246-52. 

5. Lakoski JM, et al. The advantages and limitations of calmatives for 

use as a non-lethal technique. 

nldt2.arl.psu.edu/documents/calamative_report.pdf 

6. McCarron MM et al. Acute phencyclidine intoxication: clinical patterns, 

complications and treatment. Ann Emerg Med 1981;6:290-7. 

7. Wax PM, et al. Unexpected "gas" casualties in Moscow: a medical 

toxicology perspective. Ann Emerg Med 2003;41:700-5. 


















Module Two 

Icon Map 






instruction 





Slide 1 


Module Two 

The Clinical Neurotoxicology of Chemical 

Terrorism 


1 

This module is the Clinical Neurotoxicology of Chemical Terrorism. 

Neurotoxicology is the study of toxins and other chemical on the nervous system. 

Clinical refers to the medical effects observed in people. 





Slide 2 

Due to its complexity and the ease of disrupting its function, the human brain makes a 

great target for terrorism. The thought of someone interfering with our ability to function 

is very disturbing and highlights the power of the psychological effects of terrorism. The 

Central Nervous System is central to both our functionality and our thinking. 

Central nervous system is the organ system that includes the brain and spinal cord. Our 

ability to think, react and the control of many bodily functions are all coordinated by the 

brain. Disruption of brain function can be quite disabling and lead to all sorts of mental 

and psychological problems. 





Slide 3 

Despite its complexity, the brain really only displays its dysfunction in a small number of 

ways. There are basically three toxic syndromes that affect the central nervous system. 

This includes CNS depression (sedation), CNS excitation (seizure) and possibly altered 

thoughts, as with hallucinations. 

The objectives for today’s presentation include: 

o Review of the unique clinical effects of toxins that result in sedation syndromes 

o 

o 

List examples of agents of opportunity for each syndrome 

Describe the initial treatment strategy for each category of agent 

A syndrome refers to a constellation or grouping of signs and symptoms. A toxic 

syndrome refers to the signs and symptoms associated with exposure to a specific toxin 

or chemical. There are several different types of toxic syndromes. The three toxic 

syndromes which are most commonly seen are those that cause sedation or sleepiness, 

convulsion which are often referred to as seizures and hallucinations, which are 

distortions of reality. It is important to recognize that convulsions is an extreme 

manifestation of overstimulation, which is the opposite of sedation. People who have 

hallucinations may be awake and even alert but are not thinking clearly. A patient with 

hallucinations is often neither sedated nor agitated but they are clearly altered. 





Slide 4 



The Balance of the Brain 

• The brain is a fine balance of excitatory and inhibitory 

influences 

– Slight alterations in either direction are significant 

Excitation 

Glutamate 

Catecholamines 

Inhibition 

Gamma-aminobutyric acid 

(GABA) 

Module Two - The Clinical Neurotoxicology of Chemical Terrorism 

4 

The normal state of the brain is maintained by balancing both excitation and inhibition, 

each mediated by a unique set of chemicals called neurotransmitters. We alter our 

neurotransmitters under normal conditions to suit our needs. For example, in order to 

sleep, you need to increase inhibition and reduce excitation. 

Neurotransmitters are chemicals in the nervous system including the brain that transmit 

information from one neuron to the next (neurons are cells found in the nervous system 

and brain). There are a number of different types of neurotransmitters. These include 

adrenaline also known as epinephrine which belongs to the neurotransmitter class 

known as catecholamines. Some neurotransmitters cause stimulation and others cause 

inhibition or sedation. Catecholamines cause stimulation. Another neurotransmitter 

that causes stimulation is glutamate. An example of a neurotransmitter that causes 

inhibition is gamma-aminobutryic acid. This long chemical name is often abbreviated as 

GABA. 

The see-saw in the slide represents the delicate balance in the brain between excitation 

and inhibition. A person with a normal mental status is someone for whom these 

influences are in balance, while disorders are characterized by a tilt in favor of too much 

excitation (or too little inhibition) or too much inhibition.(or too little excitation). 





Slide 5 



The Balance of the Brain 

• In addition, other neurotransmitters influence our 

mood, our ability to think, remember, etc. 

Excitation 

Inhibition 

Modulators of Thought Processes 

Serotonin 

Acetylcholine 


5 

Other neurotransmitters play a role in our functional abilities, or our ability to process 

information smoothly. For example, Serotonin and Acetylcholine serve as modulators of 

our thought processes. 

Some neurotransmitters do not excite and do not sedate (brain inhibition) but cause an 

alteration in thinking and mood. Two examples of neurotransmitters that may alter mood 

or thought are serotonin and acetylcholine. An increase or decrease in the amount of 

these neurotransmitters may have a significant impact on mood and thought. 





Slide 6 



Clinical Syndromes of the CNS 

Too much inhibition = Sedation/coma 

Excitation Inhibition 


6 

Chemicals (drugs) typically cause sedation or coma by enhancing our inhibitory tone, not 

by reducing excitation. 

Too much inhibition causes sedation. A person who is sedated is not alert. They are 

usually sleepy and may be difficult to arouse. With increasing sedation patients may be 

comatose. This may be confused for sleeping but the typical person who is sleeping can 

usually be awoken with some sort of stimulation. The comatose patient can not be 

awoken. If this coma is caused by a drug or chemical, the patient may not awaken until 

the chemical leaves the body or wears off. In extreme cases someone who is comatose 

may slow down their breathing to such an extent that they are not longer getting enough 

oxygen. This may result in death and is a common cause of death after some drug 

overdoses. 





Slide 7 




Too much stimulation = Convulsions 

Excitation 

Inhibition 


7 

While chemicals (and drugs) may cause convulsions by enhancing excitation, a more 

common mechanism for intoxicant-induced convulsions is diminished inhibition (known 

as “inhibition of inhibition”). 

A convulsion occurs when the patient has repetitive and uncontrolled jerking of the 

extremities. This is sometimes referred to as a seizure. However, a seizure refers to 

abnormal electrical activity in the brain, while convulsions refer to the abnormal muscle 

activity we are able to observe. Not all convulsions are seizures – the best example 

being the effects of strychnine, where the patient is awake and aware, but unable to 

control his muscle movements. Convulsions are often violent and may result in injury to 

the patient. In addition the intense muscle activity may result in an elevated body 

temperature and muscle damage. Prolonged seizures (those lasting more than 30 

minutes) or repetitive seizures without recovery of consciousness are termed status 

seizures. These can cause permanent brain injury and can lead to death. 

Patients having seizure are often unaware of their movements and may not even be 

aware that they are having a seizure. Prior to the onset of convulsions the patient may 

exhibit tremors and jitteriness. There are many different causes of seizures. Epilepsy is 

one of the most common causes. Epilepsy is not caused by specific drugs or toxins and 

usually develops in childhood. There are a large number of drugs and toxins that can 

also cause seizures. 

Note the see-saw is tilted towards excitation. The boxes depict both increased excitation 

and decreased inhibition (compared to baseline). 





Slide 8 




Altered Modulation of Thoughts = Hallucinations 


8 

Alterations in the smooth flow of information in our brain results in hallucinations. 

Sensory input is unfiltered resulting in sensory overload and altered modulation of our 

thoughts, causing hallucinations and delirium. 

Hallucinations are false perceptions that have no basis in the external environment. 

There are several different types of hallucinations. These include auditory hallucinations 

where one hears voices which are not present. Another type of hallucination is visual. 

People who experience visual hallucinations are seeing people or objects that are not 

present. Someone who is having hallucinations may not think clearly. For example, it 

would be very dangerous to drive a car or operate machinery at the same time one was 

experiencing hallucinations. A soldier on the battlefield might become ineffective and 

even dangerous to colleagues if he or she was experiencing hallucinations. 

The see-saw depicts wavy lines with upended boxes reflecting the altered thought 

process. 





Slide 9 



Clinical Syndrome: Sedation 



9 

Let’s talk about sedatives and their potential for use by terrorists. 

Recall that sedatives are going to enhance our inhibitory tone. 





Slide 10 



• Dose-Response 

Ethanol Intoxication: 

A Prototype for Calmatives 

– The more you drink, the drunker you get 

– 1 beer: buzz 

– 2 beers: intoxicated 

– 6 beers: uncoordinated, slurred speech, 

• Disinhibited 

– 24 beers: coma, respiratory arrest 


10 

The term calmative refers to a drug or chemical that producing a calming state. Ethanol 

represents a nice example of a calmative and reinforces a key concept in toxicology - 

dose response. The greater the exposure the more effect you see. For example, as you 

drink more bottles of beer, the neurologic effects progress from mild inebriation to coma. 

A larger dose or amount of a calmative may produce sedation, and an even larger dose 

may produce coma. There are a large number of drugs and chemicals that cause 

calming and sedation. One of the most commonly used chemicals that cause these 

symptoms is alcohol. The specific chemical name of the active ingredient in alcohol is 

ethanol. Different people have different responses to drinking the same amount of 

ethanol. If someone doesn’t drink and then drinks one or two beers they may become 

intoxicated while others who drink many beers every day may not experience any 

obvious effect after only drinking one or two beers. However, for both individuals, if they 

drink enough they will develop more and more “inhibitory” effects. Eventually the patient 

who drinks a large number of beers may develop respiratory depression which is a 

decreased number of breaths each minute. Normal is about 12 to 20 breaths per 

minute. A respiratory arrest occurs when the number of breaths approaches no breaths 

per minute. 





Slide 11 



Case Study: Moscow Theatre Hostage 

Crisis (2002) 


11 

Let’s look at an example of a mass poisoning using a calmative agent. The Moscow 

theater hostage crisis was the seizure of a crowded Moscow theatre on October 23, 

2002 by about 40 armed Chechen militants who claimed allegiance to the separatist 

movement in Chechnya. They took 850 hostages and demanded the withdrawal of 

Russian forces from Chechnya and an end to the Second Chechen War. 





Slide 12 




Crisis (2002) 


12 

This is a photo of the ambulances that lined up outside the theatre awaiting casualties 

from the hostage takeover and the subsequent Russian military reentry into the theatre. 

Pandemonium resulted- panic and social disruption are among terrorism’s goals. 





Slide 13 




Crisis (2002) 

• Russian Federal Security Service pumped 

unidentified “gas” into building 

• Security forces raided building 

• 128 of 800 (16%) hostages died 

– All but one from gas 

• All 42 separatists died 

– 39-41 from gas 


13 

After a 2 ½ day siege, Russian security services pumped an unidentified chemical agent 

into the building's ventilation system and raided it. Officially, 39 of the terrorists were 

killed by Russian forces; at least 128 of the hostages died. Some estimates have put the 

civilian death toll at more than 200. 





Slide 14 



What happened 


These images reveal how much confusion there was. Some victims were alive and 

appear well, others appear quite ill. The degree of Personal Protective Equipment use 

varied, but appears to have been inadequate in most images. 

14 





Slide 15 




15 

The events in the news media unfolded over several days. It was initially thought that the 

security services pumped an aerosol anesthetic into the theatre - later reported to be 

weaponized Fentanyl (possibly carfentanil) - through the air conditioning system. If it was 

an opioid, why was the military not prepared with antidote (naloxone)….would it have 

worked or helped anyway The amount of time to enter the building and administer the 

antidote naloxone makes it unlikely to have helped many. 

An opioid is a type of drug class that includes heroin and morphine. The drugs present 

in the poppy plant are termed opiates. There are other drugs that are synthesized or 

manufactured in pharmaceutical factories that resemble the active ingredients found in 

the poppy plants. These are referred to as synthetic opioids. Examples include 

meperidine and methadone. Another example is fentanyl which is very potent as will be 

described on the next slide. 

Opioids cause sedation, and in larger doses cause coma. They are also used to control 

pain. Deaths occur from respiratory arrest. 





Slide 16 



Characteristics of Opioids 

Agent Potency 

(vs. morphine) 

Morphine 1 

Meperidine 0.5 

Methadone 4 

Fentanyl 300 

Sufentanil 4500 

Alfentanil 75 

Remifentani 220 

lCarfentanil 10,000 

Wax PM, Becker CE, Curry SC. Ann Emerg Med 2003;41:700 -5. 


16 

Fentanyl has a very high potency, which means it is effective in very small (microgram) 

doses. Carfentanil is even more potent and would make an effective weapon if put into a 

respirable form (e.g., aerosol). There are some suggestions that carfentanil was in fact 

the implicated toxin. 

This slide lists a number of chemicals or drugs which belong to the opioid class. They 

are all used medically except for carfentanil which is used as a veterinary anesthetic in 

large animals. The potency refers to how strong the drug is compared to another drug. 

The more potent a drug, the greater the effect at the same dose. A drug that has 10,000 

times the potency of another drug is essentially 10,000 times stronger at the same dose. 

Hence, to produce a similar effect one would give a much, much smaller dose of the 

more potent drug. 





Slide 17 




17 

Carfentanil is available as a large animal tranquilizer (for Moose or elk) sold under the 

brand name of “Wildnil”. 





Slide 18 



Positive Purpose 

“The use of pharmacological agents 

to produce calm behavioral state , 

particularly as relevant to 

management of individuals and/or 

groups that are agitated, 

aggressive and/or violent, is a 

topic with high relevance to 

achieving the mission of law 

enforcement and military 

communities ” 

(nldt2.arl.psu.edu/documents/calamative_report.pdf ) 

October 3, 2000 


18 

Sedatives can be put to positive use to overcome an aggressive person or group, the 

difference being the route of delivery. In the emergency department (ED) we frequently 

sedate people in order to produce a calm behavioral state. To sedate a group, the 

chemical sedative must be delivered in a different fashion, such as by inhalation. This 

has been studied, along with other techniques such as sticky foam and netting, as a 

non-lethal technique to replace bullets for law enforcement. 





Slide 19 



Inhaled Calmatives/Sedatives 

• Aerosolized drugs 

– GABAergic agents 

• Benzodiazepine (e.g. diazepam) 

• Barbiturate (e.g. pentobarbital) 

– Opioids 

• Volatile agents 

– Hydrocarbons 


19 

This slide describes some other examples of agents that would be useful as calmatives. 

They are all used in clinical medicine given their relative effectiveness and safety. 

Effective delivery is the challenge. Some hydrocarbons can be readily converted to 

gaseous form (such as inhalational anesthetics (halothane)) while most drugs are solids 

that, once dissolved in water or another solvent, can be aerosolized (misted). However, 

even creating a respirable aerosol is quite difficult and requires sophisticated technology. 

Not all substances that are inhaled are true gases. Some chemicals are liquid particles 

that can be suspended in air. This appears as a fine mist. The process of producing 

this mist is known as aerosolization. This mist preparation may also be known as an 

aerosol. Some liquid chemicals that are calmatives or sedatives have been aerosolized 

for use. These include agents that act through the GABA neurotransmitters discussed 

previously. These agents cause sedation. Examples are two drug classes known as 

benzodiazepines and barbiturates. While one would not necessarily use aerosolized 

versions of these drugs to treat patients, such aerosolized versions might have other 

uses such as to sedate large crowds of people, hence their potential use by law 

enforcement and the military. 

Volatility generally refers to the ability of a liquid to convert to a gas form (vapor) at 

relatively low temperatures. Unlike aerosols, vapors are not suspended liquid particles. 

Hydrocarbons refer to liquids which give off vapors at a high enough temperature. For 

instance, gasoline is a liquid hydrocarbon. An open can of gasoline emits a vapor which 

has a distinctive odor. Hydrocarbon vapors may also cause sedation. Drugs used in 

anesthesia that put patients to sleep in the operating room are hydrocarbons such as 

halothane (and in the past, ether and chloroform). 





Slide 20 



Calmatives/Sedatives 

• Suspect whenever clinical picture presents with predominant 

CNS depression 

– All produce dose dependent sedation 

• Major complication: RESPIRATORY DEPRESSION 

– Respiratory depressant effects vary 

• Specific Toxic Syndrome: CNS depression, pinpoint pupils, 

and respiratory depression = Opioid 


20 

The sedative toxidrome is characterized by dose-dependent sedation with relatively 

preserved respiratory effort. However, most central nervous system depressants are 

associated with some degree of respiratory depression at higher doses. Some, like the 

opioids, are associated with profound respiratory depression. This explains the high 

fatality rate in the Moscow theater. 

Respiratory depression, or a decrease number of breaths per minute, is the most serious 

problem associated with exposure to calmative or sedative agents. At high enough 

doses, this can result in a respiratory arrest and death. 

Opioids commonly cause respiratory depression. Toxicity from opioids also includes 

central nervous system depression and pinpoint pupils (also known as miosis). 





Slide 21 

The opioid toxidrome (toxicological syndrome) is relatively easy to recognize, particularly 

for medical personnel, since it is commonly noted in heroin users. Treatment involves 

administration of an antidote called naloxone (Narcan). 

The opioid toxidrome consists of central nervous system depression, respiratory 

depression and pinpoint pupils (miosis). Looking for and recognizing these findings on a 

physical examination is very important since people with this condition require 

emergency treatment. The failure to treat may result in a patient’s death. 

The treatment of choice is naloxone, also known by its trade name as Narcan®. This 

drug can be administered by the intravenous (IV) route (through a vein) or through an 

endotracheal tube if the patient is already intubated. The usual dose for naloxone is 0.4 

mg. It is usually pushed rapidly through the IV. Some patients may not respond to this 

first dose and will require more naloxone. Typically patients respond to 2 mg of 

naloxone although in some instances as much as 10 mg may be administered to reverse 

the effects of respiratory and CNS depression. 





Slide 22 

Naloxone works by blocking the effect of the opioid on its inhibitory receptor. It basically 

knocks the drug off the receptor and reduces the enhanced inhibition back to baseline. 

After administration patients wake up within seconds, and sometimes withdraw if they 

are chronic users (as with heroin)….not a terrorism issue. 

Realize that in many situations the toxic exposure results in toxicity that lasts longer than 

the antidote. Patient’s initial symptoms may then recur when the naloxone wears off. 

The use of naloxone REVERSES the inhibition that is caused by an opioid drug. The 

onset of action after IV administration of naloxone is fast and generally occurs within 1-2 

minutes. Its duration of action is 20 to 90 minutes. Naloxone reverses the effects of the 

entire family of opioid drugs including heroin, morphine, fentanyl, methadone, and 

hydrocodone. For some opioids such as methadone and hydrocodone the dose 

necessary to reverse the drug effects is greater than 2 mg. Upwards of 10 mg may 

sometimes be required is some of these cases. This reflects the relative potency of 

binding to the opioid receptors in the brain. 





Slide 23 

In some cases, simply providing ventilation is sufficient, and the administration of 

naloxone may not be necessary. The reason that opioids and most other sedatives kill is 

respiratory depression (assuming you are not driving a car or standing on the ledge of a 

cliff). Thus breathing for the person, either with mouth to mouth or by way of a bagvalve-mask 

as in the picture, is generally sufficient to save their life. Realize that you 

may have to ventilate for hours after exposure to some long acting sedative agents. 





Slide 24 





Slide 25 



Clinical Syndrome: Convulsions 



25 

The second clinical syndrome to discuss is convulsions/seizures. A seizure really refers 

to brain activity whereas convulsion is what you see when you look at the patient - that is 

the movement itself. Some convulsant toxins are not seizure inducing. An example is 

strychnine. 

These words – seizure and convulsion – are sometimes used interchangeably – but as 

noted before – a seizure refers to the abnormal electrical activity that occurs in the brain 

and is usually manifested by violent rhythmic movements of the extremities while 

convulsions only refer to these abnormal movements. Strychnine does not cause 

abnormal electrical activity in the brain. Strychnine only effects neural impulse 

transmission in the spinal cord which also happens to cause convulsive movements of 

the extremities. Hence strychnine poisoning causes convulsions without seizures. 

Robin Cook’s medical novel, Seizure, is used here just as a graphic depiction of a nerve 

synapse (nerve-to-nerve communication). 

The see-saw depicts a tilt towards the excitatory side. Note that the major reason for this 

imbalance is a decrease in inhibitory input. 





Slide 26 

In coma, enhancement of inhibition is the predominant cause of depressed mental 

status. In seizure/convulsion it is inhibition of inhibition that is most important. 

Remember that different neurotransmitters can either cause excitation (glutamate), or 

inhibition (GABA). Any change that tips the balance in favor of excitation can produce 

convulsions/seizures. This can occur by increasing excitatory neurotransmitters, or by 

decreasing the levels of inhibitory neurotransmitters. The most common toxin-induced 

seizures are triggered by decreasing the levels of inhibitory neurotransmitters. 





Slide 27 



Inhibition of inhibition 



27 

This slide depicts the information stated on the previous slide. Decreasing or inhibiting 

the inhibition (smaller inhibition box) leads to increased excitation (larger excitation box). 

The scale is tipped in the excitation direction. 





Slide 28 



MMWR 2003;52:199 -201 


28 

A report from NYC published in the CDC’s rapid turnaround journal (MMWR) discussed 

a case of a young girl in a Chinese immigrant family, who, in May 2002, developed 

status epilepticus unresponsive to conventional therapy after ingesting a powder from an 

apparent rodenticide packet marked with characters and purchased locally in Chinatown. 

At that time, despite intensive investigation, the nature of the powder could not be 

determined. 

A rodenticide is a chemical that is used to kill rodents such as rats and mice. These 

chemicals tend to be highly toxic. This slide depicts the rodenticide package in this case. 

The pictographs are easy to interpret as a rat or mouse poison, but the Chinese 

characters are not readily interpretable. Illegally imported foreign products can result in 

domestic exposures to unusual toxic chemicals, and health-care providers might not be 

able to provide appropriate therapy because the chemical ingredients might not be listed 

or recognized even after translation of the product label. 





Slide 29 




29 

Four months later, on September 14, 2002 a snack shop owner in China poisoned food 

in a competitor's snack shop with a rodenticide identified as Dushuqiang, resulting in 38 

deaths. Although it has been banned for sale since the mid-1980s, it was still widely 

available in China. Dushuqiang contains tetramine, sometimes known as TETS. TETS is 

a little-known, often unrecognized, and highly lethal neurotoxic rodenticide that once was 

used widely. 

Following news reports of this incident, the New York City Poison Control Center 

conducted additional laboratory testing of the product associated with the poisoning in 

New York City in May 2002 and confirmed TETS in the product. 

TETS is an odorless, tasteless, and water-soluble white crystalline powder that acts as a 

-amino butyric acid (GABA) antagonist (China Center for Disease Control and 

Prevention [CDC], unpublished data, 2002), TETS, like picrotoxin, binds 

noncompetitively and irreversibly to the GABA receptor on the neuronal cell membrane 

and blocks chloride channels. The most common routes of exposures are through 

ingestion and inhalation (China CDC, unpublished data, 2002). TETS is not registered 

by the U.S. Environmental Protection Agency for use in the United States, and its 

importation, manufacture, and use in the United States are illegal. 





Slide 30 



Tetramine 

• Du-shu-quiang (“very strong poison ”) 

• Used as a rodenticide in China 

– Banned in 1984 

• Like many substances used as rodenticides, 

tetramine is highly toxic to humans 


30 

This is the first known case of TETS poisoning in the United States. The chemical's 

morbidity and lethality and the lack of a known antidote present a danger to human 

health in areas where TETS might be imported illegally. Just as it was used to poison the 

rice in China, concern for use as a terrorist agent in the US is obvious. 

While the term tetramine is generally used to refer to this toxin it also refers to several 

nontoxic chemicals which can make the use of this term confusing. It causes 

convulsions and over-excitation which leads to the death of rodents which is the desired 

outcome; but unfortunately causes the same symptoms in humans. There are a wide 

variety of substances used as rodenticides and many of them act by causing over 

excitation, convulsions, and seizures. Strychnine is another example of a rodenticide 

that is highly toxic and causes convulsions. 





Slide 31 



Rat Poison 


31 

Tetramine has been reportedly used several times in epidemic poisoning in China. 





Slide 32 



Some Chemical Causes of Convulsions 

• Organophosphate & Carbamate Insecticides 

• Nicotine 

• Hydrazines 

• Camphor 

• Organochlorines 

• Strychnine 


32 

Other convulsant poisons that are relatively easy to access include the chemicals listed 

here. Nicotine was used by a supermarket clerk in Michigan to poison ground beef 

patties. Hydrazines are used as rocket propellants. Organophosphate and carbamate 

insecticides, camphor, organochlorines, and strychnine all are used as pesticides for 

different animal species. The use of any of these agents in an act of terrorism is a 

distinct possibility. 

Nicotine is widely available from tobacco and a variety of other nicotine-containing 

plants, ingestion can lead to severe vomiting and diarrhea, high blood pressure, anxiety, 

and a rapid heart rate. At high doses nicotine stimulates muscle spasm (twitching). 

After a period of stimulation the muscle can become fatigued and subsequently lead to 

muscle weakness or even paralysis. 

Hydrazines are compounds found within certain poisonous mushroom species and is a 

component of rocket fuel. Ingestion leads to seizures that are often resistant to standard 

anti-seizure therapy. It works by inhibiting the normal function of vitamin B-6 

(pyridoxine) in the brain.. 

Camphor is used in mothballs. In the United States camphor is limited to 11% of the 

mothball, however older mothballs or those from other countries can have very high 

concentrations of camphor. Ingestion of camphor can lead to early onset of seizures. 

Organochlorines are a wide variety of compounds which can have differing effects 

depending on the exact chemical. Many result in overexcitation and convulsions. A 

common treatment for scabies (a mite that burrows in the skin) is lindane, an 

organochlorine insecticide, that has caused seizure when ingested or over-applied to the 

skin. 

Strychnine is still found in rat poisons, and poisons for larger animals such as coyote. It 

prevents the normal relaxation of muscles. This leads to extremely painful convulsions 

that closely resemble seizures. It has no effect on the brain so victims are conscious 





during these severe episodes which are very painful and can lead to death from 

impairment of respiratory muscle function. 





Slide 33 



Convulsions: Management 

• Benzodiazepines 

• Barbiturates, propofol 

• Pyridoxine 

– Empiric dose, 5 gms (70 mg/kg) 

Excitation 

Inhibition 

Excitation 

Inhibition 


33 

The clinical management of seizures attempts to balance the loss of inhibitory tone by 

supplying a sedative that enhances inhibitory tone. Examples of sedatives that are 

given to control excitation and seizures include benzodiazepines, barbiturates and 

propofol. 

In selected circumstances, pyridoxine is also used, although it is not a sedative. It is a 

critical co-vitamin whose administration along with a benzodiazepine may be required in 

poisoning by monomethylhydrazine (rocket fuel) or INH (an anti-tuberculosis 

medication). 

Excitatory toxins cause convulsions and seizures which if prolonged can be rapidly fatal. 

The best way to treat this is to give inhibitory drugs or agents to stop the convulsions 

and seizures. Overly excited states are generally much more dangerous than overly 

inhibited states. In addition to the seizures and convulsions many excitatory agents 

cause changes in heart rate and blood pressure and other bodily functions that are often 

difficult to manage. In some cases the best treatment for an overly excited state is to 

use inhibitory agents to place the patient in a comatose and overly inhibited state which 

is easier to manage and can be maintained until the excitatory toxin effect has worn off. 

Benzodiazepines, barbiturates, and propofol are all examples of available 

pharmaceutical agents that can be used to produce inhibition and at high doses can be 

used to place the patient in a comatose state. Pyridoxine refers to vitamin B-6 which as 

described in the previous slide may be needed to treat convulsions and seizures from 

hydrazines or other compounds that interfere with normal vitamin B-6 usage in the brain. 

Although we give sedative agents to patients presenting with excitation, we never give 

excitation agents to patients with coma because the complications of causing undue 

excitation in these previously comatose patients outweighs the benefits of suddenly 

waking them up. Naloxone which is not a stimulant awakens opioid intoxicated patients 

NOT by stimulating them but by actually BLOCKING the opioid receptors and preventing 

continuing opioid effects. 





Slide 34 



www.squidy.150m.com 

“Playing with Our Mind ” 


34 

Let’s turn to the last concept – alteration of thought, often manifested as hallucinations. 

These screen shots are from Nightmare at 20,000 feet, a classic episode from the 1960s 

television series Twilight Zone. Bob Wilson (played by William Shatner), the character 

on this slide, is a salesman on a plane for the first time since his nervous breakdown six 

months ago. He spots a gremlin on the wing of the plane. Every time someone else 

looks out the window the gremlin moves out of view, so nobody believes Bob. Although 

at the end he is whisked away in a straitjacket, this was not drug-induced modulation of 

thought. However, if you have seen the show, it sends a chill up and down your spine 

knowing what he went through - both the difficulty in convincing others of what he had 

seen and dealing with his own fear. 





Slide 35 



Hallucinogens 

• Alter modulation of thought processes 

– Serotonergic 

– Sympathomimetic 

– Anticholinergic 

– Anesthetic (PCP and ketamine) 


35 

Although the actual mechanisms by which hallucinogens act on our brain vary, the 

clinical syndrome produced is qualitatively similar. We lose the ability to interpret and 

interact with our environment. There are a number of different classes of drugs which 

alter the modulation of the thought process. This slide lists 4 classes of drugs or 

chemicals that alter thought processes: serotonergic, sympathomimetic, anticholinergic 

and anesthetic. We will discuss examples of two of these (serotinergic and 

anticholinergic) in greater depth. 

Four of the classes of drugs or chemicals that alter modulation of thought processes are 

the following: 

1. Seroternergic – These drugs/chemicals after the transmission of the neurotransmitter 

serotonin. An example of an hallucinogenic agent which affects serotonin 

neurotransmission is LSD. 

2.Sympathomimetic – These drugs/chemicals stimulate the sympathetic nervous 

system. Norepinephrine (also known as adrenaline) is one of the neurotransmitters 

which serves as a modulator in the sympathetic nervous system. The street drug – 

methamphetamine – is an example of a sympathomimetic compound. Use of this drug 

can cause hallucinations. 

3.Anticholinergic – Drugs or chemicals that are anticholinergic block the neurotransmitter 

known as acetylcholine. Acetycholine is involved in a wide variety of bodily functions 

including muscle activity, heart (cardiac) activity and central nervous system (brain) 

activity. Anticholinergic drugs block the receptors which acetylcholine stimulate. By 

blocking these receptors anticholinergic drugs prevent normal function of the brain (and 

other target organs such as the heart and muscles). Hallucinations may result. An 

example of an anticholenergic drug is atropine. A plant with anticholinergic chemicals is 

jimson weed. 

4.Anesthetics – Some anesthetics – drugs used in anesthesia – also cause 

hallucinations. Ketamine is an anesthetic drug which at high doses frequently causes 





hallucinations. PCP (phencyclidine) is similar in structure to ketamine and causes 

hallucinations as well. 





Slide 36 



Serotonergic Hallucinogens 

• LSD 

• Tryptamines (DMT, 5 -MeO- 

DMT, psilocybin) 

• Ololiuqui (morning glory 

seeds) 


36 

Serotonin is a widely distributed neurotransmitter in the brain. Excess serotonin in 

certain regions of the brain leads to delirium and hallucinations. A number of intoxicants 

and drugs of abuse enhance the effects of serotonin including LSD, tryptamines, and 

some amphetamines. 

Many of these compounds have been abused for their hallucinogenic effects. LSD or 

“acid” is probably the most famous of these. 

Psilocybin is found in hallucinogenic mushrooms. DMT (dimethyl tryptamine) and 5- 

MEO-DMT (5-methoxy dimethyl tryptamine) are “designer drugs.” These drugs are 

chemical modifications of other drugs. Such modifications may enhance their 

hallucinogenic effects. 

Morning glory seeds (also known as ololiuqui) and other plant hallucinogens such as 

mushrooms and certain cacti are used recreationally for their effects. While they are 

unlikely to cause any permanent or serious harm to people exposed in a terrorist 

situation – they can incapacitate a large number of people and prevent them from 

responding rationally or appropriately to a given situation. 





Slide 37 



Serotonergic Hallucinogens 

• 1968 - The Yippies (Youth 

International Party) 

• Threatened to “space-out” or 

“turn on” the delegates to the 

Democratic National Convention 

in Chicago, and everyone else in 

Chicago as well, by dumping 

LSD into Lake Michigan. 


37 

In 1968 the Yippies threatened to “space out” delegates to the Democratic Convention 

by dumping LSD into Lake Michigan. Although highly potent, the amount of water in 

Lake Michigan would dilute the drug to the point of having no effect on people who drank 

it. Water contamination and dilutional effects will be discussed in greater detail in the 

Food/Water/Medication Module. 

LSD is potent at very small doses. However, given the tremendous volume of water in 

Lake Michigan, contaminating the Lake with enough LSD to produce a concentration of 

LSD in the water that would have caused any noticeable effect was very far-fetched. 

The dilutional effects of the water would have limited the LSD concentration to a 

negligible amount. 





Slide 38 



Anticholinergic Hallucinogens 

Atropine, Scopolamine and Hyoscyamine 


38 

Anticholinergic drugs can also cause hallucinations. At low doses they have beneficial 

therapeutic uses. At higher doses they may cause hallucinations. Cruise ship 

passengers often use scopolamine, an anticholinergic drug, in the form of a transdermal 

patch, to prevent sea sickness. Occasionally, passengers, who excessively absorb the 

scopolamine through their skin, begin to hallucinate. 

Teenagers may read on the Internet about a “free, natural, and safe” high that can be 

obtained if they brew a tea, or sometimes smoke seeds from the Thornapple or 

Jimsonweed plant (shown to the right). These plants have scopolamine and atropine 

(another anticholinergic agent) as their main ingredients and exposure to these 

chemicals may result in potent anticholinergic hallucinations –that may last for days. 

Anticholinergics chemicals are found in a wide range of drugs and plants. These include 

not only the plants mentioned above, but also a number of pharmaceutical agents 

including many antihistamines such as diphenhydramine. 





Slide 39 



• Mad as a hatter 

• Red as a beet 

• Dry as a bone 

• Hot as Hare 

• Blind as a bat 

• Full as a flask 

(Also decreased GI motility) 

Clinical Effects 


39 

The clinical effects produced by an anticholinergic drug or chemical can be remembered 

by recalling the first letter of this alliteration/poetic mnemonic: "blind as a bat, mad as a 

hatter, red as a beet, hot as a hell, dry as a bone, the bowel and bladder lose their tone, 

and the heart runs alone." 

The clinical effects from anticholinergic exposure include the following: 

1. Altered mental status – abnormal and often bizarre behavior where the patient may 

appear very agitated and often simply “delirious” or “mad.” These patients are often 

profoundly altered and may exhibit bizarre movements and appear to be picking at 

things. They are usually awake but often do not respond appropriately to questions and 

commands. Their speech is slurred and difficult to understand and their answers often 

have nothing to do with the questions asked of them. This type of delirium can be very 

disabling and may last for hours even to days depending on the particular anticholinergic 

compound and on the dose consumed. The “hatter” reference refers to workers who 

were exposed to mercury during the production of felt hats. While mercury is not an 

anticholinergic chemical, exposure to mercury could also result in an altered mental 

status. 

2. Red – patients appear quite flushed in appearance, almost as red as a beet 

3. Dry – patients suffering from anticholinergic effects often have very dry skin and do 

not perspire or sweat despite their agitation 

4. Hot – because of the agitation and the inability to sweat, patients often have elevated 

body temperature and fever 

5. Another anticholinergic effect is the presence of dilated pupils. The pupil size is often 

much larger than normal with each pupil measuring as much as 7 or 8 mm in diameter 

(normal pupil diameter is 3-4 mm). The dilation of the pupils is referred to as mydriasis. 

Patients with large pupils have difficulty focusing and because of their inability to focus – 

they may appear “blind” 





6. Anticholinergics also cause severe constipation and an inability to urinate. Hence 

these patients may appear very “full” and have a large distended bladder and their colon 

may be full of stool. 





Slide 40 



Modern History 

• 1676: a group of men led by Captain John Smith were sent 

to Jamestown, Virginia to quell the Bacon rebellion. 

• Gathered the plant now 

known as “Jamestown 

weed” (or Jimsonweed), 

Datura stramonium , for a 

salad. 


40 

An example of a mass poisoning with an anticholinergic compound occurred in 

Jamestown Virginia in 1676 during a colonial uprising known as Bacon’s rebellion. 

Of great toxicological interest, the British soldiers who were sent by the Colonial 

government to put down the rebellion ate a salad which mistakenly included 

Jimsonweed as one of its ingredients. The jimsonweed plant’s leaves (depicted an this 

slide) look like a more typical salad leaf (arugula), with scalloped edges and dark green 

color, and this is probably how the error occurred. 

Jimson weed contains the anticholinergic chemicals atropine and scopolamine. The 

picture on the slide also displays the characteristic tubular flower (not present in 

arugula). 





Slide 41 



Bacon Rebellion 

1676, Bacon Rebellion: 

The soldiers presented a “very pleasant comedy, for they turned 

natural fools upon it for several days: one would blow a feather in the 

air; another would dart straws at it with much fury; and another , stark 

naked, was sitting up in a corner like a monkey, grinning and ma king 

mows at them. …. A thousand such simple tricks they played, and 

after 11 days returned themselves again, not remembering anythin g 

that had passed. ” 

Robert Beverly, The History and Present State of Virginia (1705) 


41 

This is a description excerpted from a book written in 1705 about the Bacon rebellion. 

Of note, the anticholinergic hallucinations lasted 11 days. This is likely dose-related as 

the soldiers may have continued to eat the plant, and related to the long-lasting effects 

on the brain from repetitive administration. 





Slide 42 



July 1995 

Bosniaks fleeing Srebrenica during the war in Bosnia and Hercegovina . 

“Survivors gave consistent descriptions of mortar shells that pro duced a 

‘strange smoke ’ of various colors which did not rise but spread out 

slowly. Following these attacks, some of the marchers - the numbers 

are unclear - began to hallucinate and behave in an irrational manner, 

Human Rights Watch 

with some even killing their friends or themselves. . . . ” 

BZ: 3-Quinuclidinyl benzilate (QNB) 

Hay A. Surviving the impossible: the long march from Srebrenica. An in vestigation of 

the possible use of chemical warfare agents. Med Confl Surviv 1998;14:120 -55. 


42 

BZ is a chemical warfare agent with anticholinergic features, which has been 

weaponized by the military for possible battlefield use. Its use was implicated in the 

activities described above during the Bosnian exodus from Srebrenica in 1995. People 

exposed to BZ would be expected to develop an alteration in their mental status and 

exhibit hallucinations and act “mad.” 

BZ’s official chemical name is 3-Quinuclidinyl benzilate. Generally referred to as BZ, this 

chemical is also an anticholinergic agent. Exposure to BZ would result in anticholinergic 

effects such as those described in the previous slides. 

While BZ would not serve as a lethal weapon, the delirium that would result would 

render the adversary confused and disoriented and quite ineffectual to fight back. 





Slide 43 



Anticholinergic Hallucinogens 

• Qualitatively similar 

Atropine 

Scopolamine 

BZ 

Dose (70 kg) 

8-14 mg 

2 mg 

0.5 mg 

Duration 

4-8 h 

2-4 h 

48-72 h 


43 

Although these agents act generally the same, their potency (dose to have an effect) 

and the duration of effect is quite different. 

As can be seen on this slide, BZ is more potent than atropine and scopolamine because 

a lower dose is required to cause a comparable effect to those obtained with higher 

doses of the other anticholinergic agents. This slide also demonstrates that some 

anticholinergics have a much longer duration of action than others. The effects from BZ 

would be expected to last upwards of 2-3 days while the effects of atropine and 

scopolamine are much shorter acting lasting just a few hours. 





Slide 44 

Chemical Agents of Opportunity for 

Terrorism: TICs & 

TIMs 

Treatment 

strategy 

Excitatio 

n 

Inhibitio 

n 

Module 

Two 

- The Clinical Neurotoxicology of Chemical 

Terrorism 

4 

4 

Although the hallucinogenic agents disrupt our thought processes, our treatments 

usually focus on enhancing the inhibitory activity of the brain. 

In other words, we focus on sedation to counter delirium. As depicted on the slide, this 

treatment alters the individual’s balance of inputs - however, it is easier to provide care 

for and protect a sedated person than a delirious person. 

In the case of anticholinergic delirium, a specific antidote is available. The use of the 

cholinergic drug, physostigmine, can reverse all of the anticholinergic effects. This drug 

is a useful diagnostic – and therapeutic – tool. However, its duration of action is shor 

The see-saw depicts the effects of treating a hallucinating or delirious patient with a 

sedative, thus enhancing the inhibition of brain function. Note that this will result in a 

sedated patient, with all the potential downside of CNS and respiratory depression. 

However, it removes the potentially injurious effects seen in patients with altered thought 

processes due to unexpected and unpleasant hallucinations. 





Slide 45 



Concluding Thoughts 

• The CNS is a unique target organ for terrorism 

• Limited number of acute clinical consequences 

• Management is generally symptomatic although 

“antidotes” may be available for certain agents. 


45 

In conclusion, the central nervous system is a unique target for terrorism and there are 

many historical examples of its use to create social panic and fear. The use of 

neurotoxins as agents of terrorism however, will result in a limited number of acute 

clinical syndromes. Management of these syndromes is predominately symptomatic 

although antidotes may be available for certain agents. 

Global brain function can be altered in a limited number of ways (inhibition leading to 

sedation and coma; excitation leading to agitation and seizures; and altered thought 

processes leading to hallucinations and delirium). Recognizing these major toxidromes 

will allow better assessment of the chemical class(es) involved and allow appropriate 

treatment to be initiated. 





Slide 46 


Questions 


46 





Module Two Summary 

The Central Nervous System is a unique target organ for chemical terrorism. Despite its 

complexity, the brain really only displays its dysfunction in a limited number of ways. This 

includes CNS depression (sedation), CNS excitation (seizure) and possibly altered thoughts, as 

with hallucinations. Therefore, the use of certain chemicals as agents of terrorism will result in a 

limited number of acute clinical consequences. Management is generally symptomatic although 

“antidotes” may be available for certain agents. 

The normal state of the brain is maintained by balancing both excitation and inhibition, each 

mediated by a unique set of chemicals called neurotransmitters. We alter our neurotransmitters 

under normal conditions to suit our needs. For example, in order to sleep we increase inhibition 

and reduce excitations. Other neurotransmitters play a role in our functional abilities, or our 

ability to process information smoothly. For example, Serotonin and Acetylcholine serve as 

modulators of our thought processes. Chemical (drugs) typically cause sedation or coma by 

enhancing our inhibitory tone, not by reducing excitation. Chemicals (drugs) typically cause 

seizures by enhancing excitation or reducing inhibition. The alteration of the flow of information 

in our brain results in hallucinations. Sensory input is unfiltered resulting in sensory overload, 

causing hallucinations. 

Sedatives have the potential to be used by terrorists. The Moscow theater hostage crisis was 

the seizure of a crowded Moscow theatre on October 23, 2002 by about 40 armed Chechen 

militants. They took 850 hostages and demanded the withdrawal of Russian forces from 

Chechnya and an end to the Second Chechen War. After a two-and-a-half day siege, Russian 

special forces pumped weaponized Fentanyl (maybe carfentanil)- into the building's ventilation 

system and raided it. Officially, 39 of the terrorists were killed by Russian forces, along with at 

least 129 of the hostages. Some estimates have put the civilian death toll at more than 200 

people. 

Most central nervous system depressants are associated with some degree of respiratory 

depression. Some like the opioids are associated with profound respiratory depression, 

explaining the high fatality rate in the Moscow theater. The opioid toxidrome (toxicological 

syndrome) is relatively easy to recognize, particularly for medical personnel, since it is 

commonly noted in heroin users. Treatment involves administration of an antidote called 

naloxone (Narcan). Ventilatory support may be necessary and for extended periods of time. 

The use of toxic convulsants creates another clinical syndrome that may appear convulsions or 

seizure. The term seizure refers to the underlying brain activity whereas convulsion is what you 

see when you look at the patient; the movement. Some convulsant toxins are not seizure 

inducing, such as strychnine. 

Tetramine (rat poisoning) has been reportedly used several times in epidemic poisoning in 

China. Other convulsant poisons that are relatively easy to access include organophosphorus 

and carbamate insecticides, along with nicotine, hydrazines, camphor, and organochlorines and 

strychnine.. Their use in an act of terrorism is a distinct possibility. The clinical management of 

seizures attempts to balance the loss of inhibitory tone by supplying a sedative that enhances 

inhibitory tone. 

Hallucinogens. Although the actual mechanisms by which hallucinogens act on our brain vary, 

the clinical syndrome produced is qualitatively similar. We lose the ability to interpret and 

interact with our environment. Hallucinogens may be used by terrorists as incapacitating agents. 





The anticholinergic hallucinogens have a long history of use, and drugs such as scopolamine 

are in current use as transdermal patches. A common occurrence on cruise ships is an elderly 

passenger who is using a transdermal scopolamine patch who begins hallucinating due to 

excessive absorption through their thin skin. The treatment for hallucinations is generally 

supportive with the additional use of sedatives (enhancing inhibition) to allow the drug to be 

eliminated. 

In conclusion, The CNS is a unique target organ for terrorism yet there are a limited number of 

acute clinical consequences that may result from the deliberate exposure to toxins. 

Management is generally symptomatic although “antidotes” may be available for certain agents. 





Module Three 

Toxic Industrial Gases as Terrorist Threats - Administration 

Page 

Chemical compounds are produced in massive quantities as part of America's industrial 

complex. Many of these compounds are amenable to use as large scale terrorist weapons. 

These chemicals are produced, transported, and stored in communities across our nation and 

are easily accessible by all. These chemicals pose a significant health risk to individuals and 

populations should they be released either intentionally or accidentally. Exposure to toxic gases 

will create serious health implication for victims. Many of these irritive gases, such as chlorine, 

phosgene, and ammonia, exert their effects by the production of corrosive agents, such as 

hydrochloric acid and ammonium hydroxide. Other agents, such as hydrofluoric acid, also 

produce systemic effects. Individual characteristics of each gas will determine its toxicity and 

health effects. Quick response and appropriate clinical management will be critical to reducing 

morbidity and mortality. Prevention includes methods to decrease the likelihood of exposure and 

mitigation efforts will be important. Current legislation under the community right to know act 

mandates disclosure of the presence of toxic chemicals within communities. 

Duration 

45 minutes 


This module will address a number of chemicals, such as phosgene, chlorine, and anhydrous 

ammonia, which might be disseminated as inhalational threats. Historical examples of the 

release of these gases and their impact on the community will be reviewed. Their 

pathophysiology, treatment, and potential sources in the community and in the transportation 

system will be discussed. 


• Understand the threat posed by toxic industrial gases and the 

recognition, assessment and management of exposed patients. 


Resources 

• Review the history of industrial gas exposures and regulatory 

response 

• Identify major compounds of interest 

• Understand the varying clinical picture created by the gases, based 

on their physical properties and toxicity 

• Address methods to decrease likelihood of exposure and illness 













1. AEGL List of Chemicals: 

http://earth1.epa.gov/oppt/aegl/pubs/chemlist.htm 

2. ATSDR ToxFAQs (choose by chemical): 

http://www.atsdr.cdc.gov/toxfaq.html 

3. ATSDR Medical Management Guidelines: 

http://www.atsdr.cdc.gov/MHMI/mmg.html#bookmark03 

4. Bardana EJ Jr. Reactive airways dysfunction syndrome (RADS): 

guidelines for diagnosis and treatment and insight into likely 

prognosis. Ann Allergy, Asthma, Immunol 1999; 83(6 Pt 2):583-586. 

5. Belke JC. Chemical accident risks in U.S. industry -A preliminary 

analysis of accident risk data from U.S. hazardous chemical facilities. 

Last accessed Dec 2008 from: 

http://www.epa.gov/ceppo/pubs/stockholmpaper.pdf 

6. Bosse GM. Nebulized sodium bicarbonate in the treatment of chlorine 

gas inhalation. J Tox Clin Tox 1994;32(3):233-241. 

7. BP Facilities Lead Nation in Chemical and Refinery Accidents Since 

1990, Despite Industry-Touted Safety Measures” (Report by Texas 

Public Interest Research Group on HF Release). Last accessed Dec 

2008 from: http://www.commondreams.org/news2005/0324-09.htm 

8. CDC. Public Health Consequences from Hazardous Substances 

Acutely Released During Rail Transit ---South Carolina, 2005; 

Selected States, 1999-2004. MMWR 54(3):64-67. Last accessed Dec 

2008 from: 

http://iier.isciii.es/mmwr/preview/mmwrhtml/mm5403a2.htm 

9. Chemical Safety and Hazard Investigation Board (listing of chemical 

company events and investigations): http://www.chemsafety.gov/ 

10. Chin S-M, Hwang H-L, Peterson BE. “A Tool for Railroad Hazmat 

Routing Under Shipment Bans In Major Cities” [PowerPoint 

presentation from Oak Ridge Laboratory at Transportation Research 

Board 85th Annual Meeting, 2006]. Last accessed Dec 2008 from: 

http://projects.battelle.org/trbhazmat/Presentations/TRB2006-LH.ppt 

11. Dhara VR, Dhara R. The Union Carbide disaster in Bhopal: a review 

of health effects. Arch Environ Health 2002;57:391-404. 

12. EPA’s Acute Exposure Guideline Levels (AEGL) Definitions: 

http://earth1.epa.gov/oppt/aegl/pubs/define.htm 

13. EPA’s High Production Volume Information System (characterizing 

chemicals produced or imported at > 1 million pounds): 

http://www.epa.gov/hpvis/ 





14. EU Health & Safety Executive report from Control of Major Accidental 

Hazards- COMAH. Last accessed Dec 2008 from: 

http://www.hse.gov.uk/comah/sragtech/caseuncarbide84.htm 

15. Klasner A, Scalzo A, Blume C, Johnson P, Thompson M. Marked 

hypocalcemia and ventricular fibrillation in two pediatric patients 

exposed to a fluoride-containing wheel cleaner. Ann Emerg Med 

1996;28(6):713-718. 

16. Lapierre D and Moro J. Five Past Midnight in Bhopal: The Epic Story 

of the World’s Deadliest Industrial Disaster. Hatchett Book Group, 

Grand Central Publishing, New York; 2002. 

17. Lee DC, Wiley JF 2nd, Synder JW 2nd.Treatment of inhalational 

exposure to hydrofluoric acid with nebulized calcium gluconate. J 

Occup Med 1993;35:470. 

18. Military Textbook of Medicine: Medical Aspects of Chemical and 

Biological Warfare. Last accessed Dec 2008 from: 

http://www.bordeninstitute.army.mil/published_volumes/chemBio/Ch9. 

pdf 

19. Muller, R. A Significant Toxic Event: The Union Carbide Pesticide 

Plant Disaster in Bhopal, India, 1984. Last accessed Dec 2008 from: 

http://www.tropmed.org/rreh/vol1_10.htm 

20. National Library of Medicine ChemIdLite Site (choose by chemical; 

access to databases): 

http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp 

21. National Research Council. Emergency and Continuous Exposure 

Limits for Selected Airborne Contaminants, V2;National Academy 

Press, Washington D.C.; 2000. Last accessed Dec 2008 from: 

http://books.nap.edu/openbook.phprecord_id=690&page=69 

22. National Transportation Safety Board Graniteville SC crash accident 

report. Last accessed Dec 2008 from: 

http://www.ntsb.gov/publictn/2005/RAR0504.pdf 

23. Noltkamper D, Burgher SW, Toxicity, Phosgene. eMedicine from 

WebMD. Last accessed Dec 2008 from: 

http://www.emedicine.com/emerg/topic849.htm 

24. Sriramachari S, Chandra H. Pathology and toxicology of methyl 

isocyanate and MIC derivatives in Bhopal disaster. Last accessed 

Dec 2008 from: 

www.anchem.su.se/isocyanate2000/abstracts/abs_chandra.html 

25. Wibbenmeyer LA, Morgan LJ, Robinson BK, et al. Chemical burn 

injuries: exposing the dangers of anhydrous ammonia. Journal of Burn 

Care & Rehabilitation 1999;20 (vol 3):226-232. 

26. Woodward JL, Woodward HZ. “Analysis of hydrogen fluoride release 

at Texas city.” Process Safety Progress 2004;17(3):213-218. 

27. World Health Organization. Health and Safety Guide No. 106: 

Phosgene. International Programme on Chemical Safety (IPCS); 






Geneva, 1998. Last accessed Dec 2008 from: 

http://www.inchem.org/documents/hsg/hsg/hsg106.htm 


















Module Three 

Icon Map 






instruction 





Slide 1 


Module Three 

Toxic Industrial Gases as Terrorist Threats 


1 

This lecture will focus on high production volume industrial gases that are present 

throughout the country, the threat they pose as terroristic agents, and the measures 

taken to reduce that threat. 





Slide 2 



Learning Objectives 

• Review history of industrial gas exposures and 

regulatory response 

• Identify major compounds of interest 

• Understand the varying clinical picture created by 

the gases, based on their physical properties and 

toxicity 

• Address methods to decrease likelihood of exposure 

and illness 

Module One – Toxic Industrial Gases as Terrorist Threats 

2 

Beyond just identification of some of the major compounds in this group, this 

presentation will provide the participant with an understanding of the characteristic 

toxidromes associated with these gases, and familiarity with the national legislative and 

regulatory framework and local implementation that encourages threat reduction. 

The learning objectives for this module are as follows: 

Review history of industrial gas exposures and regulatory response 

Identify major compounds of interest 

Understand the varying clinical picture created by the gases, based on their physical 

properties and toxicity. We will discuss the physical properties in detail with each gas. 

Of note, the type of clinical injury seen is dependant not only on dose and inherent 

toxicity, but also water solubility. 

Address methods to decrease likelihood of exposure and illness 





Slide 3 



Key Learning Points 

• Legislation to regulate TICs/TIMs was generated by concerns 

regarding toxic gases 

• Releases of large volumes of compressed gas is the most 

likely TIC/TIM scenario 

• Toxicity of a gas is determined by 

– Dose 

– Inherent toxicity 

– Volatility 

– Water solubility 

– Warning properties 

– pH 


3 

Recognize that much of the chemical legislation in this country and elsewhere grew out 

of concern following large-scale exposures. We will present several major chemical 

releases in this module. 

By far, releases of these agents form the most likely TIC/TIM scenario. These are the 

physical characteristics of an irritant gas that predict its specific toxicity – in particular, 

water solubility. 

Toxicity of a gas is determined: 

Dose 

Inherent toxicity 

Volatility 

Water solubility 

Warning properties 

pH 





Slide 4 



The Bhopal Disaster (1984) 

• Methyl isocyanate (MIC) 

release 

Union Carbide plant in 

Bhopal, India (December 3, 

1984) 

http://www.lenntech.com/environmental 

-disasters.htm 


4 

Releases of toxic industrial gases form the most likely TIC/TIM scenario. 

Much of the chemical legislation in this country and elsewhere grew out of concern 

following large-scale exposures. 

The release of more than 40 tons of methyl isocyanate (MIC) from the Union Carbide 

plant in Bhopal, India in December 1984 is the best example of a large-scale industrial 

release of a gas. Although this is generally considered to be an industrial accident, it 

highlights many key features of a terrorist event, including the scope of injury – both 

acute and chronic, the failure of control measures, and the inadequacy of medical 

response. There were considerably more casualties and more deaths from this 

industrial event than any terrorist event to date. 

This slide depicts some of the features of the methyl isocyanate release and failures of 

intended control measures at the Union Carbide plant in Bhopal, India. This plant was in 

the process of being shut down and staffing and maintenance were not at their usual 

levels. 





Slide 5 



Bhopal Disaster 

• Water entered tank containing 57,000 L MIC 

– sabotage 

• Exothermic reaction 

• Release of >40 tons MIC over 2 hrs 

• Multiple safety system failures 

– unreliable pressure gauges 

– nonfunctional refrigeration unit 

– inoperable gas scrubber 

– alarm failure 

– Inadequate spray “knock -down” 


5 

During this event, which occurred in the middle of the night, water entered a tank that 

was supposed to be empty, but actually contained about 57,000 liters of MIC, resulted in 

an exothermic reaction with the massive release of more than forty tons of MIC over a 

couple of hours, which then drifted downwind over the slums of Bhopal. The release 

itself involved multiple system failures in terms of plant based operations that were 

supposed to prevent or mitigate against this type of event. Pressure gauges were not 

functioning, the refrigeration unit was not functioning, there was an inoperable scrubber 

that should have reduced or knocked down some of the ascending plume, and alarms 

failed, resulting in a large release over this area. 





Slide 6 




• Gas plume drifted over shanty - 

town exposing 250,000 people 

• Temperature inversion reduced 

plume dilution 

• Extent of risk: 

– Modeled mean MIC ambient 

concentration: 27 ppm (range 

0.12 -85.6 ppm) 

– Median MIC concentration: 1.8 

ppm 

– 30 minute Acute Emergency 

Guideline Level -3 (AEGL3) 0.40 

ppm 

http:// www.bhopal.org/whathappened.html 


6 

Approximately 250,000 people were exposed to the MIC gas fume. A temperature 

inversion in the local area reduced the extent of a plume dilution effect that would have 

occurred under normal weather conditions. After the fact, modeling suggested a median 

air concentration of MIC of 1.8 ppm. This exceeded the AEGL-3 of 0.40 ppm which was 

the predicted airborne concentration above which people are likely to experience life 

threatening health effects or death. 

Temperature inversions occur when the temperature of the atmosphere increases with 

height. During a temperature inversion, warm air traps cool air below, acting like a lid. 

Pollutants below the inversion are trapped, allowing them to build up. In the Bhopal 

case the temperature inversion limited the usual dilutional effect of the chemical plume 

increasing the airborne concentration of the MIC. 

AEGLs are “acute exposure guideline levels” which have been developed for a number 

of chemicals. The modeled concentrations after this release were quite a bit above the 

threshold for devastating health effects, consistent with the actual events. 

The map on the slide depicts the modeled distribution of the methyl isocyanate plume 

following this release. The darker shading indicates higher gas concentration. The extent 

of heavy concentration represents the lack of dilutional effect from the temperature 

inversion and low wind speed. Note the extension in all directions with more prominence 

towards the south, also representing the effects of a low wind speed. 





Slide 7 




• 2500 fatalities within 1 week 

• Long term mortality 

estimated ≥ 6000 

• Chronic disability for > 

100,000 () 

– chronic pulmonary complaints 

– ocular inflammation 

Dhara et al, Arch Environ Health 2002; 57:391 -404 


7 

The numbers of deaths and injuries from this disaster had never previously been seen 

from an industrial accident. Within the first week more than 2000 residents of Bhopal 

died from the acute toxic effects of this chemical release. Additional thousands died in 

the ensuing weeks and months. Long term pulmonary and eye injuries were thought to 

have affected at least 100,000 people. 





Slide 8 



Methyl Isocyanate (MIC): 

H3C–N=C=O 

• Used as a chemical intermediary for many products, 

including carbamate insecticides, polyurethane foam 

and a variety of plastics 

• Usually produced by reacting methylamine and 

phosgene with release of hydrochloric acid 

• A high production volume chemical, as are its 

reagents 

• Combustion products from MIC may include cyanide 

and carbon monoxide 


8 

Prior to the Bhopal disaster, relatively little was known about methyl isocyanate. The 

Bhopal plant was producing a carbamate pesticide called carbaryl (Sevin). Methyl 

isocyanate was a chemical intermediate that was produced in the production of this 

pesticide. Although MIC has the term “cyanate” in its name, a release of MIC does not 

produce cyanide. Only when MIC undergoes combustion or pyrolysis (when it is burned) 

does cyanide (and carbon monoxide) get produced. The exothermic reaction in the 

Bhopal event likely produced some of these other toxic gases, although a fire did not 

occur with the MIC release at Bhopal. 





Slide 9 



Methyl Isocyanate : 

Physical Properties 

• Colorless, flammable liquid at room temperature, but 

easily vaporizes 

– Vapor pressure 348 mm Hg 

– Boiling point 39.5 °C 

• Has a pungent odor; inadequate warning 

• Water soluble, but with exothermic reaction 

• Vapor density: 1.4 


9 

This slides illustrates some of the chemical properties of methyl isocyanate. The high 

vapor pressure and low boiling point mean this is a highly volatile liquid. It has a pungent 

odor but detection of this odor does not adequately warn someone who is exposed to 

MIC to immediately leave the source of exposure. The vapor density means it is 

somewhat heavier than air (which has a vapor density of 1). 

Vapor densities are compared to that of air. 

MIC odor threshold is in the range of 2ppm – this does not provide an adequate warning 

of potentially harmful exposure (the Occupational Health and Safety Administration has 

set the Permissible Exposure Limit – for a 40 hour work week for a working lifetime: 

OSHA PEL 0.02ppm) 





Slide 10 



Methyl Isocyanate : Clinical Effects 

• Dermal/ocular 

– Irritation and ulceration 

• Respiratory 

– Mucosal irritation of upper and lower respiratory tract 

– Life-threatening pulmonary edema 

– Residual chronic lung disease 

• Reactive Airways Dysfunction Syndrome (RADS) 


10 

The clinical effects of methyl isocyanate predominantly involve 3 organ systems: skin 

(dermal), eyes (ocular) and lungs (respiratory). In each of these cases, methyl 

isocyanate acts as a potent irritant. Although the eye and skin manifestations may cause 

significant discomfort and distress and chronic disability, the life threatening effects 

occur from the pulmonary effects. A chemical pneumonia and pulmonary edema may 

result causing decreased oxygenation and air hunger. Overwhelming pulmonary 

compromise may result in death. 

RADS is a chronic pulmonary problem that may develop after an acute exposure to MIC. 





Slide 11 



Reactive Airways Dysfunction 

Syndrome (RADS) 

• Non-immunologic asthmatic condition following large 

exposure to certain irritants 

• Syndrome diagnosis requiring: 

– No prior chronic respiratory illness (including asthma) 

– Documented exposure to chemical irritant in significant amount 

– Onset of symptoms (cough, dyspnea , wheezing) within 24 hours and 

persistence for >3 months 

– Demonstrated airway obstruction and bronchial hyper -responsiveness 

by pulmonary function testing 

– Lack of other competing pulmonary diagnosis 


11 

Reactive airways dysfunction syndrome (RADS) is a chronic condition that sometimes 

develops after an exposure to a “sensitizing” irritant such as methyl isocyanate. The 

symptoms resemble asthma. Prior to the exposure to the irritant, the patient may not 

have had any preexisting pulmonary condition such as asthma. The symptoms of RADS 

– cough, shortness of breath and/or wheezing – typically develop within 24 hours of the 

exposure. These symptoms may last for months (or even longer). 





Slide 12 



SARA 

• Emergency Planning and Community Right -to-Know 

Act of 1986 (SARA Title III) 

• State Emergency Response Commissions 

• Local Emergency Planning Committees 

• Chemical facilities submit annual inventory reports 

about hazardous chemicals 

http://www.access.gpo.gov/nara/cfr/waisidx_04/40cfr372_04.html 


12 

In response to the Bhopal tragedy and increasing community concern regarding 

hazardous materials, the US Congress passed several laws intended to minimize the 

likelihood and consequences of catastrophic chemical events 

The SARA Title III is the first of several laws that were passed by Congress. This law is 

known as the “Emergency Planning and Community Right-to-Know Act (EPCRA).” It 

requires states to create State Emergency Response Commissions (SERCs) and 

communities to form Local Emergency Planning Committees (LEPCs) for the goal of 

preparing emergency response plans for chemical accidents. It also requires chemical 

facilities to provide annual inventory reports and information about hazardous chemicals 

for use in emergency planning. The focus of these laws is on ACCIDENTAL releases. 

SARA Title III: The Emergency Planning and Community Right-to-Know Act (EPCRA) 

establishes requirements for Federal, State and local governments, Indian Tribes, and 

industry regarding emergency planning and “Community Right-to-Know” reporting on 

hazardous and toxic chemicals. The Community Right-to-Know provisions help increase 

the public’s knowledge and access to information on chemicals at individual facilities, 

their uses, and releases into the environment. States and communities, working with 

facilities, can use the information to improve chemical safety and protect public health 

and the environment. 





Slide 13 



Clean Air Act Amendments of 1990: Risk 

Management Plans (RMP) 

• Businesses required to prepare RMP if greater than threshold 

amount present of any of 77 toxic or 63 flammable 

substances 

• EPA reviews for completeness, NOT accuracy 

• RMP must include 

– Identity of type and amounts of hazardous materials 

– Accident history during past 5 years 

– Hazards associated with chemical processes 

– Process controls, mitigation systems, detection systems 

• Off-site consequence analysis (OCA) 

• No information on site security is included 

http://www.epa.gov/fedrgstr/EPA -AIR/2004/April/Day -09/a7777.htm 


13 

While the SARA Title III laws mandated that industry provide information on the 

inventory of hazardous chemicals used at their facilities, these laws contained no 

provisions for the prevention of chemical accidents. 

The 1990 Clean Air Act Amendments addressed this “prevention” issue and contains 

two provisions for the prevention and minimization of chemical accidental releases. This 

is the basis of the EPA’s “Risk Management Plans” (RMP) for Chemical Accidental 

Release Prevention. This slide details the requirements of these Risk Management 

Plans. 

Off-site Consequence Analysis (OCA) is the process of determining the worst case 

scenario for an ACCIDENTAL release. This is defined as a release of the maximum 

amount of a chemical involved in a single process or storage vessel, using models that 

define calm environmental conditions, equal spread in all directions. No active release 

mitigation steps are included, although passive efforts such as building enclosures are 

included. 





Slide 14 



DHS Chemical Facility Antiterrorism 

Standard (Interim Final Rule 2007) 

• Risk-based focus on facility security and 

improvements 

• Security Vulnerability Assessments and Site 

Security Plans 

• Mandates audits and inspections 

• Penalties for non -compliance 

• Confidential information – preventing “inappropriate 

public disclosure ” 

http://a257.g.akamaitech.net/7/257/2422/01jan20071800/edocket.ac cess.gpo.gov/2007/E7 -6363.htm 


14 

Under the 2007 Chemical Facility Anti-Terrorism Standards, Congress directed the 

Department of Homeland Security (DHS) to issue regulations "establishing risk-based 

performance standards for the security of chemical facilities." Many states have initiated 

Hazard Vulnerability Assessments of their chemical facilities. 

According to DHS, security risk is a function of the following: 

o the consequence of a successful attack on a facility (consequence), 

o the likelihood that an attack on a facility will be successful (vulnerability) 

o the intent and capability of an adversary in respect to attacking a facility (threat). 

There are also provisions within this act addressing audits, inspections, and penalties for 

non-compliance, as well as security of the data generated in complying with the act. 





Slide 15 

EPA has published the results from the first five years of data collection under the Risk 

Management Plans. 

There were 1,913 reported accidents, with a TOTAL of 2,038 injuries and 75 deaths 

during this five year period. This is an abbreviated list of the most commonly spilled 

chemicals. We will spend the remainder of this module focusing on the highlighted 

compounds, which constitute the vast majority of releases to date or – in the case of 

phosgene – have both historical and toxic significance. These agents are commonly 

present in the community, present a real threat, and typify gas inhalational injury. 





Slide 16 

Before we cover some of these other major industrial gases, it is important to increase 

our understanding of the determinants of inhalation exposure. There are several key 

factors that determine the toxicity associated with a gas exposure. These factors include 

the underlying health of the individual exposed, the exposure circumstances and the 

specific properties of the chemical agent. The DOSE of the inhalational exposure is 

determined by the concentration, respiratory rate, and duration of chemical exposure. 

Ultimately the dose, along with the chemical properties and the health of the individual 

exposed will determine the severity of injury. The DOSE is critically important as 

something that may be only irritating (sneeze, “tickle in the throat”, uncomfortable) at low 

concentration or short-term exposure may become injurious (tissue damage, edema, 

inflammation and scarring) at much higher doses. 





Slide 17 



Clinical Effects Based on 

Properties of Agent 

High 

Solubility 

Low 

Solubility 

Onset of 

Symptoms 

Warning 

Properties 

Airway 

Injury 

Rapid 

Good 

Upper with 

irritation 

Delayed 

Poor 

Lower with lung 

injury 


17 

The anatomic site of injury depends on the water solubility of the substance inhaled. 

High water solubility gases tend to have a rapid onset of symptoms and predominantly 

affect the upper airways. Low water solubility gases tend to have a delayed onset of 

symptoms and predominantly affect the lower airways. 

Simplistically, these gases can be separated into their usual effects based on water 

solubility. Individual exposure characteristics may modify this, but – when forming a 

case definition – these characteristics provide a reliable framework. Exposure to a very 

water soluble irritant substance will force someone to flee (if possible) before a sufficient 

dose (concentration x duration) reaches the lower airways because of the irritation 

caused by it being dissolved in tear film and saliva/mucous of the upper airways. Of 

course, these distinctions may not hold true in an overwhelming situation (massive 

exposure) or where escape is not possible. At high doses (prolonged exposure or very 

high concentrations or both), the distinction between irritation and injury will become 

blurred or lost. 





Slide 18 



• Irritancy 

Comparative Toxicity Of Likely 

Terrorist Industrial Gases 

• Danger/Lethality 

Ammonia > Phosgene 

Phosgene > Ammonia 


18 

Given the same dose – concentration and duration of exposure – ammonia (to be 

discussed next) which is water soluble –tends to be much more irritating then phosgene 

which is poorly water soluble. However, phosgene (to be discussed later in this talk) 

which is far less irritating in the acute exposure setting, is far more lethal given similar 

exposure concentrations. 

The fact that phosgene is far more lethal at equivalent concentration is borne out by the 

different 30 minute AEGL3 (major or life threatening impact) for these two compounds. 

For ammonia the 30 minute AEGL3 is 1600 ppm while for phosgene the equivalent 

value is 1.5 ppm. This data suggest that at equivalent airborne concentrations phosgene 

is 1000 times as potent as ammonia. 





Slide 19 



Railway Accident: Minot, ND 2002 

• Derailment of 31 cars 

• Immediate release of 

~150,000 gallons of 

anhydrous ammonia 

from 5 of 15 cars 

• One car airborne _ mile 

striking a house 

• Plume 300 feet high 

spreading 5 miles 

downwind 

http://www.ntsb.gov/publictn/2004/RAR0401.pdf 


19 

This next case study demonstrates the toxicity associated with an ammonia exposure. 

On January 18, 2002 at 1:37AM, a major train derailment (secondary to a rail break from 

fractured joint bars) occurred approximately 0.5 mile west of Minot, ND. A total of 31 

cars derailed, 15 of which contained anhydrous ammonia. Five of these 15 lost all of 

their contents, immediately releasing an estimated 146,700 gallons of anhydrous 

ammonia which created a visible plume spreading for 5 miles. Six other cars leaked 

contents (74,000 gallons) over the next 5 days. 





Slide 20 



Response and Outcomes 

• Shelter-in-place order 

• Difficulty with communication 

• Exposed population: 11,600 

– Minor symptoms: 322 

– Serious symptoms: 11 

– Fatal: 1 


20 

Initial calls to 911 resulted in local activity, but there was a problem getting messages to 

the community, as the designated emergency broadcast TV station did not have an 

overnight crew. Although the population at risk for exposure exceeded 10,000, only 3% 

of those who were at risk for exposure developed symptoms and less than 0.1% 

developed serious symptoms. There was one death. 

In addition, power outages from the crash and siren positioning affected message 

dissemination. The one death was a man who was driving away from the area of the 

crash, became overcome by the ammonia, and struck a house. He then got out of the 

vehicle and collapsed. Rescuers were unable to extract him and neighbors were unable 

to go outside to help because of the noxious gas. Yet they were relatively unaffected 

“sheltering in place.” 





Slide 21 



Anhydrous Ammonia (NH3) 

• Used mainly in manufacture of fertilizer as nitrogen source 

(>80%) 

• Other uses include plastics, fibers and resins, explosives, 

cleaning disinfectants, refrigeration 

• Third highest production volume chemical in U.S. 

– ~9 million metric tons 

• Transported as liquefied gas under pressure via pipeline, 

railcar, tanker truck, and refrigerated barge 


21 

Anhydrous ammonia is the third most produced chemical in the US. The term 

anhydrous emphasizes the absence of water in commercial strength ammonia. Most of 

the anhydrous ammonia produced worldwide is used for fertilizer. Its high nitrogen 

content makes it one of the best fertilizers available commercially. It is also used as an 

intermediary or component in a number of other industrial processes. Because of its 

widespread use in large quantities, it is also transported long distances by a variety of 

mechanisms. 

Anhydrous ammonia is applied either by injection of the anhydrous gas directly into the 

soil, or as an aqueous solution or various salts. It is used in the manufacturing of 

plastics, pesticides, explosives and pharmaceuticals. It is found as a refrigerant gas in 

commercial installations. 

In contradistinction to commercial strength ammonia, household ammonia used for 

disinfecting and cleaning in the house is actually ammonium hydroxide. Ammonium 

hydroxide is ammonia and water. The typical ammonia concentration is about 5-10% in 

this household product. 





Slide 22 



Ammonia: Physical Properties 

• Colorless gas with pungent odor 

• Low odor threshold; good warning properties 

• Highly water soluble 

• Boiling point – 33°C 

• Vapor density 0.6 (lighter than air) 

• Combustible in narrow range 

• Highly reactive gas 


22 

Anhydrous ammonia at standard atmospheric pressure and temperature is a colorless 

gas with an extremely pungent odor. It has high water solubility causing irritation on 

contact. This combined with its low odor threshold (5-50 ppm) result in good warning 

properties. (NIOSH TWA 25ppm). When anhydrous ammonia escapes from a 

pressurized system, it may appear as a white plume. It is combustible at a concentration 

of 15-25%; but pressured canisters can easily explode in heat and fires or with impact – 

as occurs in railroad crashes. Note that it is lighter than air, but the density of a recently 

released pressurized liquid is higher, so it may continue to “hug the ground” near site of 

release. 





Slide 23 



Clinical Effects 

• Damage from alkali burn and thermal reaction 

NH 3 + H 2 O NH 4 OH 

• Low concentration: irritant to nose, throat, upper respiratory 

tract 

• Higher concentrations or more prolonged contact 

– Skin burns: 30% of admitted chemical burns attributed to ammonia 

(variable by extent of clandestine drug labs) 

– Lower airway inflammation with pneumonitis and pulmonary edema 


23 

Ammonia is an irritant at low concentrations and a corrosive at higher concentrations. 

Given that ammonia is a water-soluble gas, typical symptoms seen at lower 

concentrations affect the upper airways including the nose, throat, and trachea. At higher 

concentrations, or with more prolonged contract, anhydrous ammonia acts as a 

corrosive and may cause burns to tissues exposed to concentrated amounts. 







Anhydrous Ammonia 

• Concentration and duration of exposure determines clinical 

effect 

– From minor irritation to blindness with extensive scar formation 

• Center picture shows fluorescein uptake indicating diffuse 

corneal injury 


24 

This slide demonstrated what happens when anhydrous ammonia comes in contact with 

the eye. The cornea which covers the eye is very sensitive to minor irritation. A 

corrosive exposure (higher concentration and/or more prolonged contact) may cause a 

chemical burn to the cornea and result in irreversible scarring. These photos illustrate 

what may occur after such a corneal injury. The intense fluorescein staining (a greenish 

dye under UV light) shown in the middle at the time of injury led in this case to 

irreversible scarring and blindness. 

The photo on the left demonstrates inflammation of the conjunctiva and cornea – the 

epithelial layer covering the eye (conjunctival “injection” or vascular congestion, and 

corneal clouding – appears as opaqueness – secondary to corneal edema). The middle 

photo shows what occurs when the green fluorescein dye is applied to the cornea and 

viewed with an ultraviolet light. With a normal cornea there should be no uptake with the 

fluorescein. The uptake of fluorescein in this middle photo suggests widespread injury to 

the cornea. 

The photo on the right shows the long term results of a chemical burn to the eye and 

subsequent scar formation. In the scarred eye, blood vessels grow into the tissue. The 

scarring results in a permanent opacity in what is suppose to be a translucent cornea. 

Such an opacity results in blindness. 





Slide 25 



Next Gas: 

Homemade WWI Warfare Agent 

• 29 yr old man with acute respiratory distress after 

cleaning toilet 

• RR 36/min, HR 128/min, BP 148/76 

• Lip and throat swelling 

• Diffuse wheezing 

• Required intubation 

and positive pressure 

ventilation 

• Hypoxia with CXR 


25 

The next toxic gas we will discuss has a long history of use as a chemical warfare agent. 

This young man developed symptoms while at home cleaning his bathroom. The rapid 

onset of mucous membrane irritation, rapid respirations, upper airway and lower airway 

injury suggests exposure to an intermediate water-soluble irritant. The low oxygenation 

and Chest X-ray abnormalities (shown on next slide) indicate the degree of lung injury. 

The patient presents with a number of abnormalities as a result of his exposure to 

chlorine. These include a rapid respiratory rate (RR). Normal respiratory rate is 16-20. 

This patient has a much faster respiratory rate suggesting some type of respiratory 

distress. In addition the HR (heart rate) is also increased to 128 (normal 60-100). This 

occurs from the stress – physiologic and psychologic (pain, hypoxia, sympathomimetic 

response) - that develops after a significant toxic gas inhalation. 

Given the irritating effects of the chlorine, tissues that are in contact with the chlorine 

such as the lips and throat will become edematous (swell up) as a part of the 

inflammatory response. In a more significant exposure the lungs can be affected and 

the patient can develop wheezing which may resemble asthma. 

Patients with significant lung involvement may develop hypoxia. Hypoxia refers to a 

condition of inadequate oxygenation – in this case due to lung injury and the inability to 

transfer oxygen from the lungs to the blood. Patients that develop hypoxia require 

supplemental oxygen. For those who develop significant hypoxia (and airway edema), 

intubating the patient with an endotracheal tube and placing them on a ventilator that 

delivers positive pressure ventilation may be required. 





Slide 26 



What Toxic Gas Did He Inhale 


Chlorine 

26 

This case illustrates a typical finding from a severe chlorine gas exposure. This is a 

typical chest X-ray picture of chemical lung injury response: the presence of fluffy white 

infiltrates bilaterally is consistent with non-cardiogenic pulmonary edema or lung injury – 

i.e. not from fluid overload or heart failure. 

There are a number of medical conditions where the lungs become congested with fluid. 

The chest xray reveals the presence of infiltrates which take on a whitish appearance as 

opposed to the black radiographic appearance that appears with clear lung fields. If the 

lung congestion is thought to be from a failing heart, this is usually referred to as 

pulmonary edema. When the heart is not the culprit, the edema (or fluid congestion) is 

thought to be non-cardiogenic. An overwhelming infection can cause a non-cardiogenic 

edema. Consequential gas inhalation that results in a diffuse injury may also take on the 

appearance of non-cardiogenic edema. 

The radiograph on the slide has the appearance of a toxic gas exposure that may result 

after exposure to a number of toxic gases discussed in this presentation including 

chlorine, phosgene and methyl isocyanate. 





Slide 27 




Mixing together which of the following is most likely to 

form chlorine gas 

1. Ammonia and acidic toilet bowl clearer 

2. Bleach and acidic toilet bowl clearer 

3. Cyanide and bleach 

4. Acidic toilet bowl clearer and a dirty toilet 

5. Unable to make chlorine gas in the house 


27 

. 





Slide 28 



Dangerous Mixture 


28 

Chlorine gas exposures are probably the most common toxic gas exposure we see in 

the emergency department. The most common chlorine exposure we encounter 

involves the mixture of bleach (sodium hypochlorite) and an acid (toilet bowl cleaner). 

These two household chemicals are sometimes mixed together – either in an attempt to 

strengthen the disinfection process or at times when the chemicals are separately 

discarded into a common disposal reservoir such as a toilet or bathtub. The combination 

of sodium hypochlorite and acid produces chlorine gas and water. Other large scale 

chlorine exposures occur when chlorine is inadvertently released at a swimming pool 

during a misstep in the swimming pool disinfection process. 





Slide 29 



Chlorine Gas 

• Multiple Uses 

– Manufacturing of non -agricultural 

chemicals 

– Pulp and paper industry 

– Commercial & household bleaching 

agents 

– Water purification & waste treatment 

• 1998 US production > 14 million 

tons 

– Shipped as liquefied compressed 

gas 


29 

Chlorine is among the 10 most produced chemical in the US; in 1998, US production 

exceeded 14 million tons. Today, it is used for nonagricultural chemical manufacturing - 

including the production of chlorinated hydrocarbons (CCl4-carbon tetrachloride, vinyl 

chloride, chloroform) - pulp and paper industry as an oxidizing bleaching agent; as 

commercial and household bleaching agents; & in water purification and waste treatment 

systems as a disinfectant. Similar to ammonia, chlorine is shipped in large quantities 

over long distances as a liquefied compressed gas. 





Slide 30 



Chlorine: Physical Properties 

• Green -yellow, pungent gas 

• Low odor threshold; 

moderate warning properties 

• Intermediate water solubility 

• Boiling point –31 oF 

• Vapor density 2.5 (heavier than 

air) 

• Reacts explosively with many 

compounds 

http://www.amazingrust.com/Experiment 

show_to/Images/Chlorine_gas.jpg 


30 

Chlorine is a gas at standard temperature and pressure. Its presence is recognizable by 

a yellow-green color and pungent odor. Its vapor density is 2.5 (2.5 times as heavy as 

air). 

Chlorine has intermediate water solubility. Its solubility is between that of ammonia and 

phosgene (300 times less soluble than ammonia). As such, it can cause upper and 

lower airway symptoms after exposure. 

Though it has a low odor threshold of 3 ppm, the noxious odor does not necessarily 

serve as a reliable warning. Irritative symptoms can occur after exposure to chlorine gas 

at 1ppm for several hours which would be below the odor threshold (i.e. one would 

develop irritation prior to detecting the chlorine odor). 

Chlorine is a very reactive substance. When released, it does not exist for long in the 

molecular gas (Cl 2 ) form, but combines – often explosively – with other compounds. 





Slide 31 



Chlorine: Clinical Effects 

• Intermediate water -solubility 

• Low concentrations: 

– irritant to eyes, nose, throat, 

upper respiratory tract 

• Higher concentrations: 

– acute pulmonary edema, 

chemical pneumonitis 

• Chronic sequelae: 

– RADS 

Cl 2 + H 2 O ↔ HCl + HOCl 

http://www.aliciapatterson.org/APF1403/Borg/Borg04.jpg 


31 

The types of symptoms associated with a chlorine gas exposure are determined in part 

by chlorine’s intermediate water solubility. At lower concentrations chlorine exposure 

results in upper airway irritation and usually serves as a warning, preventing continued 

voluntary exposure. People complain of mucous membrane irritation: watery eyes, 

corneal irritation, runny nose, throat irritation, wheezing, and cough. 

However, at relatively low concentration, mild symptoms may be tolerated to some 

extent. If the exposed individual does not leave the source of exposure, continued low 

level exposure may ultimately increase the delivered dose, since dose is the product of 

both concentration and time. Continued low does exposure may result in a delayed 

onset of lower respiratory symptoms and potential injury to the lower respiratory tract, 

with bronchospasm-associated wheezing and inflammation. 

Similar to what may occur after methyl isocyanate exposure, RADS may also develop 

after chlorine exposure. 

Chlorine gas dissolves in water to form hydrochloric acid and hypochlorous acid. 

Hypochlorous acid subsequently dissociates into hydrochloric acid and oxygen free 

radicals, prolonging and exacerbating the injury. 

A chemical pneumonitis refers to the pneumonia (lung injury) that develops after certain 

chemical exposures. Unlike a bacterial pneumonitis, the chemical pneumonitis is not 

the result of an infection but is the direct result of the chemical injury to the lung tissue. 

Since it is not caused by in infectious agent, antibiotic treatment is not needed. 

The picture is a depiction of a World War I training poster emphasizing the steps soldiers 

could take (awareness, proper use of personal protection equipment) in response to the 

threat of a gas attack. 





Slide 32 



Chlorine: 1st Successful Chemical 

Warfare Agent, WW I 

Wind -borne Chlorine Attack, WWI 

http://www.germannotes.com/hist_ww1_poison.jpg 


Chlorine Gas Respirators 

32 

The first successful use of a gas as a chemical warfare agent in modern times was the 

German canister deployment of chlorine at the (Second) Battle of Ypres (Belgium) in 

April 1915. 168 tons of chlorine gas were released from 5700 canisters, resulting in 

10,000 French troops being affected (50% mortality) and resulting in a 4 mile breach in 

the front lines, of which the Germans were unprepared to take advantage. 

The British retaliated with chlorine at the Battle of Loos (Belgium) in September 1915, 

but unfavorable winds minimized the impact of that attack. 

Chemical warfare preparation at that time included 1) protective devices for the troops 2) 

development of toxic gases armamentarium 3) improvement in delivery system. 





Slide 33 



Chlorine from Train Accident (Graniteville, 

SC; Jan 6, 2005 02:40) 

http:// www.hazmatteam.com 


33 

Much more recently, this train derailment of freight cars containing chlorine 

demonstrates current vulnerabilities and potential threats from this compound. In this 

2005 incident, as the result of an improperly-aligned switch, a Norfolk Southern freight 

train was diverted onto a track, striking a parked train. One of three 90 ton chlorine 

tankers ruptured, releasing gas for ¼ to ½ mile in all directions (light wind). 

Note that this accident, like so many industrial accidents, occurred in the middle of the 

night. While that may hinder communications and response because of staffing and the 

presence of fewer bystanders, this timing may also decrease casualties because of 

fewer people being in –or traveling through – the area. The magnitude of the event was 

also minimized both by single tank rupture and the cooling of contents by rapid 

expansion. 

The picture shows an aerial view of the crash scene involving a road, a parking lot and 

power lines. 





Slide 34 



Consequences of Graniteville Train 

Accident (MMWR January 28, 2005) 

• 9 deaths 

– 1 train engineer, 6 mill workers, 

1 in home, 1 in truck 

• 529 sought medical care 

– 69 hospitalized, 11 critical 

– 18 were treated at area physicians ’ offices 

• 5,400 evacuated in 1 mile radius of crash 

• Initial report : "sodium nitrate" 

• Chlorine was not reported to ED for 1 hour 


34 

As the result of this derailment and chlorine release, over 5000 people were evacuated, 

500 sought medical attention, 69 were hospitalized and there were 9 deaths. Of interest 

the initial report detailing the nature of the release was erroneous and misleading. 





Slide 35 



Chlorine Transport in the US 

Rail transportation of chlorine and other toxic gases is 

common in highly populated cities 

 

 

 


35 

This scary-looking photo depicts the transport of a freight car loaded with chlorine gas 

making its way through our nation’s capital, literally in sight of the U.S. Capital. The 

impact of disruption of this railcar (equivalent to the release from the Graniteville SC 

accident) in this large, crowded city would be severe. Since this photo was taken in 

2004, hazardous rail transportation through Washington, DC has been curtailed 

precisely because of this potential transportation threat and the inability to contain this 

danger without rescheduling freight routes of hazardous chemicals. 

Making such route change carries its own significant economic and 

commerce/scheduling implications of re-routing. The decision in Washington D.C. was 

contentious, even post – 9/11. Rerouting of hazardous substances has been limited in 

scope and does not apply to most other U.S. cities. This vulnerability continues to be a 

major impediment to planning for all communities. 





Slide 36 



Chlorine Gas Attack by Truck Bomber 

Kills Up to 30 in Iraq 

BAGHDAD, April 6 (NY Times) — A 

suicide truck bomb loaded with 

chlorine gas exploded in Ramadi 

on Friday, killing as many as 30 

people, many of them children, a 

security official said. 

The explosion burned victims ’ lungs, 

eyes and skin. Dr. Ali Abdullah 

Saleh, of the main Ramadi 

hospital, said 30 people had been 

admitted with shrapnel wounds 

and 15 had been sent to a second 

hospital in the city. He said 50 

people had been admitted for 

breathing problems . 


36 

Actual terrorist uses of chlorine have occurred during the Iraqi War. In Iraq in 2007, 

terrorist groups began to use suicidal truck bombs loaded with chlorine. Since this time 

chlorine canisters have been incorporated into several improvised explosive device 

(IED) bombings. 

The news photograph shows the remains of the car bomb. The narrative describes the 

water-soluble irritant symptoms experienced by the victims. There were as many people 

injured by the chlorine gas as there were by shrapnel. 





Slide 37 



Phosgene: Cl 2 C=O 

• Used in the manufacture of 

– Organic chemicals: dyestuffs, isocyanates 

– Plastics 

– Insecticides 

– Pharmaceuticals 

• 80% used for isocyanate production 

• US production: estimated 1 million tons/year 

• Also formed as a combustion product when chlorine - 

containing compounds are burned 


37 

Phosgene is a common chemical intermediate used in the manufacture of organic 

chemicals (dyestuffs, isocyanates), plastics and polyurethanes, insecticides, and 

pharmaceuticals. 80% of phosgene production is used for isocyanate manufacture. 

Phosgene is also a combustion product, potentially produced anytime a chlorinated 

product (e.g. plastic) is burned. 

A chlorinated compound as used here is a hydrocarbon with chlorine substitution(s). 

Many of these compounds are heavily used in industry. When burned, such chlorinated 

compounds as methylene chloride and chloroform release phosgene. 





Slide 38 



• Synthesized in 1812 

• First used in WWI against 

the British at Ypres, 

Belgium (December 1915) 

Phosgene: History 


38 

Phosgene was first synthesized in 1812. During WWI, phosgene was extensively used in 

gas warfare. Its first wartime use was in Dec 1915 when the Germans shelled British 

troops with 88 tons of phosgene. This one attack resulted in ~1100 casualties and 120 

deaths. 

The top picture depicts buried gas cylinders used in attacks. The bottom picture is of a 

British machine gun crew in CG (referring to phosgene) helmets (site reported as Battle 

of Somme, July 1916, the bloodiest day of the war for the British Army). 





Slide 39 



Phosgene: Community Threat 

Assessment 

• 99.9% of production is 

“used on-site” 

• Storage and transport as 

liquefied compressed gas 

http:// www.chemicaldesign.com/Phosgene.htm 


39 

Ammonia and chlorine are transportation, as well as fixed facility threats, given the need 

to move large volumes of these chemicals to their industrial sites. In contrast, the threat 

of phosgene is mostly limited to a fixed facility. More then 99% of phosgene production 

is used in the manufacture of other chemicals within a plant boundary, 





Slide 40 



Phosgene 

• BASF Plant Ascension 

Parish, LA 

– 1981: Plant operator killed 

– 1982: 28 workers injured 

– 1986: phosgene plume 

over unpopulated parts 

of Ascension Parish 

http://commons.wikimedia.org/wiki/Image:Map_of 

_Louisiana_highlighting_Ascension_Parish.svg 


40 

During the 1980s there were several releases of phosgene from an industrial plant in 

Ascension Parish, LA. During one release the plant operator was killed and during 

another release, 28 workers were injured. During another event, phosgene was released 

with the wind carrying a plume outside the plant, fortunately over an unpopulated area. 

Ascension Parish (shown in red in the map of Louisiana on the slide) accounted for ~1/4 

of all the TRI (Toxic Release Inventory) chemical releases from the 64 parishes in LA at 

that time. A very small fraction of that 120,000,000 pounds was phosgene (1,493 

pounds). Despite the small amount, the local area effect of a release is still significant. 





Slide 41 



Phosgene: Physical Properties 

• Colorless gas with odor of musty hay 

• Higher odor threshold; poor warning properties 

• Low water solubility 

• Boiling point 8.2 ºC 

• Vapor density 3.5 (heavier than air) 


41 

Phosgene is a highly reactive gas of historical interest and current industrial importance. 

Because of its low water solubility, there are no immediate irritive effects to serve as 

warning properties of exposure. It is colorless and described as having a “musty hay” or 

“green corn” odor. The odor threshold is above the concentration that would result in 

lower airway & lung toxicity.; thus this compound has inadequate warning properties. It 

is a gas at room temperature with a vapor density 3.5 times that of air. As mentioned 

earlier, when shipped off-site, it is in liquid form in pressurized steel cylinders. 





Slide 42 



Phosgene 

Odor threshold: 

0.5 - 1.5 ppm 

10 min AEGL -2: 

0.60 ppm 

10 min AEGL -3: 3.6 

ppm 


42 

The colorless gas, phosgene, has the odor of moldy hay or green corn. However, 

recognition of odor is reliable only around a concentration of 1.5 ppm, a concentration at 

which injury is already occurring. 

Severe, but delayed-onset, pulmonary injury can be expected after a relatively short 

duration of exposure at levels that may not be appreciated by smell. Additionally, 

olfactory fatigue can occur, further impairing odor recognition. 

AEGL-2 is the concentration above which exposure would be expected to result in 

increasingly severe symptoms as exposure continued, with impairment of self-rescue. 

Above AEGL-3 concentrations, life-threatening symptoms are expected. 

Olfactory fatigue is a common, normal experience. It is an adaptive response in humans 

– to both noxious and non-noxious agents. As an example, the aroma of fresh-baked 

bread is more noticeable when first entering a room than several minutes later. With 

some chemical agents, it is thought that the cellular toxicity of the compound itself (e.g. 

hydrogen sulfide) contributes to the loss of odor recognition. 

The posters on the slide were used in World War II military training to increase awareness of 

soldiers, medical providers, and the general community of various aspects of chemical warfare. 





Slide 43 



Phosgene: Clinical Effects 

• Limited initial symptoms 

– Irritation of eyes, nose, upper airways 

– Higher concentrations cause airway spasm 

• Low water solubility – slow hydrolysis to HCl 


43 

Because of its low water solubility, a victim will continue to inhale phosgene, with 

increased contact time deeper into the lungs, causing lower airway and lung damage. 

Immediate symptoms are usually mild and are due to irritation of the mucous 

membranes from slow release of hydrochloric acid as shown in the chemical equation on 

the slide. These symptoms include eye irritation, throat irritation, and mild cough. 





Slide 44 



Phosgene: Delayed Effects 

• Latent development of pulmonary edema 

– Onset 1 to 24 hours after exposure 

– Pulmonary function abnormalities 

– May be fatal 

• Chronic airway disease 

COCl 2 

+ 2 R-NH 2 

CO(NH-R) 2 

+ 2HCl 


44 

Delayed onset symptoms are due to deep tissue damage and associated with fluid 

collection in the lungs and lung function abnormalities. The fluid collection can occur 

within minutes, but usually there is a latent period of hours; symptoms can be delayed 

up to 72 hours. 

Following significant exposure, death due to pulmonary edema can occur after a delay of 

24-48 hours. 

Exposed persons can have chronic airway disease with permanently abnormal 

pulmonary function. 





Slide 45 



Phosgene: Delayed Lung Injury 

6 hrs post-exposure 

10 hrs post-exposure 


45 

These Chest X-ray pictures of delayed-onset pulmonary edema after phosgene 

exposure shows the progression of peripheral pulmonary infiltrates over time, as is 

typical of non-cardiogenic pulmonary edema. 

Chest X-ray appearances can lag behind clinical symptoms, but the accumulation of 

lung water – and inflammatory cells – as depicted by the increased whiteness of the 

normally black lung fields on X-ray is one indication of the degree of injury occurring in 

this case. 





Slide 46 



Hydrofluoric Acid (HF) 

• HF is used for a variety of industrial 

processes and consumer products (dilute), 

including 

– Catalyst in oil refineries 

– Manufacture of silicon semiconductor chips 

– Separating uranium isotopes 

– Etching glass or enamel 

– Cleaning brass, crystal and as a rust 

remover 

• Production in U.S. is < 1 million tons/year 

• Transported as pressurized anhydrous 

liquid by rail 

http:// www.viewimages.com/Search.aspx 

mid=1307009&epmid=1&partner=Google 


46 

Hydrofluoric Acid (HF) is a relatively low production volume chemical in the US, but it 

has multiple industrial and household uses. Along with hydrogen sulfide (a cellular 

poison somewhat similar to cyanide), it is a major concern at oil refineries. It is also 

used in the semiconductor industry, and for a number of other specialty purposes listed 

on the slide. HF (and related compounds) are available in dilute solution (




Slide 47 



HF: Physical Properties 

• Colorless, non -flammable, fuming liquid or gas with 

irritating odor 

• Low odor threshold; good warning property 

• Highly water soluble - with release of heat 

• Weak acid 

– Not highly dissociated, but penetrates tissue well 

• Boiling point 20 °C 

• Vapor density 0.7 


47 

HF is a very toxic substance, but at the same time it is a relatively weak acid. It has a 

low odor threshold and is irritating as a concentrated vapor, providing good warning 

properties of exposure. At the same time, dermal exposure to dilute solutions does not 

cause immediate symptoms, as do other acids. 





Slide 48 



HF: Clinical Effects 

• Highly corrosive depending on concentration and 

irritating to all tissues 

• Onset of pain and skin changes may be delayed for 

hours with dilute (






Texas City, TX Industrial Accident 

Releasing HF (October 31, 1987) 

• ~30,000 pounds of hydrofluoric acid leaked from an HF 

alkylation reactor drum when a 50 foot long convection unit 

was dropped on the vessel 

• Vapors emitted under pressure for 2 hours 

• Estimate of AEGLS 3 at ~3/4 mile away 

• ~4000 residents evacuated for 3 days 

• >1000 people to hospital with skin, eye, nose/throat irritation 

and pulmonary symptoms 

• No fatalities 


49 

The last gas we will cover in this module is hydrofluoric acid (HF). In concentrated form, 

HF is a gas. The largest industrial accident related to HF occurred about 20 years ago 

when a piece of equipment was dropped by a crane onto a reactor vessel at an oil 

refinery in TX, releasing HF under pressure. The leak continued for 2 hours. It is 

estimated that life-threatening concentrations of the gas (AEGL 3) extended nearly one 

mile from the site. More than 1000 people were evaluated for symptoms and 4000 

residents were evacuated for 3 days, at which point the leak had been plugged and 

remaining diluted HF drained. 





Slide 50 




50 

The importance of plant security, “hardening” of containment measures, and minimizing 

on-site storage of TICs is illustrated by this example of a chemical plant which 

maintained 500,000 lbs of Hydrogen Fluoride on-site (year 2004 -mean maximum 

amount on a daily basis). 

This Google map aerial photo identifies an industrial plant in Oakland, CA. This amount 

of HF is ~10 times the amount released in the Texas City accident. 





Slide 51 




51 

An intentional (or accidental) release of 10 times the amount of HF released in the Texas 

City accident, given “favorable” wind conditions, would impact a major highway and large 

sports arena, or industrial and residential property. While this could be mitigated by 

early communication of a “shelter-in-place” order, that would not be helpful to attendees 

at the open-air coliseum less than ½ mile away. 





Slide 52 



• Community threat 

assessment 

• Emergency response 

planning 

• Prevention through zoning 

and/or substitution of less 

hazardous processes 

HF: Preparedness 


52 

Prevention and planning may decrease the need for mitigation and recovery. All of 

these aspects are important and should be done in partnership with other public health, 

responder, industry, citizen, and government groups, using the expertise of each. 





Slide 53 



Summary: Toxic Gas Characteristics 

AGENT 

PHYSICAL PROPERTIES 

EXPECTED CLINICAL EFFECTS 

H 2 

O 

Solubility 

Odor / 

Warning 

Vapor 

Density 

Mucosal / 

Upper Airway 

Lower 

Airway 

Systemic 

MIC 

High 

Pungent / 

Inadequate 

1.4 

Yes 

Possible 

No 

NH 3 

High 

Pungent / 

Good 

0.5 

Yes 

Possible 

No 

Cl 2 

Interm . 

Pungent / Fair 

2.5 

Yes 

Yes 

No 

COCl 2 

Low 

Mown Hay/ 

Inadequate 

3.5 

Unlikely 

Yes 

No 

HF 

High 

Pungent / 

Good 

0.7 

Yes 

Possible 

Electrolyte & 

Cardiac 

Rhythm 


53 

This table summarizes some of the material covered up to this point. 

The major feature to remember is that for those agents with high water solubility, 

mucous membrane (eye, nose, throat) and upper airway symptoms would be expected 

to predominate, while low water solubility gas exposure victims will often demonstrate 

a predominance of lower respiratory symptoms, except in cases with high dose (amount 

x time) exposure. 

Certain agents (such as HF) can cause systemic effects that may be more important 

than the local irritant/corrosive effects. 





Slide 54 



Treatment for Irritive Gas Exposure 

• Remove from exposure 

• Irrigation of eyes or skin if 

involved 

– Extensive decontamination 

usually not necessary unless 

liquid exposure 

• Oxygen 

• Nebulized beta-agonists (e.g. 

albuterol ) for wheezing or 

dyspnea 


54 

Despite the significant toxicity of all of these gases, there are no specific antidotes to 

reverse the effects. However, there are steps and treatments that are important for 

management of these patients. 

As with almost all toxic situations, removal from ongoing exposure – with attention to 

safety of rescuers – is most important. 

Water-soluble agents will lead to significant eye symptoms and appropriate irrigation of 

exposed tissue is very important for both comfort and long-term outcome. However, 

extensive efforts at decontamination (e.g. stripping all clothing and full “wet decon”) is 

usually inappropriate for gas/vapor exposure. In an industrial setting with exposure to 

liquid, full decon may be important. Certainly HazMat technicians would require 

chemical protective clothing and self-contained breathing apparatus to enter such a 

scene. 

Many of these compounds cause hypoxia (directly or indirectly), so oxygen 

administration is important; administration of albuterol (a bronchodilator) will address 

some of the bronchial hyper-reactivity common to these chemical exposures. Once 

stabilized, corticosteroids may also be appropriate in modifying the inflammatory 

pulmonary response. 





Slide 55 



Special Considerations 

• Consider adding sodium bicarbonate to nebulizer in 

chlorine gas exposures 

• Intravenous and inhaled calcium gluconate, and 

continuous cardiac monitoring are important for 

hydrogen fluoride exposure 

• Observe patients for late pulmonary effects, 

particularly in those with severe early symptoms 


55 

There are some situations where specialized treatment may provide some incremental 

benefit. As an example, the use of sodium bicarbonate in nebulizer treatments may 

provide some treatment for the acid generation following chlorine inhalation. 

In other situations, specific treatment is definitely indicated. As examples, multiple 

administrations of calcium gluconate may be necessary depending on the dose and 

delivery route of a hydrogen fluoride exposure; and continued observation of relatively 

asymptomatic patients for delayed-onset pulmonary symptoms is indicated following 

phosgene exposure. 

The importance of accurate identification of the offending agent and 

monitoring/treatment of “special agents” should be emphasized (and pointed out on the 

following summary slide). This would also be an opportunity to remind the participants of 

the importance of correlating or comparing identification information provided, with the 

clinical toxidromes observed. As an example, hydrofluoric acid exposure is often initially 

misidentified as hydrochloric acid exposure, but the relative predominance of systemic 

effects with the former vs. dermal effects should point out the error. 





Slide 56 


Questions 


56 





Module Three Summary 

This module presented a detailed overview of chemical compounds that are produced in large 

quantities as part of America’s industrial complex. Many of these compounds are amenable for 

use as large scale terrorist weapons and may be released in the form of toxic gases. Exposure 

to these toxic gases will create serious health implications for its victims. The clinical symptoms 

created by exposure to toxic gases will be determined by the dose (concentration of chemical 

and duration of exposure), the unique properties of the agent (e.g. water solubility), and the 

underlying health status of the exposed individual. Clinical management of these patients 

includes immediate removal from the exposure and the initiation of appropriate management 

strategies. Care must be taken to ensure that rescuers and other first receivers do not become 

victims as well. Because of the major role these compounds play in modern industry, community 

hazard vulnerability assessment using the expertise of a variety of responsible individuals within 

the public health, emergency planning, responder, medical care provider, industry and lay public 

is critical to prepare for accidental and intentional releases. 





Module Four 

Cyanide & Fumigants - Administration Page 

Cyanide and fumigants constitute a threat to the general population because they are easily 

weaponized, highly toxic when inhaled, and widely available due to their extensive use in the 

agriculture and pest-control industries. While accidental exposure is not uncommon, there is 

significant concern about their potential use as weapons of mass destruction. Though public 

attention has focused on past incidents of drug tampering, a more substantial danger is these 

agents’ suitability for dispersal as a gas through ventilation systems. 

Duration 

45 minutes 


This module reviews commercial applications, characteristics, and treatment guidelines relating 

to hydrogen cyanide gas and to the three most common fumigants regulated by the US 

Department of Agriculture: Vikane (sulfuryl fluoride), methyl bromide, and phosphine. 


• Recognize and provide appropriate initial therapy for individuals 

exposed to cyanide and to fumigant gases. 


Resources 

• Indicate the sources and uses of cyanide and fumigants 

• Describe therapies used to treat cyanide poisoning 

• List the four most common fumigant gases 

• Describe the clinical effects of exposure to these gases 

• Explain how to treat victims exposed to these gases 







[Enter the instructor to participant ratio(e.g., 1:25).] 


1. Sperry P. Al-Qaida terrorists to gas US subways DHS memo warns 

of device that uses cyanide to asphyxiate its victims. WorldNetDaily, 

25 November 2003. 





2. Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide 

concentrations in victims of smoke inhalation. NEJM 1991;325:1761- 

1766. 

3. BBC News. Romania’s poison dump. May 19 2000. Accessed Dec 

2008 from: 

http://news.bbc.co.uk/1/hi/programmes/correspondent/755780.stm 

4. Bogle RG, Theron P, Brooks P, Dargan PI, Redhead J. Aluminium 

phosphide poisoning. Emerg Med J. 2006 Jan;23(1):e3. 

5. Burgess JL. Phosphine exposure from a methamphetamine laboratory 

investigation. J Toxicol Clin Toxicol. 2001;39(2):165-8. 

6. Burgess JL, Morissey B, Robertson WO. Fumigant related illnesses: 

Washington State’s five year experience. J Toxicol Clin Toxicol 

1998: 36(5):465 (abstract). 

7. Burkhart K. Methyl Bromide and Other Fumigants, in Goldfrank’s 

Toxicological Emergencies; Goldfrank LR, Flomenbaum N, Hoffman 

RS, et al (eds.) McGraw-Hill Professional, 8th edition, 2006. 

8. Centers for Disease Control and Prevention. Epidemiologic Notes and 

Reports Fatalities Resulting From Sulfuryl Fluoride Exposure After 

Home Fumigation—Virginia. MMWR 1987;36(36):602-604,609-611. 

9. Centers for Disease Control and Prevention: National Institute for 

Occupational Safety and Health. NIOSH Alert: preventing phosphine 

poisonings and explosions during fumigation. NIOSH Publication No. 

99-126;1999. Accessed Dec 2008 from: http://cdc.gov/niosh/99- 

126.html 

10. Centers for Disease Control and Prevention: Agency for Toxic 

Substances and Disease Registry. Medical Management Guidelines 

for Phosphine. Accessed Dec 2008 from: 

http://www.atsdr.cdc.gov/mhmi/mmg177.html 


Occupational Safety and Health. Acetonitrile. NIOSH Pocket Guide to 

Chemical Hazards. Accessed Dec 2008 from: 

http://www.cdc.gov/niosh/npg/npgd0006.html 


Occupational Safety and Health. Acrylonitrile. NIOSH Pocket Guide to 

Chemical Hazards. Accessed Dec 2008 from: 



Occupational Safety and Health. Cyanogen Chloride The Emergency 

Response Safety and Health Database. Accessed Dec 2008 from: 

http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_2975003 

9.html 


Occupational Safety and Health. NIOSH Pocket Guide to Chemical 

Hazards: Sulfuryl fluoride. 2005. Accessed Dec 2008 from: 







Occupational Safety and Health. Phosphine. The Emergency 

Response Safety and Health Database. Accessed Dec 2008 from: 

http://www.cdc.gov/niosh/ershdb/EmergencyResponseCard_2975003 

5.html 

16. Cyanokit package insert. Access Dec 2008 from: 

http://www.cyanokit.com 

17. Dunea G. Death over the counter. Br Med J 1983; 286:211-2. 

18. Eckstein M, Manistalco PM. Focus on smoke inhalation – the most 

common cause of acute cyanide poisoning. Prehosp Disast Med 

2005;21(2):s49-s55. Accessed Dec 2008 from: 

http://pdm.medicine.wisc.edu/21-2%20PDFs/eckstein.pdf 

19. Ellison NM, Byar DP, Newell GR Special report on Laetrile:the NCI 

Laetrile review. Results of the National Cancer Institute’s retrospective 

Laetrile review. NEJM 1978;299:549-552. Accessed Dec 2008 from: 

http://content.nejm.org/cgi/content/abstract/299/10/549 

20. Environmental Protection Agency. Overview of the Use and Usage of 

Soil Fumigants, 2005. Accessed Dec 2008 from: 

http://www.epa.gov/oppsrrd1/reregistration/soil_fumigants/soil_fumiga 

nt_use.pdf 

21. Ferrari LA, Arado MG, Giannuzzi L, et al.. Hydrogen cyanide and 

carbon monoxide in blood of convicted dead in a polyurethane 

combustion: a proposition for the data analysis. Forensic Sci 

International 2001;121(1-2):140-143. 

22. Gill JR, Goldfeder LB, Stajic M. The Happy Land homicides: 87 

deaths due to smoke inhalation. J Forensic Sci 2003;48(1):161-163. 

Accessed Dec 2008 from: 

http://www.astm.org/JOURNALS/FORENSIC/PAGES/JFS2002227_4 

81.htm 

23. González ER. Cyanide evades some noses, overpowers others. 

JAMA 1982 Nov 12;248(18):2211. 

24. Gupta, S. Maryland Teen Facing First Degree Murder Charges For 

Poisoning Friend. CNN, American Morning. Originally broadcast: Jan 

10, 2003. Transcript accessed Dec 2008 from: http://wwwcgi.cnn.com/TRANSCRIPTS/0301/10/ltm.12.html 

25. Holstege CP, Isom GE, Kirk MA, et al. Cyanide and Hydrogen Sulfide. 

In: Flomenbaum NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin 

N, Nelson LS. Goldfrank’s Toxicologic Emergencies, 8th Edition. 

McGraw-Hill. New York, NY. 2006. 

26. Horowitz BZ, Albertson TE, O'Malley M, Swenson EJ. An unusual 

exposure to methyl bromide leading to fatality. J Toxicol Clin Toxicol. 

1998;36(4):353-7. 

27. Keim MJ: Terrorism involving cyanide: The prospect of improving 

preparedness in the prehospital setting. Prehosp Disast Med 

2006;21(2):s56–s60. 





28. Lance P. 1000 Years For Revenge: International Terrorism and the 

FBI: The Untold Story. HarperCollins Publishers, 2004. 

29. Layton, Deborah. Seductive Poison. Doubleday/Anchor. 1998. 

30. Lee J, Mukai D, Kreuter K et al. Potential interference by 

hydroxocobalamin on cooximetry hemoglobin measurements during 

cyanide and smoke inhalation treatments. Ann Emerg Med 

2007;49(6):814-6. 

31. Litovitz TL, Klein-Schwartz W, White S, et al. 2000 Annual report of 

the American Association of Poison Control Centers Toxic Exposure 

Surveillance System. Am J Emerg Med 2001;19(5):337-395 

[Appendix, Case #175]. 

32. Madrzykowski D, Bryner N, Kerber SI. The NIST Station Nightclub 

Fire Investigation: Physical Simulation of the Fire. Fire Protection 

Engineering; 2006 Summer. Accessed Dec 2008 from: 

http://www.fpemag.com/archives/article.aspissue_id=37&i=245 

33. Michnea A, Gherheş, J. Impact of metals on the environment due to 

technical accident at aurul baia mare, romania. Int J Occ Med Environ 

Health. 2001;14:255-59. 

34. Montreal Protocol. Wikipedia. Access Dec 2008 from: 

http://en.wikipedia.org/wiki/Montreal_Protocol 

35. Mui, YQ. Maryland Teen Gets Life For Poisoning Friend. Washington 

Post. July 21, 2004. Accessed Dec 2008 from: 

http://www.washingtonpost.com/wp-dyn/articles/A114-2004Jul20.html 

36. National Institute for Occupational Safety and Health (NIOSH). 

Hydrogen Cyanide IDLH Documentation. Accessed Dec 2008 from: 

http://www.cdc.gov/Niosh/idlh/74908.html 

37. North Dakota Department of Agriculture. Timeline for sodium cyanide 

case. February 23, 2005. Accessed Dec 2008 from: 

http://www.agdepartment.com/2005Press/TimelineSodiumCyanideCa 

se2-11-05.pdf 

38. Olsen, Gregg. Bitter Almonds. St. Martin’s True Crime. 2006. 

39. Palatnick W, Tennebein M. Methyl bromide poisoning treated with 

hemodialysis. J Toxicol Clin Toxicol 1998; 36(5):464. 

40. Peddy SB, Rigby MR, Shaffner DH. Acute cyanide poisoning. Pediatr 

Crit Care 2006;7(1):79-82. 

41. Pesticide Action Network (PAN) Pesticide Database. Access Dec 

2008 from: http://www.pesticideinfo.org/ 

42. Phosphine. Wikipedia. Accessed Dec 2008 from: 

http://en.wikipedia.org/wiki/Phosphine 

43. Polk, J. Jones plotted cyanide deaths years before Jonestown. 


http://www.cnn.com/2008/US/11/11/jonestown.cyanide/ 






44. Regional Environmental Center for Central and Eastern Europe. 

Death of a river. The Bulletin 2000 9(2). Access Dec 2008 from: 

http://greenhorizon.rec.org/bulletin/Bull92/deathriver.html 

45. Sodium Thiosulfate at Drugs.com. Accessed Dec 2008 from: 

http://www.drugs.com/mmx/sodium-thiosulfate.html 

46. Sperry P. Al-Qaida terrorists to gas US subways DHS memo warns 

of device that uses cyanide to asphyxiate its victims. WorldNetDaily 

25 November 2003. 

47. Status Report for Fumigant Pesticides. Department of Pesticide 

Regulation, April 2003. Access Dec 2008 from: 

http://www.cdpr.ca.gov/docs/emon/methbrom/stat0403.pdf 

48. Sulfuryl fluoride. Wikipedia. Accessed Dec 2008 from: 

http://en.wikipedia.org/wiki/Sulfuryl_fluoride 

49. “The Gas Chamber”. Accessed Dec 2008 from: 

http://www.capitalpunishmentuk.org/gascham.html 

50. Tucker JB. Toxic Terror. Monterey Institute of International Studies. 

MIT Press, 2000. 

51. United States Army Center for Health Promotion and Preventive 

Medicine. Detailed Facts about Blood Agent Hydrogen Cyanide (AC). 

Accessed Dec 2008 from: http://chppmwww.apgea.army.mil/dts/docs/detac.pdf 

52. United States Fire Administration. “Fire Statistics”. Accessed Dec 

2008 from: http://www.usfa.dhs.gov/statistics/ 

53. Willers-Russo LJ. Three fatalities involving phosphine gas, produced 

as a result of methamphetamine manufacturing. J Forensic Sci. 1999 

May;44(3):647-52. 

54. Wilson B. The Rise and Fall of Laetrile, at Quackwatch.org; 2004. 

http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/laetrile. 

html 


















Module Four 

Icon Map 






instruction 





Slide 1 


Module Four 

Cyanide & Fumigants 


1 

Cyanide and fumigants constitute a threat to the general population because they are 

easily weaponized, highly toxic when inhaled, and widely available due to their extensive 

use in the agriculture and pest-control industries. While unintentional exposure can 

occur, the US Department of Homeland Security is concerned about their potential for 

use as weapons of mass destruction. Though public attention has focused on past 

incidents of drug tampering, a more imminent danger is these agents’ suitability for 

dispersal through forced air ventilation systems. 





Slide 2 

The components of the learning objectives can be summarized as: becoming familiar 

with the sources and uses of cyanide and fumigants, the clinical impact of exposure to 

these, and available treatment modalities. 





Slide 3 



• Cyanide 

– Salts (solids) 

– Gas 

• Fumigant gases 

Cyanide & Fumigants 

– Vikane (sulfuryl fluoride) 

– Methyl bromide 

– Phosphine 

Module Four – Cyanide & Fumigants 

3 

In 2003, the US Department of Homeland Security (DHS) issued a bulletin warning of 

the possibility of terrorists using ventilation systems to disperse cyanide gas. Although 

not part of the bulletin, fumigants could be similarly deployed. 

This module reviews commercial applications, characteristics, and treatment guidelines 

relating to cyanide and to the three most common fumigants regulated by the US 

Department of Environmental Protection (regulation/use) and the Department of 

Agriculture (application): Sulfuryl fluoride, methyl bromide, phosphine, and chloropicrin. 

Cyanide under standard temperature conditions is a gas and it is used as a gas in 

certain industrial uses, but it is widely available in salt (powdered) form as well. The 

fumigants are all gases and are stored in high pressure cylinders. 





Slide 4 



Cyanide 

• Notoriety well deserved 

• Historical relevance 

– Mass poisoning 

• Pharmaceutical terrorism 

• Weapon of Mass Destruction 


4 

Public conceptions of cyanide have been strongly influenced by its often fanciful 

depiction in popular culture (murder mysteries, TV show “24”, etc.) and through realworld 

crises (Tylenol tampering, Jonestown massacre, poisonings). Misconceptions 

regarding cyanide abound. Fictional depictions of cyanide usually refer to a white 

powder or clear liquid, smelling strongly of bitter almonds, that brings about almost 

instantaneous death when taken orally. As we will see through the course of this 

module, real-world scenarios involving cyanide challenge these preconceived notions. 





Slide 5 



Cyanide (CN): Properties 

• Small molecule (26 Dalton) 

• Boiling Point 27.7 °C 

• Colorless 

• Bitter Almonds Myth 

• Water soluble 


5 

Cyanide is commonly encountered in one of two forms: as a solid salt (sodium cyanide, 

potassium cyanide) or as a gas (hydrogen cyanide). While solid cyanide salts are usually 

white, in aqueous solution (ie. water soluble) or as a gas, cyanide is colorless. Its 

relatively low boiling point means that it would exist as a gas at room temperature unless 

kept in solution. Cyanide remains in aqueous solution at an alkaline (basic) pH. 

Hydrogen cyanide gas cannot be easily detected by its odor. The scent of bitter almonds 

is faint and many exposed people (who live to tell about it) do not report having smelled 

anything. 





Slide 6 



Cyanide: Two Common Forms 

Hydrogen Cyanide Gas 

Solid Cyanide Salts 

(sodium cyanide, 

potassium cyanide, 

calcium cyanide) 

Toxic when Inhaled 

Toxic when Ingested 


6 

This lecture will primarily be devoted to inhalation exposures to hydrogen cyanide gas 

because that constitutes the more significant threat. Hydrogen cyanide gas is readily 

absorbed through the lungs and results in rapid onset (seconds) after exposure and 

more severe clinical effects. 

The salt forms of cyanide (such as sodium cyanide) require dissolution in stomach water 

delaying the onset of symptoms after ingestion compared to when inhaled. Also, the 

kinetics of gastrointestinal uptake are slower than following inhalation. Thus symptoms 

following ingestion may be delayed about 20 minutes, as opposed to nearly immediately 

after inhalation. 

Sodium and potassium salts are widely available from chemical supply companies and 

industry. Calcium cyanide is sometimes used to clean the brass buttons used on 

traditional Korean costumes. 





Slide 7 



Generating HCN Gas from Salts 


7 

Using a simple chemical reaction, cyanide salts can be mixed with an acid (or even just 

with water which has some acid in it naturally) to produce hydrogen cyanide gas. 





Slide 8 



• Sources of cyanide (solid) 

Cyanide 

– Industrial applications (electroplating, hardening steel, 

mining, fumigation, …) 

– Sodium, potassium and calcium cyanide are all readily 

purchased on the internet 

• Other sources 

– Cyanogen chloride 

– Acetonitrile, acrylonitrile 

– Natural occurring cyanogens (laetrile) 


8 

Given its abundant legitimate uses in industry, cyanide, particularly in salt form can be 

easily purchased in a variety of forms – most commonly sodium cyanide, potassium 

cyanide, and calcium cyanide. 

Cyanide has many industrial applications and potential availability from many sources. 

Some of these include: 

1. Sodium and potassium salts are widely available from chemical supply companies and 

industry. 

2. Cyanogen chloride, also known as CK when used as a war agent, is a extremely toxic 

chemical compound with the formula CNCl; it is a colorless gas. 

3. Acetonitrile, CH3CN, is a colorless liquid and the simplest organic nitrile; it is widely used 

as a solvent. It can be metabolised to produce hydrogen cyanide if ingested. 

4. Acrylonitrile, CH2CHCN, is a pungent-smelling colorless liquid that often appears yellow 

due to impurities. It is an important monomer for the manufacture of useful plastics. 

5. Laetrile, or amygdalin, is a naturally occurring compound found in peach and apricot pits 

that when ingested, is metabolized by the body to cyanide. It was used in the past 

(1970’s) as an anticancer agent in Mexico, and is used by alternative practitioners as 

“vitamin B17” in the US. 





Slide 9 



Cyanide: Mechanism of Action 

• Readily enters cells 

• Inhibits mitochondrial 

respiration 


9 

Cyanide is a systemic poison with no single target organ. Cyanide acts by inhibiting 

enzymes within the mitochondria (or powerhouse) of all cells. This results in the 

complete arrest of cellular respiration and chemical asphyxiation of affected cells. In 

simple terms, the cells suffocate. The heart and CNS system, being the most oxygensensitive 

organs in the human body, are most affected by cyanide poisoning. 

Cyanide is an inhibitor of the enzyme cytochrome c oxidase (also known as aa3) in the 

fourth complex of the electron transport chain (found in the membrane of the 

mitochondria of eukaryotic cells.) It attaches to the iron within this protein and prevents 

oxygen from acting as the final electron acceptor in the chain. Thus the cell can no 

longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic 

respiration, such as the central nervous system and the heart, are particularly affected. 





Slide 10 



Cyanide 

Other Cytochrome Oxidase Inhibitors: 

• Hydrogen sulfide 

– “sewer gas” 

• Sodium azide 

– Component of airbags 

• Carbon monoxide 

– minor mechanism 


10 

There are other cytochrome oxidase inhibitors, such as hydrogen sulfide, sodium azide, 

and carbon monoxide. Exposure to these other cytochrome oxidase inhibitors, due to 

their similar mechanism of action, may produce systemic clinical effects similar to 

cyanide poisoning. Hydrogen sulfide, also called sewer gas, is found in manure pits, but 

also has use in industry. Sodium azide is a colorless azide salt commonly used in 

organic synthesis, and it is a component in many car airbag systems. Carbon monoxide 

is readily generated by burning organic matter. When a victim presents with rapid loss of 

consiousness that is considered to be related to an inhalational exposure, the likely of a 

“knock down gas” is raised. The differential diagnosis boils down to the following “knock 

down gases”: cyanide gas, hydrogen sulfide gas, carbon monoxide, and oxygendeficient 

air. 

Hydrogen sulfide, H2S, is colorless, toxic and flammable gas is partially responsible for 

the foul odor of rotten eggs. It is irritating and has good warning properties due to its 

sulfury odor; however at high concentrations this chemical’s odor paradoxically fades 

and poisoning is likely. 

Azide is the anion with the formula N 3 - ; Sodium azide is the sodium salt NaN 3 This latter 

compound is colorless and is a common reagent in organic synthesis, and is a 

component in many car airbag deployment systems because of its explosive nature (it 

forces out the airbag). 

Carbon monoxide, or CO, is a colorless, odorless gas that is produced during incomplete 

combustion of organic compounds. It inhibits mitochondria similarly to the way that CN 

does, but it has other more consequential toxic effects on the red blood cells. 

Poisoning by each is preventable with proper safety systems or personal protective 

equipment. 





Slide 11 



• Cyanide salts 

Cyanide: Toxic Quantities 

– Lethal dose: 200 -300 mg (3 mg/kg) 

• Hydrogen Cyanide (HCN) gas 

– Lethal dose: 50 -100 mg 

• 10 ppm for 2 -hours = headache 

• 100-200 ppm = death in 1 -hour 

• 200-300 ppm = death in several minutes 


11 

As previously mentioned cyanide is more readily absorbed and considerably more lethal 

in gaseous form. While 200-300 mg of constitute a lethal oral dose of cyanide salts, only 

50-100mg of hydrogen cyanide is needed to produce a similar effect. 





Slide 12 



Cyanide: Clinical Manifestations 

• “Gasp poison” 

• Central Nervous System 

– Headache, confusion, agitation, syncope, convulsions, 

coma, death 

• Cardiovascular 

– Tachycardia, hypertension 

– Bradycardia, hypotension 

– Cardiac arrest 

• GI 

– nausea, vomiting, abdominal pain 


12 

Cyanide is a systemic poison; there is no specific target organ. It is sometimes called a 

“blood agent” because it is carried by the blood for distribution to the body. As a result 

there is no reliable clinical “toxidrome” for low level cyanide poisoning; no specific 

constellation of signs and symptoms. The heart and central nervous system are 

generally most susceptible because they are the most oxygen-sensitive organs. Thus at 

high level exposures, coma and cardiac arrest make up the toxidrome. The word gasp 

poison suggests that when inhaled the onset is very rapid that the victim literally gasps 

for breath. 

CNS manifestations include syncope, or loss of consciousness, which rapidly resolves, 

though most of the time the patient does not rapidly recover and remains comatose. 

Cardiovascular manifestations include rapid (tachycardia) and (bradycardia), slow heart 

rates as well as high (hypertension) and low (hypotension) blood pressures. 

The term "blood agent" is a misnomer because these agents do not really affect the 

blood. Blood agents may act upon all tissues in the body once distributed by the blood. 





Slide 13 



Some possible suspects: 

• Hydrogen cyanide 

• Hydrogen sulfide 

• Carbon monoxide 

• Oxygen-deficient air 

Knock-Down Gases 


13 





Slide 14 



Cyanide: Onset of Symptoms 

Time to Onset of Symptoms 

• Cyanide salt and cyanide gas (HCN) 

– Minutes 

– Inhalation of gas >> ingestion >> dermal 

– Survival > 10 minutes, most likely will survive 

• All or Nothing 

• Aliphatic cyanogens & Natural cyanogens 

– Hours – must be metabolized 


14 

The amount of time until the onset of symptoms is relatively short – usually on the order 

of a few minutes – with both solid and gaseous cyanide exposure. Onset is faster for 

inhalation of hydrogen cyanide gas than for the ingestion of cyanide salts or for dermal 

exposures. Cyanide poisoning tends to be an all or nothing in terms of outcome; those 

who survive the first 10 minutes after the onset of symptoms will likely survive in the 

long-term. 

The salt forms of cyanide (such as sodium cyanide) require dissolution in stomach water 

delaying the onset after ingestion compared to when inhaled. Also, the kinetics of 

gastrointestinal uptake are slower than following inhalation, further explaining why it 

takes about 20 minutes to get sick after ingestion as opposed to nearly immediately after 

inhalation. 

Cyanogens are compounds that generate cyanide after metabolism. Examples include 

linamarin from cassava and amygdalin from peach pits (sold in the 1970’s and still today 

as Laetrile) 





Slide 15 



Cyanide: Diagnostic Testing 

• ABG 

– Anion gap metabolic acidosis 

• VBG 

– “Arteriolization ” of venous blood gas 

• Lactate 

– Elevated 

• Blood cyanide levels 

– Whole blood or serum 

– 2-3 day turn around time 


15 

The clinical laboratory can be useful in making the diagnosis of cyanide poisoning. Anion 

gap metabolic acidosis is usually present and is due to the presence of large amounts of 

lactate (L-lactate). 

Arteriolization of the venous blood gas may be present. That means that the arterial 

blood, when passing through the capillaries, does not have its oxygen removed by the 

tissues (since their mitochondrial electron transport chain is blocked by cyanide) and the 

blood passes into the venous system with lots oxygen. 

Blood cyanide levels from either whole blood or serum can also be obtained but these 

are usually performed outside the hospital setting and have a 2-3 day turnaround time. 

One characteristic of cyanide poisoning is the “arteriolization” of the venous blood gas. 

This is due to a very poor oxygen extraction ratio from the capillary blood as it passes 

from artery to vein, and a very high content of oxyhemoglobin in the venous blood. It is 

generally felt that O2 saturation on a venous blood gas (VBG) over 80% is suggestive of 

cyanide (or other mitochondrial enzyme) poisoning. One simple assessment for cyanide 

poisoning is to look at the color of the venous blood: arterial blood is bright red while 

venous blood should be deep red. Arteriolization is when the venous blood looks bright 

red like arterial blood. 





Slide 16 



Cyanide: Real World Scenarios 

• Battlefield 

• Mass Murder 

• Mass Suicide 

• Homicide 

• Pharmaceutical Terrorism 

• Environmental Terrorism 

• Economic Terrorism 


16 

While cyanide is primarily a compound used in various industrial applications, the 

compound has a long history of use as a weapon. This section discusses some potential 

and historical misuses of cyanide. Of current concern, someone gaining access to an air 

intake handler of a building can easily put cyanide gas into the forced air ventilation 

system. 





Slide 17 



Cyanide: Battlefield 

• WMD 

– Researched as a weapon in 

WW I 

– Used in concentration camps 

in WW II and in caves 

(Adjimushkaiskye) 

• Zyklon B 


17 





Slide 18 



Cyanide: Mass Murder 

Nazi Death Camps 

• Millions of Jews, gypsies, and 

others died 

in CN gas chambers 

• Gas chambers disguised as 

communal showers 

• Some suffering more than 

20 min before death 


18 

Cyanide is an extremely toxic and rapidly acting poison. During WWI and WWII, cyanide 

gas was employed as a chemical warfare agent; and, under the name Zyklon B, it was 

used as part of Hitler’s “Final Solution”. 

Zyklon B was the trade name of a cyanide-based insecticide infamous for its use by Nazi 

Germany against Jews and other minorities in the gas chambers of extermination (such 

as Auschwitz-Birkenau) camps during the Holocaust. This genocide resulted in the 

deaths of over 6 million people before the end of WWII. Death camp gas chambers were 

frequently disguised as communal showers. 





Slide 19 



Execution by Cyanide Gas Chamber 

• CN salts dropped into sulfuric 

acid HCN 

• Few states now use it 

• 1930 to 1980 (11 states): 

– 945 men 

– 7 women 

• 1960 Caryl Chessman told 

reporters he would nod his head 

if it hurt. He nodded his head for 

several minutes before he died. 


19 

Execution by cyanide gas chamber, now seldom used in the United States, continues to 

be practiced to this day. Typically, the gas used in US execution chambers is produced 

by dropping a sachet of cyanide salts into a vat of sulfuric acid. 

Increasing recognition of the gas chamber as a needlessly cruel and painful means of 

execution has lead many states to ban its use or provide inmates with more humane 

options (e.g., lethal injection). Ironically, even lethal injection has been criticized as being 

inhumane. Three states, Arizona, Maryland, and Missouri, retain the gas chamber as a 

secondary method of execution for inmates sentenced to death or having committed 

capital crimes before certain dates, though they have lethal injection as the primary 

method 





Slide 20 



Cyanide: Other Sources 

The most common source of 

cyanide exposure is 

incomplete combustion of: 

– Wood 

– Plastic 

– Rubber 

– Polyurethane 

– Wool 

– Silk 


20 

While numerous and dramatic cases of deliberate or accidental release of cyanide 

provide an important foundation for terrorism planning, the most common source of 

cyanide exposure is the incomplete combustion of construction materials and textiles 

(wood, plastic, rubber, polyurethane, wool, silk). Responders should be on the lookout 

for cases of cyanide poisoning among victims of fire and smoke inhalation. 





Slide 21 



Cyanide: Incomplete Combustion 

Happy Land Social Club Fire Bronx 1990: 87 deaths 


21 

The Happy Land Social Club fire was an arson fire which killed 87 people trapped in an 

unlicensed social club called "Happy Land" in the Bronx, New York City, on March 25, 

1990. Most of the victims were ethnic Hondurans celebrating Carnival. Unemployed 

Cuban refugee Julio González was arrested shortly after and ultimately convicted of 

arson and murder. 





Slide 22 



Cyanide: Incomplete Combustion 

The Station Nightclub Fire Providence 2003: 100 deaths 


22 

The Station nightclub fire occurred in West Warwick, Rhode Island on the evening of 

February 20th, 2003. This event, the fourth-deadliest nightclub fire in U.S. history, killed 

100 people and injured more than 200 others. Ninety-six perished on the night of the fire, 

and four died later from their injuries at local hospitals. Many died without burns or 

significant smoke inhalation, suggestive of a role for cyanide in causing or contributing to 

some of the deaths. 





Slide 23 



Cyanide: Homicide 


23 

Given its reputation and availability via the Internet, cyanide is a common weapon of 

choice for many would-be poisoners. In the story described on this slide, an 18 year old 

Maryland teen purchased 2 grams of potassium cyanide on the internet using his 

mother’s credit card. He poisoned and killed his best friend because of rivalry over a 

former girlfriend. The compound was administered by lacing his friend’s beverage while 

the two were playing video games. 





Slide 24 



Cyanide: Homicide 

Timeline: 

• 17 yr old male drinks KCN spiked soda 

• Feels unwell and goes to the bathroom 

• Emerges from the bathroom and collapses 

• EMS intubate for apnea. Vital signs present. 

• Cardiac arrest in hospital. ACLS and recovery. 

• Transfer to tertiary care center. 

• Dx made. Steps 2 & 3 of antidote kit administered. 

• No neurologic recovery. 


24 

This slide provides a timeline of events for the case study described on the previous 

slide. An indeterminate period after ingesting the cyanide spiked soda provided by his 

friend, the subject reported feeling unwell. Upon emerging from the bathroom the subject 

collapsed and emergency services were called. EMS responders intubated the subject 

due to the appearance of apnea (respiratory arrest) and determined that vital signs were 

present. While cyanide poisoning was not yet suspected, the patient was hospitalized 

and underwent standard testing. While in the Radiology suite for a CT scan, the subject 

went into cardiac arrest necessitating ACLS (Advanced Cardiac Life Support). The 

subject recovered and was subsequently transferred to a tertiary care center. A 

diagnosis of cyanide poisoning was reached and antidote steps 2 and 3 were 

administered. No neurologic recovery was noted. The victim went into respiratory arrest 

and died soon after. 

The antidote kit has 3 parts. Part 2 is sodium nitrite, given IV, and part 3 is sodium 

thiosulfate, also given IV. Part 1, not used in this case, is amyl nitrite, given by inhalation. 

Details about treatment for cyanide poisoning will be covered in subsequent slides. 





Slide 25 



Cyanide: Suicide 

• 55 yr old male ingests KCN tablets at sentencing 

hearing. 

• Subject tells lawyer who tells judge 

• In minutes: lethargy > collapse > shock 

• No antidote kit at scene 

• Subject received antidote kit at hospital 

(~15 min post -ingestion) 

• No neurological recovery. 


25 

Given its reputation, cyanide is also a common choice among people wishing to poison 

themselves. In the case described above, a 55 year old man consumed cyanide tablets 

during his sentencing hearing. The defendant informed his lawyer who in turn reported to 

the judge what he had done. A few minutes after the situation became known the 

individual became lethargic, went into shock, and collapsed. Though he received an 

antidote kit approximately 15 minutes after ingestion, no neurological recovery occurred 

and the patient subsequently died. 





Slide 26 



Cyanide: Mass Murder 

The Jonestown Massacre 

– Jonestown, Guyana (1978) 

– CN-laced Kool -Aid 

– 913 Deaths 


Jim Jones, a cult leader from the San Francisco area, established a commune for his 

followers in Jonestown, Guyana. In 1978, Jones, fearing extradition to the US for a 

variety of crimes, exhorted his disciples to drink Kool-Aid laced with potassium cyanide 

as part of a mass-murder/suicide pact. Over 900 men, women, and children were killed. 

While most succumbed to the effect of potassium cyanide, autopsy reports noted that 

many victims died of gunshot wounds or poisoning by other substances. 

26 





Slide 27 



Cyanide: Drug Tampering 

• Pharmaceutical Terrorism 

– 1982 – Acetaminophen 

– 1991 – Pseudoephedrine 


27 

In 1982, Tylenol capsules adulterated with cyanide were implicated in the deaths of 7 

Chicago-area residents. While the original perpetrator was never apprehended, this 

crisis lead to a federal mandate (“The Tylenol Bill”) for more stringent anti-tampering 

safeguards and closer oversight of the US drug supply. Since that time there have been 

several similar “copy-cat” cases of drug tampering. While the risk of exposure has been 

greatly reduced, the surreptitious introduction of cyanide (and other toxins) into 

pharmaceuticals remains a serious source of concern. 





Slide 28 



Cyanide: Terrorism 

Appearance at incidents: 

• NY WTC (1993) 

– Ingredients for HCN in the 

truck 

• Tokyo Subway (1995) 

– Sarin 

– Ingredients for HCN in 

bathroom 


28 

While neither of the two terrorist events (1993 World Trade Center bombing and the 

1995 Tokyo Sarin release) primarily involved cyanide, in both circumstances, the 

perpetrators appeared to be prepared to do so. This suggests that while radical groups 

may have more lethal means at their disposal, cyanide, by virtue of its availability and 

ubiquity, may provide a fall-back alternative and a supplemental means of attack. 

The 1993 World Trade Center bombing occurred on February 26, 1993, when a car 

bomb was detonated below Tower One of the World Trade Center in New York City. The 

1,500 lb (680 kg) urea nitrate-hydrogen gas enhanced device was intended to knock the 

North Tower (Tower One) into the South Tower (Tower Two), bringing both towers down 

and killing thousands of people. It failed to do so, but did kill six people and injured 

1,042. Ramzi Yousef and a Jordanian friend, Eyad Ismoil, drove a yellow Ryder van into 

Lower Manhattan, and pulled into the public parking garage beneath the World Trade 

Center around noon. There remains a popular belief that there was cyanide in the bomb, 

which is reinforced by Judge Duffy's statement at sentencing, "[y]ou had sodium cyanide 

around, and I’m sure it was in the bomb." However, the bomb's true composition was not 

able to be ascertained from the crime scene and Robert Blitzer, a senior FBI official who 

worked on the case, stated that there was "no forensic evidence indicating the presence 

of sodium cyanide at the bomb site." Furthermore, Yousef is said only to have 

considered adding cyanide to the bomb, and to have regretted not doing so in Peter 

Lance's book 1000 Years For Revenge. 

The Sarin (nerve agent) attack on the Tokyo subway was an act of domestic terrorism 

perpetrated by members of Aum Shinrikyo on March 20, 1995. In five coordinated 

attacks, the perpetrators released sarin on several lines of the Tokyo Metro, killing at 

least a dozen people, severely injuring fifty and causing temporary vision problems for 

nearly a thousand others. The bottom image shows the clean up crew on the subway car 

in Japan. 





Slide 29 



Cyanide: Environmental Terrorism 

• Cyanide spill into Tisza River, Romania (2000) 

• 100,000 cubic meters of cyanide containing water released 

when a gold mine dam overflowed 

• All river life killed for miles downriver 


29 

One of cyanide’s main industrial uses is in the processing of ore during the metal refining 

process. Accidental or deliberate release of the large amounts of cyanide used in the 

mining industry has the potential to cause serious and widespread environmental and 

economic damage. 

Several environmental disasters have occurred in Europe and South American when the 

tailing ponds where cyanide waste water is kept breach the banks. 





Slide 30 

Claims in 1989 that imported Chilean grapes contained cyanide resulted in a massive 

downturn in the Chilean fruit industry and caused irreparable harm to that nation’s 

economy. Based on phone calls placed to US, Canadian, and Japanese embassies 

threatening to poison Chilean fruit exports and the discovery of two cyanide-laden 

grapes, FDA officials seized all the country’s fruit exports and recommended that 

consumers destroy any fruit they had at home. While subsequent testing and 

investigation proved the risk to be minimal and the threat a likely hoax, the event had an 

undeniable impact on the Chilean economy ($333 million USD lost) and consumer 

purchasing habits. 





Slide 31 



Cyanide: Missing Cyanide (2004) 

• 15-gallon drum of sodium cyanide 

was lost from a delivery truck 

• Located after 1 -week search in N. 

Dakota 

– Was being hauled for delivery to 

beekeepers 

– Used to fumigate and kill excess 

bees 

– Not legally registered for this use 

• Became a multi -state 

investigation 


31 

In 2004 in North Dakota a 15 gallon drum of cyanide was “lost” from a delivery truck, and 

was found almost 2 weeks later. It was being transported to be used in beekeeping, 

which is not a registered use of cyanide. Obviously this was a concern to DHS and FBI 

given the possible use of this chemical against a population, and it became a multistate 

investigation. But this really demostrates just how easy it is to get, and to lose, cyanide. 

The case first came to light on Sept. 30, 2004, when passing motorists found two drums 

of sodium cyanide along ND Highway 1, north of Lakota, North Dakota. A trucker 

admitted that three barrels had fallen off his vehicle, and a search was launched to find 

the missing barrel. The missing barrel was found October 12 th , in a water-filled ditch 

along Highway 1 near Brocket, ND. The case initially drew the attention of the U.S. 

Department of Homeland Security and the FBI. After it was learned that the chemical 

was intended for beekeeping, it became an agricultural regulatory matter and NDDA 

took the lead role. Since the incident was first reported, NDDA investigators determined 

that 54 containers of sodium cyanide had been sold in North Dakota over the past two 

years. All have been traced to the same offender: EnviroKem. Eleven locations in North 

Dakota and six locations in other states were involved. Sodium cyanide is legally used in 

extracting precious metals, case-hardening steel and electroplating. It has no registered 

agricultural use. 





Slide 32 



Prehospital Care 

Cyanide: Treatment 

• Safely remove victims from source 

• Restore or maintain airway patency 

• Maximize oxygenation 

– 100% NRBM or BVM 

• Cardiopulmonary support to maintain VS 

– IVF and/or dopamine, norepinephrine 

• Decontamination 


32 

Given all these potential sources and nefarious uses of cyanide, let’s look at some 

treatment issues. In any setting with multiple people incapacitated or “found down”, one 

should always consider the surroundings potentially hazardous. 

After removal from the scene (with appropriate attention to rescuer safety), the treatment 

of cyanide poisoning starts with oxygenation and supportive care. 

Intubation and manual ventilation are often required to provide an airway and 

oxygenation. Specific antidotes exist and need to be given as soon as possible after 

exposure in order to save lives. Currently two different antidote kits are available in the 

US: the traditional 3-step (“Eli Lilly” or Taylor) kit or the more recently approved one-step 

Cyanokit® (Merck). We will discuss these in the next few slides. 

Once the patient has been stabilized decontamination procedures may be initiated, if 

indicated (more appropriate for ingested cyanogenic compounds or dermal contact with 

powder or liquid). 





Slide 33 



Cyanide Antidote Kit (CAK) 

• 3-steps 

– Amyl nitrite 

– Sodium nitrite 

– Sodium thiosulfate 

• Converts cyanide to 

thiocyanate 

• One kit treats two people 


33 

The first and oldest antidote is the 3-step cyanide antidote kit, still referred to as the “Lilly 

kit”. The first step involves the inhalation of amyl nitrite in the nares of the victim to 

induce a methemoglobinemia. Step two involves intravenous administration of sodium 

nitrite another methemoglobin inducer. Methemoglobin can bind cyanide to form 

cyanomethemoglobin. The third and last step involves the intravenous administration of 

sodium thiosulfate which binds the cyanide from methemoglobin forming thiocyanate, a 

renally excretable substrate. Sodium thiosulfate has a somewhat delayed onset of 

action, which is why the methemoglobin inducers are used. One kit treats two adults, or 

one adult twice, but full prescribing information is written on the box inside cover. 





Slide 34 



Cyanide: CAK 

CAK Dosing 

• Amyl nitrite - inhale if no IV access yet 

• Sodium nitrite (3% solution) 

– Adults 300 mg (10 ml) IV over 15-20 min 

– Peds Hgb based 

• Sodium thiosulfate (50 ml 25% solution) 

– Adults 12.5 g (50 ml) IV 

– Peds 1.65 ml/kg IV 

• May repeat if large cyanide exposure 


34 

Amyl nitrite is best used in the pre-hospital setting and should be administered by 

inhalation only. The application of amyl nitrite induces methemoglobinemia which begins 

the process of binding free cyanide. This process is continued in the hospital setting by 

the application of sodium nitrite in 3% solution. Adults should receive 300mg (10ml) IV 

infusion over the course of 15-20 minutes, while pediatric dosing should be determined 

based on hemoglobin values. The process of eliminating the bound cyanide is started by 

the application of sodium thiosulfate in 25% solution. Adults should receive 12.5g (50 ml) 

IV while pediatric dosing be 1.65 ml/kg IV. Thiosulfate converts cyanohemoglobin to 

thiocyanate which can then be renally excreted. 





Slide 35 



• Effective 

• Safe 

• Side Effects 

– Nitrite 

• Hypotension 

• MetHb 

– Sodium Thiosulfate 

• vomiting 

Cyanide: CAK 


35 

While generally safe and effective several undesirable adverse effects are associated 

with CAK therapy. The administration of nitrite may induce hypotension and 

methemoglobinemia, while sodium thiosulfate may induce vomiting. 

. 





Slide 36 



Cyanokit 

• Hydroxocobalamin 

• Converts cyanide to 

cyanocobalamin 

(vitamin B12) 

Cyanide: Cyanokit 

Dosing 

• 5g IV 

• 10g IV in cardiac arrest 


36 

The newer antidote is the one-step “Cyanokit®” which contains hydroxocobalamin. This 

antidote has been in use in Europe for decades and was introduced in the US in 2006. 

Hydroxocobalamin is administered intravenously and binds with cyanide to form 

cyanocobalamin (i.e. vitamin B12) which is renally excretable. The dose is 5 grams 

intravenously if the patient is symptomatic and 10 grams if the patient is suffering from 

cardiac arrest. 





Slide 37 

Compared to the CAK, hydroxocobalamin has a fast onset of action and is associated 

with minor adverse effects such as red discoloration of skin and urine. Because of its 

intense color, it can interfere with cooximeter readings. Hydroxocobalamin was given an 

expedited review and was approved for use in the treatment of cyanide poisoning in 

December 2006. Its main advantage is its ease of use and the lack of methemoglobin 

formation (which would be problematic in the setting of concomitant carbon monoxide 

poisoning) 





Slide 38 



Cyanide as a Weapon 

An Ideal Terrorist Weapon 

• Plentiful 

• Readily available 

• Special knowledge not required 

• Capable of causing mass casualties 

• Capable of causing social disruption 

• Requires large quantities of resources to combat its 

effects 


38 

Since cyanide is easy to obtain, plentiful, and easily converted into gaseous form, it is 

capable of causing mass casualties and social disruption. It requires large quantities of 

resources to control its effects (rapid response, ventilation, and specific antidotes, which 

may not be readily available). Thus, it is ideally suited for use as a weapon. 





Slide 39 



Any terrorist attack that involves explosions or fire 

will likely result in HCN release 


39 

Any event which produces fire will invariably generate cyanide as a combustion byproduct. 





Slide 40 



Fumigant Gases 

• Sulfuryl fluoride ( Vikane 7) 

• Methyl bromide 

• Phosphine 


40 

The three most common fumigants regulated by the US Department of Environmental 

Protection and the Department of Agriculture are sulfuryl fluoride (Vikane 7), methyl 

bromide, and phosphine. Although fumigants are very toxic and their distribution 

regulated, they remain surprisingly easy to obtain. While not generally available through 

retail locations or Internet ordering sites, these agents can be purchased directly from 

chemical supply companies. 

Fumigation is a method of pest control that completely fills an area with gaseous 

pesticides to suffocate or poison the pests within. It is utilized for control of pests in 

buildings (structural fumigation), soil, grain, and produce, and is also used during 

processing of goods to be imported or exported to prevent transfer of exotic organisms. 





Slide 41 



Fumigants 

Applications 

• Insect or rodent control in grain storage 

• Insect or rodent control in structures 

• Eradication of soil pests in farming 


41 

Fumigants are agents used in the home and numerous agricultural and industrial 

industries for the extermination and control of a variety of pests (termites, fungi, 

nematodes, etc.). A substantial number of exposures to fumigants reported to Poison 

Centers are due to the fact that civilians reenter a dwelling before it is safe to do so. A 

substantial number of exposures to fumigants reported to Poison Centers are due to the 

fact that civilians reenter a dwelling before it is safe to do so. 

Structural fumigating techniques differ from building to building, but in houses a rubber 

tent is often placed over the entire house while the pesticides are being released into the 

residence. This concentrates the gases and prevents them from escaping and doing 

harm to people in the neighborhood. During this time the residents of the house must 

find an alternate residence for up to a week depending on the fumigant used, which in 

turn depend on the severity of infestation and size of the house. 

The picture on the left is of a grain storage silo on a farm (potential site for phosphine 

use) 

The middle photograph shows a house that has been completely tented in preparation 

for injection of a fumigant (typically sulfuryl fluoride with a tearing agent, such as 

chloropicrin) 

The photograph on the right shows a pressurized cylinder and injection apparatus for 

soil application in farming (previously usually using methyl bromide). 





Slide 42 



Fumigant Gases 

• Like HCN, could be introduced into a closed space 

through ventilation system or other conduits 


42 

In 2003, the US Department of Homeland Security (DHS) issued a bulletin warning of 

the possibility of terrorists using ventilation systems to disperse cyanide gas. Although 

not part of the bulletin, fumigants could be similarly deployed. 





Slide 43 



• Used in 85% of building 

fumigations 

• Colorless 

• Odorless 

• Irritating 

• 3.5 times heavier than air 

• Exposure to fatal 

concentrations possible 

without warning odor 

• No re-entry until air levels < 

5 ppm 

Sulfuryl Fluoride 

O 

F 

S 

O 

F 


43 

Popular for over 50 years in the extermination industry, sulfuryl fluoride is the most 

frequently used fumigant in the United States. It is usually obtained in canisters and 

sprayed into vacant buildings for the purposes of pest-control. Because of its lack of 

color and odor, it is often admixed at the scene with a small amount of chloropicrin (a 

potent lachrymator) to enhance detection. 





Slide 44 



• Clinical Manifestations 

– High concentrations 

• Seizures 

• Syncope / dysrhythmias 

• Respiratory arrest 

– Lower concentrations: 

• Vomiting 

• Diarrhea 

• Salivation 

• Lung injury 



44 

Clinical signs of sulfuryl fluoride exposure are concentration dependent and may include 

vomiting, diarrhea, salivation, and lung injury at lower concentrations and, in higher 

doses, may lead to seizures, syncope/dysrhythmias, and respiratory arrest. 

Acute and delayed symptoms of poisoning may also include depression, slowed gait, 

slurred speech, stomach pain, drunkenness, itching, numbness, twitching, and seizures. 

Skin contact with sulfuryl fluoride normally poses no hazard, but contact with liquid 

sulfuryl fluoride can cause pain and frostbite due to rapid vaporization. 

Sulfuryl fluoride gas is odorless and colorless, does not cause tears or immediately 

noticeable eye irritation, and lacks any other warning property. Thus, chloropicrin is 

added. 

. 





Slide 45 



Management 

Sulfuryl Fluoride: Treatment 

• Removal from source of exposure 

• Ventilation 

• Oxygen 

• Monitor for hypocalcemia 

– ECG (prolonged QTc) 

– Serum or ionized Ca2+ 

• Administer calcium as needed 


45 

As with all fumigants and gases the first step is to remove the patient from the exposure 

source. Treatment should include ventilation and oxygen and the patient should be 

monitored for hypocalcemia (usually identified on the ECG as a prolonged QT interval or 

by obtaining a Serum or ionized Ca 2+ measurement). 

Intravenous calcium is the treatment for this complication. 

There is no specific antidote for sulfuryl fluoride itself. 

The fluoride ion may be released from the compound in the body. This fluoride can bind 

blood calcium and cause hypocalcemia, which results in neurologic and cardiac 

abnormalities, which can be fatal if not treated. If patients develop fluoride-induced 

hypocalcemia, the treatment is large doses of intravenous calcium chloride or calcium 

gluconate. 

Depending on the background of the participants, many will not be familiar with 

electrocardiograms (ECG) monitoring or the specific intervals, such as the period of 

cardiac electrical repolarization, as represented by the QT interval. A simple notation 

that this interval is prolonged by many factors, including a very low blood calcium, is 

sufficient. 





Slide 46 




Elderly couple reenter fumigated home before Vikane 

had fallen to a safe levels: 

• Husband: 

– Shortness of breath, seizures 

– Death 48 hrs after reentry 

• Wife: 

– Weakness, nausea, vomiting 

– Death 72 hrs after reentry (lung damage) 


46 

This case study demonstrates the typical presentation in cases of sulfuryl fluoride 

poisoning. An elderly couple reentered their recently fumigated home before the 

concentration of Vikane had fallen to a safe level. The husband experienced shortness 

of breath, developed seizures, and died 48 hours later. The wife experienced weakness, 

nausea, and vomiting. She died 3 days later from lung damage. 





Slide 47 



Methyl Bromide 

• Odorless, colorless gas 

• Chloropicrin (lachrymator) added as 

warning agent 

• MeBr heavier than air 

• Broad spectrum of activity 

– Alkylating agent 

• Penetrates rubber and neoprene 

• Being phased out due to environmental 

concerns 


Br 

CH 3 

47 

Methyl bromide, another fumigant gas, is less commonly used in the United States 

currently because of adverse effects on the environment (ozone depletion). However, it 

remains popular in many foreign countries. It is both colorless and odorless. Because of 

its lack of color and odor, (like sulfuryl fluoride) it is often pre-prepared and shipped with 

chloropicrin (a potent lachrymator) to enhance its detection. 

Methyl bromide, sometimes called bromomethane, is an organic halogen compound with 

formula CH 3 Br. It is a colorless, nonflammable gas with no distinctive smell. Its chemical 

properties are quite similar to those of chloromethane. It is a recognized ozone-depleting 

chemical. It was used extensively as a pesticide until being phased out by most 

countries in the early 2000s per the Montreal Protocol. 





Slide 48 



Methyl Bromide: Clinical Signs 

• Acute high -level exposure rapid onset of sxs 

– CNS depression, delirium, seizures, pulmonary edema 

– Skin injury, burns, blistering reported with high -level dermal exposure 

• Lower level exposure 

– Delayed onset toxicity well -documented 

– Mucosal irritation 

– Headache, dizziness, Nausea, vomiting 

– Progression (hours) to visual symptoms, ataxia, tremor, delirium , 

seizures 

• Sxs reversible with mild intoxication 

– Permanent effects have been reported in severe cases 


48 

Acute high level exposure results in the rapid onset of clinical symptoms. These include 

coma and irritant injury of the skin and airways. Lower level acute exposures results in 

less severe effects, with a slightly delayed onset of several hours. Many of the effects, 

particularly those involving the central nervous system, are not reversible. 

The liquid burns the skin, producing itching and reddening, then blisters several hours 

after contact. Both liquid and vapour severely damage the eyes. 





Slide 49 



Methyl Bromide: Case Study 

• Adult female occupying a guest house rapidly developed 

headache, flu -like symptoms 

• Within 24 hours, found in status epilepticus 

• Initial labs remarkable for severe liver, kidney injury 

• Expired 19 days post -exposure 

• A building next door had undergone fumigation with methyl 

bromide. Seven 1 -2 inch underground conduits connected 

the buildings. 

• Methyl bromide had traveled from the adjacent building into 

the cottage. 


49 

This case report from the California Poison Center shows a typical course for high level 

methyl bromide exposure. An adult woman developed headache and severe 

neurological findings (seizure) and subsequently died after exposure to methyl bromide 

used to fumigate a nearby house. 

It was not known at the time that the two houses were connected by an undergound 

conduit, which allowed the methyl bromide to enter the victims home. 





Slide 50 



Phosphine (PH 3 ) 

• Forms 

– Gas (vapor density 1.17) 

– Aluminum and Zinc phosphide 

pellets 

• Smells like garlic and rotten fish 

• Many uses in agriculture & structural 

pest control 

• Used in semiconductor industry 

• Concentration effects 

– 400-600 ppm - severe toxicity in 

30 min 

– 1000 ppm - immediate death 


50 

Phosphides, typically distributed in pellet form, are commonly used in agricultural 

settings for the fumigation of grain and widely used in the semiconductor industry. In 

gaseous form phosphine is heavier than air and produces severe toxic effects above 400 

ppm. Exposures exceeding 1000ppm usually lead to immediate death. 

Phosphine is the common name for phosphorus hydride (PH3). It is a colorless, 

flammable gas with a boiling point of -88 °C at standard pressure. Pure phosphine is 

odorless, but technical grade phosphine has a highly unpleasant odor like garlic or 

rotting fish, due to the presence of substituted phosphine and diphosphine (P2H4). 





Slide 51 



Generating Phosphine Gas 


51 

Phosphides break down (on contact with water, oxygen, acid) to yield phosphine gas, 

the active pesticidal agent. 

Phosphine should not be confused with phosgene which is discussed in the Toxic Gases 

module. 

Aluminum phosphide is used as a rodenticide, insecticide and fumigant for stored cereal 

grains. It is used to kill small verminous mammals such as moles, rabbits, and rodents. 

Once wet, either in the environment or the GI tract of a rodent, phosphine is liberated. In 

some parts of the world, aluminum or zinc phosphide ingestion is a leading cause of 

suicide by overdose. 





Slide 52 



Clinical 

Phosphine : Treatment 

• Early/mild cases 

– Non-specific 

– GI effect, cough, chest tightness, eye irritation 

• Late/serious exposure 

– Pulmonary edema, coma, seizures, death 

– Knock-down gas 

• Rapid progression and deterioration in fatal cases 


52 

Shortly after exposure or following very low-dose exposure, patients will present with 

non-specific symptoms that may include GI effects (nausea, vomiting), cough, tightness 

of the chest, and eye irritation. If treatment is delayed or the exposure is heavier, 

subjects may experience pulmonary edema, coma, and seizure leading to death. 

Typically symptoms progress rapidly in cases of fatal exposure. 





Slide 53 



Phosphine: Case Study 

• 5-year-old girl suddenly develops difficulty breathing at home 

• Has a cardiac arrest - Unable to resuscitate 

• Family members were ill as well 

– Developed acutely after a period of heavy rainfall 

– Odor noted in basement 

• Investigation: a cupful of aluminum phosphide pellets had 

been placed in a hole adjacent to the basement foundation 

• Child’s father was a professional exterminator 


53 

As indicated by this case study, mishandling and misuse are the most common causes 

of phosphine exposure. In this case a young girl developed difficulty breathing and 

suffered a cardiac arrest, and several other family members were ill. The investigation 

identified aluminum phosphide pellets, which had been placed by the father (an 

exterminator) in a potential site of rodent entry in the basement had become wet, and 

likely released the phosphine gas. 





Slide 54 

The illicit synthesis of methamphetamine also produces phosphine and has resulted in 

toxic exposures for both the “cooks” and first responders. The Willers paper describes 

three dead victims in a hotel room where methamphetamine was being synthesized. The 

Burgess paper detailed a law enforcement agent who was exposed to phosphine during 

a methamphetamine raid. He developed chronic lung disease following this initial 

exposure. 





Slide 55 



Treating Fumigant Poisoning 

• No antidotes available 

• Remove victim from source 

• Thorough decontamination 

• Oxygenation 

• Symptomatic and supportive care as indicated 


55 

All exposures to fumigants should be treated with immediate removal from source, 

thorough skin and eye decontamination, oxygenation, supplemented by symptomatic 

and supportive care. No specific antidote is available for any of these exposures. 

Treatment of hypocalcemia sometimes seen with sulfuryl fluoride poisoning may be 

necessary. 

Supportive care is indicated. This includes oxygen and decontamination of exposed skin 

and eyes. A full “wet decon” is not usually necessary for a vapor or gas exposure alone. 





Slide 56 



Fumigants: Summary 

Gas 

Vikane 

Methyl 

Bromide 

Properties 

Poorly 

detectable 

(occasionally 

mixed with 

chloropicrin) 

Poorly 

detectable 

(occasionally 

mixed with 

chloropicrin) 

Clinical manifestations 

Neurologic 

Gastrointestinal 

Potentially delayed onset 

Mucous membranes irritation 

Neurologic 

Seizures 

Lung 

Management 

Remove from 

exposure 

Flush skin/eyes 

100% O2 

Supportive care 

Same 

Phosphine 

Fishy / garlic 

odor 

Neurologic, Cardiac, Lung 

Same 


56 

This chart is a reminder and comparison of the different fumigants that we have 

discussed today. It shows some of the sensory warning properties (or lack thereof), the 

clinical signs of poisoning, and management strategies, which are essentially supportive. 





Slide 57 




Which of the following is added to fumigants to 

make them more easily detectable 

1. Mercaptans 

2. Hydrogen sulfide 

3. Chloropicrin 

4. Organophosphates 

5. Yellow dye number 20 


57 





Slide 58 



Summary 

• Forced air ventilation systems could be used by terrorists to 

disperse toxic gases or aerosols. 

• Cyanide gas and fumigants are easily obtained and well - 

suited for airborne dispersal. 

• Cyanide gas exposure should be treated with oxygenation, 

supportive care, and antidotal therapy. 

• No antidote is available for the fumigants discussed in this 

module. Treatment should focus on decontamination and 

supportive therapy. 


58 

Cyanide and fumigants constitute a threat to the general population because they are 

widely available, easily weaponized, and can be highly toxic if inhaled. In a 2003 bulletin, 

the US Department of Homeland Security warned of the possible use of cyanide gas as 

a weapon and the threat of its introduction into forced air ventilation systems. Fumigants, 

while more tightly controlled, could easily be used in a similar fashion. 





Slide 59 

Any Questions 





Module Four Summary 

Cyanide and fumigants constitute a threat to the general population because they are widely 

available, easily weaponized, and can be highly toxic if inhaled. In a 2003 bulletin, the US 

Department of Homeland Security warned of the possible use of cyanide gas as a weapon and 

the threat of its introduction into forced air ventilation systems. Fumigants, while more tightly 

controlled, could easily be used in a similar fashion. 

Cyanide is an extremely toxic and rapidly acting poison. Discovered in 1782 by the noted 

Swedish chemist Carl Wilhelm Scheele [1742 – 1786], prussic acid (hydrogen cyanide) was 

found to have numerous industrial applications. During WWI and II, cyanide gas was employed 

as a chemical warfare agent and, under the name Zyklon B, used as part of Hitler’s “Final 

Solution”. Popular conceptions of cyanide have been shaped by its frequent appearance as a 

murder weapon in detective fiction and by tragic real-world mass poisonings. 

Given its abundant legitimate uses, cyanide can be easily purchased in a variety of forms – 

most commonly sodium cyanide, potassium cyanide, and calcium cyanide. Using a simple 

chemical reaction, cyanide salts can be mixed with an acid to produce hydrogen cyanide gas. 

The dose of cyanide required to produce toxicity varies with type of exposure. About 200 mg of 

potassium cyanide is lethal if ingested, whereas airborne concentrations of >110ppm for 30 

minutes are generally considered fatal. 

Cyanide acts by inhibiting specific enzymes – predominantly cytochrome aa3 in the 

mitochondrial electron transport chain – resulting in the complete arrest of cellular respiration 

and chemical asphyxiation of cells. The heart and CNS system, being the most oxygensensitive 

organs in the human body, are most affected by cyanide poisoning. Cyanide may also 

impact myocardial cells but this effect is, as yet, not well established. 

The clinical effects of cyanide poisoning include: gasping, syncope, and cardiac arrest. There is 

no specific constellation of signs and symptoms; no toxidrome. The oft-discussed bitter almond 

scent is not a reliable indicator of the presence of cyanide gas. Cyanide poisoning should be 

suspected whenever a group of people seem to have collapsed following an unknown inhalation 

exposure. 

The clinical laboratory can be useful in making the diagnosis of cyanide poisoning. Anion gap 

metabolic acidosis is usually present and it is due to the presence of large amounts of lactate 

(L-lactate). Arteriolization (i.e., inability of peripheral tissues to use oxygen) of the venous blood 

gas may be present. This leads to a very poor oxygen extraction ratio and a very high content of 

oxyhemoglobin in the venous blood. Oxygen saturations of >80% in venous blood are highly 

suggestive of arteriolization phenomenon. Blood cyanide levels can also be obtained but these 

are usually performed outside the hospital setting and have a 2-3 day turnaround time. 

The treatment of cyanide poisoning starts with oxygenation and supportive care. Intubation and 

ventilation are often required. Specific antidotal therapies exist and need to be applied as soon 

as possible after exposure. Currently two different antidote kits are available in the US: the 

traditional 3-step (“Eli Lilly”) kit or the more recently approved one-step Cyanokit® (Merck). 

The first and oldest antidote is the 3-step cyanide antidote kit, still affectionately still referred to 

as the Eli Lilly kit. The first step involves the insufflation of amyl nitrite capsules in the nares of 

the victim to induce a methemoglobinemia. Step two involves intravenous administration of 

sodium nitrite another methemoglobin inducer. Methemoglobin can bind cyanide to form 

cyanomethemoglobin. The third and last step involves the intravenous administration of sodium 





thiosulfate which binds the cyanide from methemoglobin forming thiocyanate, a renally 

excretable substrate. Sodium thiosulfate has a delayed onset of action, which is why the 

methemoglobin inducers are used. The adverse effects associated with the administration of 

both forms of nitrites include hypotension and methemoglobin formation. 

The newer antidote is the one-step “Cyanokit®” which contains hydroxocobalamin. This 

antidote has been in use in Europe for decades and was introduced in the US in 2006. 

Hydroxocobalamin is administered intravenously and binds with cyanide to form 

cyanocobalamin (i.e. vitamin B12) which is renally excretable. The dose is 5 grams 

intravenously if the patient is symptomatic and 10 grams if the patient is suffering from cardiac 

arrest. It has a fast onset of action and is associated with minor adverse effects such as red 

discoloration of skin and urine. Because of its intense color, it can interfere with cooximeter 

readings. 

Fumigants are agents used in the home and numerous agricultural and industrial industries for 

the extermination and control of a variety of pests (termites, fungi, nematodes, etc.). The four 

most common fumigants regulated by the US Department of Agriculture are Vikane (sulfuryl 

fluoride), methyl bromide, phosphine, and chloropicrin. Although fumigants are very toxic and 

their distribution regulated, they remain surprisingly easy to obtain. While not generally 

available, through retail locations or Internet ordering sites, these agents can be purchased 

directly from chemical supply companies. 

Popular for over 50 years in the extermination industry, Vikane (sulfuryl fluoride) is the most 

frequently used fumigant in the United States. It is usually obtained in canisters and sprayed 

into vacant buildings for the purposes of pest-control. Monitors are used to determine when it is 

safe for occupants to return. Vikane has no warning properties as it is both colorless and 

odorless. Exposure produces respiratory symptoms, seizures, coma, and death. 

Methyl Bromide, being more toxic to humans, is less commonly used in the United States, 

however, it remains popular in many foreign countries. It is both colorless and odorless. The 

clinical effects can be delayed and may include: respiratory symptoms, seizures, and coma. 

Seizures from methyl bromide are specifically associated with poor outcomes. 

Phosphides, typically distributed in pellet form, are commonly used in agricultural settings for 

the fumigation of grain. Pellets are mixed with water or an acid to produce phosphine gas. 

Phosphine is colorless and has a fishy or sometimes garlicky odor. Clinical effects include 

lethargy, coma, and lung injury. 

All exposures to fumigants should be treated with immediate removal from source, thorough 

skin and eye decontamination, oxygenation, supplemented by symptomatic and supportive 

care. No specific antidote is available for any of these exposures. 





Module Five 

Chemical Contamination of Food, Water, & Medication - 


Safe food and water are among the basic necessities of life. Pharmaceuticals are widely used 

and generally considered safe in the United States. However, as past domestic and foreign 

crises have demonstrated, modern centralized production and distribution systems for these 

critical resources provide a tempting target to would-be terrorists. 

Duration 

45 minutes 


This module provides an overview of US food, drug, and water production systems with a view 

towards identifying potential threats and vulnerabilities. Past incidents are discussed and used 

to contextualize existing preventive measures and regulations. 


• Identify potential vulnerabilities in relation to the properties of selected 

chemical agents in our water, food, and drug supply systems. 


Resources 

• Describe how US drinking water is produced and protected 

• Identify system vulnerabilities and potential chemical agents of 

concern, using past incidents of water, food, and drug contamination 

or terrorism 

• Describe significant episodes of water, food, and medication 

contamination that have resulted in system-wide changes or 

legislation 

• Identify resources detailing measures used to protect the US water, 

food, and drug supplies 













1. An Introduction to Cross-Connection Control. Foundation for Cross- 

Connection Control and Hydraulic Research. University of California 

Viterbi School of Engineering, 2005. Accessed Dec 2008 from: 

http://www.usc.edu/dept/fccchr/intro.html 

2. Arnon SS, Schechter R, Inglesby TV. Botulinum toxin as a biological 

weapon: medical and public health management. JAMA. Feb 

28 2001;285(8):1059-70. 

3. Bell R. The Tylenol Terrorist. truTV, Turner Broadcasting System, Inc. 


http://www.trutv.com/library/crime/terrorists_spies/terrorsts/tylenol_mu 

rders/4.html 

4. Burrows WD and Renner SE. Biological warfare agents as threats to 

potable water. Environ Helath Perspect 1999;107(12):975-984. 

5. Centers for Disease Control and Prevention. Chlorine Residual 

Testing Fact Sheet, SWS Project. Accessed Dec 2008 from: 

http://www.cdc.gov/safewater/publications_pages/chlorineresidual.pdf 

6. Centers for Disease Control and Prevention. Fatalities Associated 

with Ingestion of Diethylene Glycol-Contaminated Glycerin Uesd to 

Manufacture Acetaminophen Syrup—Haiti, November 1995-June 

1996. MMWR 1996;45(30):649-650. 

7. Centers for Disease Control and Prevention. BioSense. Accessed 

Dec 2008 from: http://www.cdc.gov/BioSense/ 

8. Chertow DS, Tan ET, Maslanka SE, et al. Botulism in 4 adults 

following cosmetic injections with an unlicensed highly concentrated 

botulinum preparation. JAMA 2006;296(20):2476-9. 

9. Clark RM, Deininger RA. Protecting the nation’s critical infrastructure: 

the vulnerability of U.S. water supply system. J Contingencies Crisis 

Management 2000;8(2):73-80. 

10. Cockburn R, Newton PN, Agyarko EK, et al. The global threat of 

counterfeit drugs: why industry and governments must communicate 

the dangers. PLoS Med 2005;2(4):e100. 

medicine.plosjournals.org/archive/1549- 

1676/2/4/pdf/10.1371_journal.pmed.0020100-L.pdf 

11. Denileon GP. The Who, What, Why and How of Counterterrorism 

Issues. J Amer Water Works Assoc 2001;93(5):78-85. 

12. Diethylene Glycol. Health Council of the Netherlands; 2007. Accessed 

Dec 2008 from: www.gezondheidsraad.nl/pdf/phpID=1606&p=1 

13. Dunea G. Death over the counter. Br Med 1983;286(6360):21-212. 

14. Environmental Protection Agency. Drinking Water Treatment. 


http://www.epa.gov/ogwdw/sdwa/30th/factsheets/pdfs/fs_30ann_treat 

ment_web.pdf 





15. Environmental Protection Agency. Potential Contamination Due to 

Cross-connections and Backflow and Associated Health Risks. Issue 

Paper US EPA Office of Ground Water and Drinking Water 

(OGWDW); Aug 2002. 

16. Environmental Protection Agency. Response Protocol Toolbox: 

planning for and responding to drinking water contamination threats 

and incidents. Accessed Dec 2008 from: 

http://www.epa.gov/safewater/security. 

17. Environmental Protection Agency. Safe Drinking Water Act. Accessed 


http://www.epa.gov/OGWDW/sdwa/basicinformation.html 

18. Faircloth JM. Dechlorination Procedure using Sodium Thiosulfate. 

DEP/State of Florida. Accessed Dec 2008 from: 

ftp.dep.state.fl.us/pub/labs/lds/sops/4032.pdf 

19. Farre ML, Garcia M-J, Tirapu L et al. Wastewater toxicity screeing of 

non-ionic surfactants by Toxalert and Microtox bioluminescence 

inhibition assays. Analyt chim acta 2001;427(2):181-189. 

20. FDA Finds Hazardous Levels of Selenium in Samples of "Total Body 

Formula" and "Total Body Mega Formula“ - Dietary supplement 

products linked to adverse reactions. FDA Press Release. April 9, 

2008. Accessed Dec 2008 from: 

www.fda.gov/bbs/topics/news/2008/new01818.html 

21. Food and Drug Administration. Dietary Supplement Health and 

Education Act of 1994. FDA; Center for Food Safety and Applied 

Nutrition; 1995. Accessed Dec 2008 from: 

http://www.cfsan.fda.gov/~dms/dietsupp.html 

22. Food and Drug Administration. Food Safety: A Team Approach. 


http://www.cfsan.fda.gov/~lrd/foodteam.html 

23. Food and Drug Administration. Grade “A” Pasteurized Milk Ordinance 

(2005 Revision). Accessed Dec 2008 from: 

http://www.cfsan.fda.gov/~ear/pmo05-2.html 

24. Food and Drug Administration. Questions and answers on heparin 

sodium injection (Baxter). FDA Center for Drug Evaluation and 

Research. 2008. Accessed Dec 2008 from: 

http://www.fda.gov/cder/drug/infopage/heparin/heparinQA.htm 

25. Food and Drug Administration. Risk Assessment for Food Terrorism 

and Other Food Safety Concerns Accessed Dec 2008 from: 

http://www.cfsan.fda.gov/~dms/rabtact.html 

26. Food and Drug Administration. Standards For Grade “A” Pasteurized, 

Ultra-Pasteurized and Aseptically Processed Milk and Milk Products. 

Accessed Dec 2008 from: http://www.cfsan.fda.gov/~ear/pmo03- 

4.html 

27. Food and Drug Administration, Office of Regulatory Affairs: 

Compliance. Tamper-Resistant Packaging Requirements for Certain 





Over-the-Counter (OTC) Human Drug Products (CPG 71321.17). 


http://www.fda.gov/ora/compliance_ref/cpg/cpgdrg/cpg450-500.html 

28. Gelpi E, de la Paz MP, Terracini B, et al. The Spanish toxic oil 

syndrome 20 years after its onset: a multidisciplinary review of 

scientific knowledge. Environ Health Perspect 2002;110(5):457-464. 

29. Gerhardt A, Ingram MK, Kang IJ, Ulitzur S. In situ on-line toxicity 

biomonitoring in water: recent developments. Environ Toxicol Chem 

2006;25(9):2263-2271. 

30. Government Accounting Office (GAO). Federal Oversight of Food 

Safety: high-risk designation can bring attention to limitations in the 

government’s food recall programs. Accessed Dec 2008 from: 

http://www.gao.gov/new.items/d07785t.pdf 

31. Haas CN. Benefits of using a disinfectant residual. J Amer Water 

Works Assoc 1999;91(1):65-69. 

32. Kalluri P, Crowe C, Reller M, et al. An outbreak of foodborne botulism 

ssociated with food sold at a salvage store in Texas. Clin Inf Dis 

2003;37:1490-1495. http://cdc.gov/enterics/publications/429- 

Kalluri2003.pdf 

33. Kishimoto TK, Viswanathan K, Ganguly T, et al. Contaminated 

heparin associated with adverse clinical events and activation of the 

contact system. NEJM 2008;358(23)2457-2467. 

34. Ko RJ. Adulterants in Asian patent medicines. NEJM 1998;339:847. 

35. Krouse M. Backflow incident sparks improvements. Opflow 

2001:27(2):1,4-5,7,14. 

36. Lechelt M, Blohm W, Kirschneit B, et al. Monitoring of surface water 

by ultra-sensitive Daphnia Toximeter. Environ Toxicol (Symposium 

ISTA 9) 2000;15(5):390-400. 

37. Lerner I. “Gold Pushing Cyanide” in ISIS News, December 18 2006. 


http://www.icis.com/Articles/2006/12/15/2017988/gold-pushingcyanide.html 

38. McKay CA. Risk Assessment and Communication. in Flomembaum 

NE, Goldfrank LR, Hoffman RS, Howland MA, Lewin NA, Nelson LS 

(eds.) Goldfrank’s Toxicologic Emergencies. McGraw-Hill Publishers, 

NYC, 8th edition, 2006. 

39. Meinhardt PL. Physician Preparedness for Acts of Water Terrorism: 

Recognizing waterborne disease and the health effects of water 

pollution. www.waterhealthconnection.org. 

40. Morgenstern LB, Viscoli CM, Kernan WN, et al. Use of ephedracontaining 

products and risk for hemorrhagic stroke. Neurology 

2003;60(1):132-135. 

41. Morrison J, Mancl K. Water System Pressure Sources. In Manel K 

(ed.) Water systems for small communities. The Ohio State University 

Extension Bulletin 910;2003. 





42. National Research Council. Public Water Supply Distribution Systems: 

Assessing and Reducing Risks—First Report. National Academies 

Press, Washington D.C. 2005. 

43. Nickels G. Reservoir Covering Program. Seattle.gov. Accessed Dec 

2008 from: 

http://www.seattle.gov/util/About_SPU/Water_System/Projects/Reserv 

oir_Covering_Program/index.asp 

44. Notermans S and Havelaar AH. Removal and inactivation of 

botulinum toxins during production of drinking water from surface 

water. Antonie van Leeuwenhoek 1980;46(5):511-514. 

45. Quimby B. “Three years later, church still feeling effects of poisoning; 

Its pastor says the Gustaf Adolph church, which some members have 

left, needs more time to heal.” Portland Press Herald, April 20 2006. 

Accessed Dec 2008 from: http://www.encyclopedia.com/doc/1P1- 

122178383.html 

46. Scalzo AJ. Diethylene glycol toxicity revisited: the 1996 Haitian 

epidemic. J Toxicol Clin Tox 1996;34(5):513-516. 

47. Seamon MJ, Clauson KA. Ephedra:yesterday, DSHEA, and 

tomorrow—a ten year perspective on the Dietary Supplement Health 

and Educatioin Act of 1994. J Herbal Pharmacother 2005;5(3)67-86. 

48. Schwartz RA. Eosinophilia-Myalgia Syndrome. eMedicine 2008. 


http://www.emedicine.com/derm/topic891.htm 

49. Turnipseed S, Casey C, Nochetto C, Heller DN. Determination of 

melamine and cyanuric acid residue in infant formula using LC- 

MS/MS. Laboratory Information Bulletin No 4421. FDA Laboratory 

Information Bulletin 2008;24. 

50. United States Department of Agriculture. Food Safety and Inspection 

Service. Accessed Dec 2008 from: 

http://www.fsis.usda.gov/Food_Defense_&_Emergency_Response/in 

dex.asp 

51. United States Department of Defense. Crisis Communication 

Strategies. Analysis: Case Study: The Johnson & Johnson Tylenol 

Crisis. DoD Joint Course in Communication Class 02-C, Team 1. 


http://www.ou.edu/deptcomm/dodjcc/groups/02c2/Johnson%20&%20 

Johnson.htm 

52. Wein LM, Liu Y. Analyzing a bioterror attack on the food supply: the 

case of botulinum toxin in milk. Proc Natl Acad Sci 

2005;102(28):9984-9989. 

http://www.pnas.org/content/102/28/9984.full 

53. Zernike K. “Arsenic Case Is Considered Homicide, Maine Police Say.” 

The New York Times, May 2 2003. 






54. de Zwart D, Kramer KJM, Jenner HA. Practical experiences with the 

biological early warning system “mosselmonitor”. Environ Toxicol 

Water Quality 2006;10(4):237-247. 


















Module Five 

Icon Map 






instruction 





Slide 1 


Module Five 

Chemical Contamination of 

Food, Water, and Medication 


1 

This module will focus on the delivery mechanism of industrial toxins disseminated 

through water, food, or medication. 





Slide 2 

This module provides an overview of the US food, drug, and water production systems 

with a view towards identifying potential threats and vulnerabilities. Past incidents of 

contamination or terrorism are discussed and used to contextualize existing or possible 

preventive measures and regulations. 

By the end of this module, participants should be able to: 

Describe how US drinking water is produced and protected 

Describe significant episodes of water, food, and medication contamination; noting 

potential agents of concern, system vulnerabilities, and resulting system-wide changes 

or legislation 

Identify resources detailing measures used to protect the US water, food, and drug 

supplies 





Slide 3 



Water Treatment 

• State / federal EPAs regulate public drinking water 

safety (Safe Drinking Water Act) in US 

• Common treatment steps: 

– Coagulation / Flocculation 

– Sedimentation 

– Filtration 

– Disinfection 

Module One - Chemical Contamination of Food, Water, and Medication 

3 

This module will present the steps involved for most of the U.S. population in bringing 

water from a reservoir or aquifer to the home or business. 

Federal and state Environmental Protection Agency (EPA) regulate pubic drinking water 

safety via the Safe Drinking Water Act. There are a number of water characteristics (e.g. 

turbidity – a measure of clarity) and contaminants (e.g. lead) that are regulated by 

maximum contaminant levels (MCLs). Although assays for nearly 100 contaminants are 

performed, there are many elements and compounds that are not regulated or 

measured. 

Some common steps used in the treatment of water to make it safe for drinking are 

coagulation/flocculation, sedimentation, filtration, and disinfection. 

The Safe Drinking Water Act was first passed in 1974, with the latest revision in 1996. 

This statute defines water qualities that are mandated for public drinking water. All 

“states” except Wyoming, the District of Columbia, and most tribal nations have 

“primacy”, meaning that the states take responsibility for complying with water safety 

standards. Federal EPA provides oversight and monitoring for the others. 

There are more than 170,000 community drinking water systems in the U.S., 

approximately 1/3 of those use ground water (wells/aquifers), while 2/3 originate from 

surface water (rivers, lakes, reservoirs). 

Each of the water treatment steps will be expanded in the next slides, but a basic 

definition includes: 

1. Coagulation/Floculation: adding alum or other agglomerating agents that cause large 

particulates to clump together 

2. Sedimentation: removal of larger particles by gravity 

3. Filtration: removal of small particles (potentially down to the micrometer size or smaller 

4. Disinfection: (usually with a chlorine containing compound in this country). The chlorine 

kills viruses/bacteria well, but spores & protozoa such as Giardia & Cryptosporidium are 





relatively resistant. In Europe, disinfection is done with ozone which is very effective but 

unlike chlorine, has no residual effects since it doesn’t stay in the water. This can lead to 

re-contamination during water storage or final routing to the tap. 





Slide 4 



Typical Public Drinking Water System 


4 

This slide shows a schematic or overview of a typical water system of the steps typically 

involved in the water treatment process from source to tap. Beginning from a water 

source, the water is first treated to remove large particles, then filtered for smaller 

particles, then disinfected. 





Slide 5 



Coagulation/Flocculation 


5 

Coagulation removes dirt and other particles suspended in water. Alum and other 

chemicals are added to water to form tiny particles called “floc” which attract the dirt 

particles. The combined weight of the dirt and alum (floc) become heavy enough to sink 

to the bottom during sedimentation. 

This step is the “first pass” at removal of contaminants and is important both for water 

clarity and safety. 





Slide 6 



Sedimentation 


6 

The heavy particles (floc) settle to the bottom and the clear water moves to the filtration 

stage. 





Slide 7 



Filtration 


7 

Water passes through filters, some made of layers of sand, gravel, and charcoal that 

help removes even smaller particles. 





Slide 8 



Disinfection 


8 

A small amount of chlorine, bleach, or chloramine is added (or some other disinfection 

method is used) to kill any bacteria or microorganisms that may be in the water. Once 

disinfecting agents have been added, the water is held in storage to allow disinfection to 

take place. The water then flows through pipes, to homes and businesses in the 

community. 

After chlorine is added to the water, some free residual chlorine remains. This provides 

continued antimicrobial action. A significant drop in free residual chlorine indicates either 

a lack of disinfectant input or a high chlorine demand – suggesting the presence of 

nitrates or other material in the water. 





Slide 9 



Water System Vulnerabilities 

The Water System, 

• Is essential for health & safety 

• Comprises spatially diverse elements 

• Is susceptible to intrusion 

• Provides numerous attack sites 

• Is difficult to protect against backflow attacks 

• Contamination is difficult to trace 


9 

The US public drinking water system is vitally necessary. 

It is spatially diverse providing numerous possible attack vectors and targets. 

Distribution systems are quite complex and the low pressure flow patterns are highly 

variable and difficult to predict. 

Many of the water pumps are custom built and, if damaged, would takes months to 

replace. Apart from providing potable drinking water, in most cities fire fighters depend 

on the public water system for fire control and suppression. 

These reasons, among others, make the US public drinking water system a tempting 

target for would be terrorists. Compared to other kinds of community assault, an attack 

on the water system would be particularly troubling. 





Slide 10 



Maple Leaf Reservoir (Seattle, WA) 

• Sept 10th, 2002 

• Breach of fence around 

60,000,000 gal finished water 

reservoir reported. 

• 15 foot garden hose found near 

cut in fence. 

• First noted 2 days earlier but not 

reported to supervisors. 


10 

On September 10 th of 2002 a breach in the fence surrounding the Maple Leaf Reservoir 

– a 60 million gallon reservoir serving the Seattle, WA area – was noted. A hose was 

found at the scene, near a cut section of perimeter fence. Despite the damage having 

been noted 2 days previously, no one had thought to report the incident to supervisors. 





Slide 11 



Questions 

When water supply adulteration is suspected, 

– What chemicals should we test for 

– Who can run STAT tests for 

significant chemical contaminants 

– What criteria do you use to say 

the water is safe to drink 


11 

In circumstances such as these, certain basic questions arise. 

How should a public health entity respond 

Should the reservoir be put off-line 

Should there be a PSA (public service announcement) 

Should a health survey (100,000’s people) be performed 

Should lab testing be done 

What should be tested 

What chemicals should we test for 

Who can run STAT tests for significant chemical contaminants 

What criteria do you use to say the water is safe to drink 





Slide 12 



Maple Leaf Reservoir (Seattle, WA) 

• Tests on hose and reservoir water negative 

• No claims of responsibility 

• No clusters of illness identified 

• Reservoir water disinfected and reprocessed 


12 

Despite extensive testing by HazMat and state health department officials, no 

contaminants were found in the reservoir water supply or on the hose. In addition no one 

sought to claim responsibility for the event and no unusual clusters of illness were 

identified in the reservoir’s catchment area. 

As a precautionary measure the reservoir was emptied, the water treated with chlorine, 

and refilled. 





Slide 13 



The Ideal Drinking Water Contaminant 

• Resists water treatment 

• Is difficult to detect 

• Is difficult to clean 

– Pipes, reservoirs, etc 

• Causes illness: 

– Delayed onset 

– Difficult to diagnose 

• Readily available 

• No odor & taste 

• Colorless 

• Water soluble 

• Stable in water 

(i.e., resistant to hydrolysis) 

• Unexpected 

• Low LD50 


13 

There are many features that could be used to define an ideal water contaminant. Some 

of them are common-sense, in order to avoid early detection. Most are important in order 

to evade some component of the water purification systems that are in place. Apart from 

simple accessibility, an ideal contaminant should: 

Be resistant to existing water treatment methods 

Be difficult to detect through routine surveillance/monitoring 

Be difficult to clean contaminated equipment 

Be colorless, odorless, and without taste 

Water soluble and water stable 

Should cause illness that is both unexpected, delayed in onset, and difficult to diagnose 

(i.e., non-specific symptoms/signs) 





Slide 14 



Relative Water Toxicity 

R = Solubility/Lethal Dose x 1000 

Compound 

R 

Botulinum Toxin 

10,000 

VX 

300 

Sarin 

100 

Nicotine 

20 

Cyanide 

9 

Amiton (OP) 

5 

Na Fluoroacetate 

1 

Arsenite, arsenate 

1 

Clark: J Contingencies Crisis Management 2000 


14 

Relative water toxicity is calculated as a ratio of an agent’s solubility to the dose required 

to cause death. A higher relative water toxicity value (R) indicates it would be easier to 

dissolve a toxic dose in water. 





Slide 15 



Cyanide Calculations 

Cyanide salts as potential contaminants: 

• Individual: 

– 250 mg Lethal Human Dose (oral) 

(250 mg/0.5 L = 500 mg/L = 0.5 g/L) 

• Water System: 

– 0.0005 kg/L x 200,000,000 L = 100,000 kg = 220,000 lb = 

110 tons 


15 

This is an estimated oral (not inhalational) lethal dose. Assuming that everyone drank a 

½ liter, 110 tons is the amount of cyanide salt that would be necessary to contaminate 

200,000,000 liters (60 million gallons) of water – obviously, this is a lot of cyanide and a 

somewhat impractical means of attack. 





Slide 16 



NaCN Tanker 


16 

Cyanide is a very commonly used industrial chemical and is widely available for use in 

the mining and metal refining industries. A tanker truck (as depicted here with the driver 

wearing protective clothing and a face shield, holding the large hose used to transfer 

cyanide) that is loaded with 30,000 gallons of 24-32% aqueous sodium cyanide solution 

carries roughly 8 tons of cyanide salt. 

While this is considerably less than the amount calculated to be necessary for 

contaminating an entire water system, the tanker company shown above delivers 39,000 

tons/year with a capacity more than double that amount. 





Slide 17 



Botulism Calculations 

• 0.00003 µg/kg LD50 Mice 

• 70 µg Lethal Human Dose 

• 70 µg/0.5 L = 140 µg/L 

• 140 µg/L x 200,000,000 L = 28,000 g 

• 28 kg for 200,000,000 L Reservoir! 


17 

Contrast the amount of cyanide necessary to poison a reservoir (110 tons) with the 

amount of extremely toxic botulinum toxin required. Roughly 60 pounds of botulinum 

toxin would be required to contaminate 200 millions liters (60 million gallons) of drinking 

water. 





Slide 18 



Filtration Spectrum 


18 

There are other forms of filtration beyond “particle level” filtration. This slide, provided by 

a General Electric subsidiary, shows relative particle size in relationship to filtration 

efficiency. The most effective method of filtering water for contaminants is reverse 

osmosis. This process can effectively remove even metals and dissolved salts. 

However, it is also expensive, requires frequent changes of the filters, must be used in 

association with other filtration methods (to minimize fouling of the membrane) and may 

be inefficient in terms of waste water generation. 

This chart provides information on relative particle size of different filtration methods. 

Examples of contaminants cleared at different levels include: 

1. gross contaminants (e.g. sand in the millimeter size range or coal dust and other air 

pollutants of the micrometer size) which are removed by particle-level filtration 

2. suspended or dissolved compounds (such as latex or other emulsions [globules of liquid 

suspended in the water], bacteria, tobacco smoke) which are removed by microfiltration 

techniques 

3. proteins (such as virus particles and albumin in the fractions of micrometer range) which 

are removed by ultrafiltration 

4. water-soluble molecules (such as sugars at the nanometer range) which are removed by 

nanofiltration 

5. dissolved elements (such as metals and salts at the fraction of a nanometer [equivalent 

to angstrom] range) which are removed by reverse osmosis. 





Slide 19 



Cross-Connections 

• Mix of non potable with potable water 

• Distribution system pressure ≥ 20 psi 

• Backpressure: external>system pressure 

• 1970-01: 459 events, 12,093 illnesses 

– Avg 1 line break/yr 1,000 person system 

(Potential Contamination Due to Cross -connections and Backflow and Associated Health Risks. 

Issue Paper US EPA OGW & DW Aug 2002) 


19 

Let’s turn our attention to another potential vulnerability in the drinking water system. 

This vulnerability occurs during water distribution, namely cross-connections. These 

represent opportunities to introduce contaminants into the potable water system by 

exceeding the pressure within the system (minimum of 20 psi, usually 2-3 x that 

pressure). 

A survey of 30 years of reporting to the EPA identified 459 events with over 12,000 

associated illnesses. These were predominantly infectious diseases from contaminated 

water leaking into water systems from old water pipes, valves or other connections. 

Nonetheless, these numbers point out the potential vulnerability of an aging water 

distribution system and the ease with which someone could intentionally contaminate a 

water supply. 

Unintentional water main breaks are reported to occur at a rate of approximately one 

incident per year for every 1000 persons served.. 

Over 50% of the drinking water pipes in the U.S. are over 30 years old and some 

systems use pipes that are more than 150 years old. Cross-connections can lead to 

contamination of the drinking water supply as pressures within the system fluctuate. 

Intentional cross-connections can occur by applying backpressure to a water system, 

introducing a toxin by tapping into the distribution line. Backsiphoning, another form of 

backflow, can occur when the water pressure in the system drops because of lowered 

input or excessive use at some point in the system. 





Slide 20 



Cross Connection / Backflow Threats 

One sociopath who understands hydraulics and 

has access to a drum of toxic chemicals could 

inflict serious damage pretty quickly to a water 

supply system in a neighborhood or a 

pressure zone without detection in most 

communities. - Denileon : JAWWA 2001 


20 

The vulnerabilities of the distribution system are highlighted by this statement in the 

Journal of The American Water Works Association. In this article, written before the 

2001 U.S. terrorist attacks, Ms. Denileon discusses several potential types of terrorists, 

their funding, and potential targets. She reaches a conclusion, shared by the EPA, that 

the cross-connection issue is the highest priority vulnerability within our water system. 



Cross Connection Example 

North Carolina (1997) 

• 60 gal. retardant foam pumped into hydrant 

• No local labs for testing 

• Water use ban on 40,000 households 

• 90 million gallons used to flush system 

• No drinking water for 39 hrs 

Krouse: Opflow 2001 


21 

In 1997, a mistaken cross-connection made by fire fighters in North Carolina caused 60 

gallons of fire retardant foam to be pumped into the local drinking water system. Firemen 





immediately began flushing nearby hydrants, a valve team was dispatched, and 

attempts were made to isolate contaminated part of distribution system. This incident 

impacted the water supply for some 40,000 households and caused foam to flow from 

fire station faucets. No local labs were available for testing and water usage had to be 

banned for the entire local area. Ninety million gallons of water was used to flush the 

system and, after 39 hours, the “all clear” was given to begin using the water again. 





Slide 22 



Drinking Water: Terrorism Detection 

Detection Scenarios: 

• Caught in the act 

(cameras, security, or eye witness reports) 

• Online/Field detection & monitoring 

• Water quality observations (odor, color, …) 

• Mass Illnesses (often nonspecific) 

– ED/Public Health Surveillance Systems 


22 

Currently there is no systematic evaluation of drinking water other than routine periodic 

testing required by the EPA. As should be clear from this presentation, there is no 

analytic test (and certainly no readily available test) to answer all questions about water 

quality or potential water contaminants. 

Since most water treatment and distribution facilities have some measure of security, 

many incidents may be detected by eye witness report, surveillance cameras, or – as 

with the potential Seattle case – detected by a perimeter breach. Barring the possibility 

of catching a culprit in the act of contaminating the water supply, detection of a terrorist 

attack would be dependent on noting obvious abnormalities of the water or an illness 

cluster detected by a public health surveillance system. 

Increases in over-the-counter sales for anti-diarrheals is one of the many components of 

BioSense, a public health surveillance system. Emergency Department or Poison Center 

syndrome/diagnosis tracking is another surveillance activity. Although rapid recognition 

of disease onset potentially provides early detection of disease clusters, this surveillance 

(secondary preventive measure) is obviously not an ideal preventive or mitigation 

measure. 





Slide 23 



Early Detection 

• Online Phys/Chem Monitors 

– Chlorine, pH, Turbidity, Total Organic Carbon, Pressure, 

Radioactivity 

• Rapid Field Testing Kits 

• Online Biosensors 


23 

There are devices that can be used to detect water contamination. However, they are 

not routinely used unless there is suspicion that something is wrong. 

Some biological and chemical contaminants may cause a drop in residual chlorine levels 

but a much more likely cause is a failure of the chlorination system. While a drop in 

residual chlorine, if detected, may provide evidence of a failure in disinfection, it is 

unlikely that changes in the physical or chemical properties of water could be used to 

detect chemical contamination. 

There is an ongoing discussion about ways to implement additional safeguards on a 

routine basis that could detect at least some agents with the potential to be used by 

terrorists. 





Slide 24 

A variety of biologically based sensors exist that capitalize on the sensitivity of organic 

systems (living organisms) to detect the presence of dangerous chemicals. Like the 

proverbial canary in a coalmine, observing these organisms’ reactions can provide 

valuable information regarding water-borne contaminants. Since the organisms used in 

these tests would be adversely affected by disinfecting chemicals, the tests must be 

performed on raw (untreated) water or after the disinfectant is chemically removed. 

In contrast to the field sensors mentioned in the prior slide (which would only be 

implemented when abnormalities were suspected), these on-line biosensors serve as 

active monitors, used continuously and alerting staff as soon as water quality issues are 

detected. Further investigation as to the specific chemical (or other) cause would be 

necessary, but precautions regarding use of the water could be taken immediately. 





Slide 25 



More Information 

Available Online at: 

www.epa.gov/safewater/security 


25 

For more information regarding water quality and planning for response to threats to the 

US drinking water system, the US Environmental Protection Agency provides a 

“Response Protocol Toolbox: Planning for and Responding to Drinking Water 

Contamination Threats and Incidents”. 





Slide 26 



Physician Preparedness for Acts of 

Water Terrorism 


26 

In addition, there is physician-oriented continuing medical education available on-line in 

the area of preparing for water-delivered chemical terrorism. This course is accessible to 

all at www.waterhealthconnection.org 





Slide 27 





Slide 28 

Turning to the U.S. food system, we should first note that the regulatory structure is not 

as clear as it is with the regulated drinking water system. The U.S. Food and Drug 

Administration (FDA) regulates roughly 80% (by number of items) of the U.S. food 

supply, including all foods except meat, poultry, and processed egg products. These 

latter items are regulated by The U.S. Department of Agriculture (USDA). 

The FDA and USDA have conducted a vulnerability assessment, identifying 4 factors 

that are consistently associated with foods at a higher risk for terrorism: large batches, 

uniform mixing, short shelf life, and ease of access. 

Slide 29 







Factors Enhancing Food System 

Vulnerability 

• Concentration of primary production in large, 

monoculture farms/stockyards 

• Raw goods from small suppliers combined 

• Concentration of commodity food -processing in 

large centralized facilities 

• Quality control not designed to detect unanticipated 

contaminants/poisons 


29 

The rationale for the food supply vulnerability assessment is highlighted here. Because 

raw foods including fruits, vegetables and meats are often shipped from all over the USA 

(and overseas) and, particularly in the case of meat products or milk, combined into 

large batches prior to shipping, any contamination could become widespread. 

Identification of abnormalities would be potentially impeded by sampling techniques 

(laboratory limits of detection as well as small samples) and the exact source may be 

difficult to identify, highlighting the vulnerability of the food system. 

Although no test can detect “everything”, the lack of quality control inspections for 

chemicals not anticipated to be present is a vulnerability that is highlighted by the 2007- 

2008 epidemic of melamine/cyanuric acid adulteration of pet food and infant formula. 

Identification and detection of these compounds did not occur until after repeated 

illnesses. The delay to distributing quality control instructions and laboratory methods, 

and uncertainty regarding “safe” levels, further complicated this situation. 





Slide 30 



Botulism Threat 

• Potency: “Most Lethal Substance ” 

– 70 ug Lethal Oral Dose 

– 70 gm Could Kill 1,000,000 People 

• Prolonged ICU Requirement 

– May Exhaust Supply of Ventilators 

• Easy to Mass Produce 

– Russia, Iraq, Iran, Syria, North Korea 

– 1991 “Iraqi Stockpile ”: 19,000 L 


30 

Let’s use botulinum toxin (produced by the bacterium, Clostridium botulini) as an 

example of a potent toxin being introduced into the food supply. Although not an 

industrial material (and considered as a Class A biological weapon by the CDC), it is 

produced in large quantities and available as a medication (Botox – botulinum A toxin). 

Because of the muscle paralysis (particularly respiratory muscle failure) that occurs with 

botulism, it has been estimated that 60% of botulinum poisoned individuals would 

require mechanical ventilation. Given the small number of ventilators and limited amount 

of antitoxin in the national stockpile, the death rate from a large attack would likely be 

closer to the pre-1950s mortality rate of 60%, or perhaps the 25% rate that occurred in 

the 1950s, rather than to the 6% death rate experienced in the 1990s. 

This agent has been weaponized by a number of nation-states, so we will use it as an 

example of a potential food contaminant similar to its use in the water portion of this 

module. 





Slide 31 

This slide depicts the mechanism of action of botulinum toxin – the end result being 

inhibition of acetylcholine (neurotransmitter) release. The toxin, once taken up by the 

nerve fibre (axon) ending, prevents the fusion of presynaptic vesicles containing 

acetylcholine (the neurotransmitter responsible for sending signals between the brain 

and the muscle) with the nerve membrane at the synapse (connection point between 

nerve and muscle). If no acetylcholine is released, then coordinated muscle activity does 

not occur. Thus patients with botulism have paralysis, and this paralysis lasts a long time 

(weeks - months) even with use of the botulinum antidote (antitoxin antibodies). 





Slide 32 




32 

Several years ago, a terror attack using botulinum in the milk supply was modeled, as an 

example of introducing a potent toxin into the food supply. 

The California dairy industry was chosen because this system produces 20% of the nation’s 

milk. 

Instructor Note: 

The pasteurized milk delivery system is characterized by the rapid distribution of 20 billion 

gallons per year in the U.S. There have been previous infectious disease outbreaks in the dairy 

industry including two natural Salmonella outbreaks, each infecting ~200,000 people. 

The findings from this National Academy of Science mathematical model form the basis for the 

next several slides. 

The major focus for the discussion in this portion of the module is the extent of poisoning that 

can occur with introduction of a small amount of a very toxic substance at the producer end of a 

“bow-tie” supply chain. By extension, introduction of larger amounts of a less toxic substance at 

the early part of the distribution side of the supply chain can have similar effects. This would be 

the case for most industrial chemicals that would be introduced into the food supply. 

Reference: 

Wein LM, Liu Y.Analyzing a bioterror attack on the food supply: the case of botulinum toxin in 

milk. Proc Natl Acad Sci 2005;102(28):9984-9989. 

http://www.pnas.org/content/102/28/9984.full 





Slide 33 




33 

This slide depicts the model used in this study. Many food products, such as milk, fruit 

and vegetable juices, canned foods (e.g., processed tomato products), grain-based and 

other foods follow the bow-tie-shaped supply chain pictured above. 

Introduction of a chemical at any point in the manufacture/collection and processing 

system to the left has the potential to contaminate all of the finished goods. 

Introduction of a chemical at any point in the distribution and sales portion of the food 

chain on the right hand side will contaminate less of the product and poison fewer 

individuals. This situation also allows easier identification of the site of adulteration and 

potential culprit. 

Adulteration at a “downstream” (distribution/sales) site allows effective use of a less 

potent chemical agent (than botulinum toxin). 





Slide 34 

In the model just depicted, the authors note that infiltration of the system anywhere on 

the “left-hand side of the bow-tie” with only 1-10 grams of botulinum toxin has the 

potential to poison 100,000 people to more than 5 times that number (i.e. all of the 

tainted milk consumers), if undetected. 

If a clinical surveillance system notes a signal and is correctly interpreted, 2/3 of the 

cases could be prevented by public notification and milk recall, yet 100,000 people could 

still be poisoned. 

The authors estimate the cost to care for 100,000 botulinum poisoned patients (even if 

that number of ICU-equivalent beds, ventilators, and anti-toxin were available) would be 

17.2 million dollars 





Slide 35 



Inactivating Botulinum Toxin 

• Botulinum toxin cannot be completely inactivated by 

radiation or any heat treatment that does not 

adversely affect the milk ’s taste. 

• Ultrahigh -temp pasteurization (UHT) can inactivate 

botulinum toxin but has not been embraced by U.S. 

consumers. 


35 

Botulinum toxin is difficult to destroy. Remember- in this model - it is not the bacteria 

(Clostridium botulini ) that needs to be killed, but the toxin itself that was maliciously 

added to the milk. 

In Ultra High temperature processing, the milk is heated using commercially sterile 

equipment and then placed into hermetically-sealed (airtight) containers under aseptic 

conditions. This high temperature is sufficient to inactivate practically all botulinum toxin. 





Slide 36 



Maine Arsenic Poisonings 

• 1 died, 15 others were sickened 

following Sunday services in 

2003 

• Next day, maintenance man died 

of gunshot wound to chest 

• Victims shared coffee and food 

• Arsenic was found in the coffee 

pot. 


36 

This event is an example of inserting a toxin at the point-of-use (end of the distribution 

chain). A dispute amongst members of a church resulted in one death and 15 others 

sickened after drinking coffee contaminated with arsenic and served after Sunday 

services. 

An individual with maintenance duties at the church (including making the coffee) 

committed suicide the next day, leaving a note implicating himself and possibly another 

individual. 

A tentative diagnosis of heavy metal poisoning was confirmed within a day and 

treatment with a chelating agent (dimercaptopropane sulfonate) begun for the affected 

individuals, who presented to the hospital hours after ingesting the coffee with stomach 

pain, nausea and vomiting, diarrhea, and low blood pressure. This event has had a 

lasting effect on this small community (population ~650), with the loss of a “sense of 

innocence” (suspicion, locking doors) documented in news articles years later. 





Slide 37 

In 1981, 20,000 people were poisoned by consuming adulterated rapeseed oil. 

This epidemic occurred because of adulteration of a falsely labeled cooking oil with an 

industrial dye (aniline) in the processing portion of the food chain for a large area of 

Spain. 

This poisoning resulted in 12,000 hospital admissions and over 300 deaths. Based on 

clinical reports the acute phase was a respiratory illness with patients exhibiting 

eosinophilic pneumonia, hypertension, and scleroderma-like changes. 





Slide 38 



How Safe are US Medications 

• Drug production is a complex process 

– Synthesis Delivery to the patient 

– Multiple steps for interference 

• Depending on the circumstances, the results can be 

devastating: 

– Primary Impact (fatalities, illness) 

– Fear/Uncertainty 

– Economic Impact 


38 

As a last potential mechanism for a terrorist attack in this module, let’s turn to our 

medication system. The US drug production system is large and complex involving 

multiple production and distribution phases; each providing many opportunities for 

interference. A terror attack could occur anywhere from the production of the raw 

materials to the packaging and distribution of the final product. 

An attack in this sector would certainly have devastating results including decreased 

availability of potentially lifesaving medication, fear of using medications, and an 

economic impact on many levels. 





Slide 39 



Tylenol Murders (Chicago, 1982) 

• 7 died from KCN laced 

Tylenol 

• 1-2 bottles per store 

•




Slide 40 



Copycat (1986) 

• Woman in WA state killed her husband with cyanide -laced 

pain killer 

• Attempted to cover her tracks by placing packages of 

poisoned Excedrin and Anacin capsules on the shelves of 3 

stores 

• Nickell was sentenced to 90 years in prison. 


40 

In 1986, Stella Nickell of Washington state killed her husband with cyanide-laced 

Excedrin in a plot to collect on his life insurance. Attempting to cover her tracks she 

placed similarly poisoned packages Excedrin and Anacin at three local stores. 

Based on video evidence, eye witness reports, and a particular contaminant found in all 

of the contaminated capsules, Nickell was apprehended and sentenced to 90 years in 

prison. 





Slide 41 



1983 

The Tylenol Bill 

"Tylenol Bill ” made malicious tampering with consumer 

products a federal offense. 

1989 

FDA established a national requirement for tamper 

packaging of over -the-counter products. 

• Triple-seal, tamper -resistant packaging now the 

norm. 

-resistant 


41 

After these prominent events, Congress, the Food and Drug Administration, and 

pharmaceutical manufacturers turned to the problem of packaging non-prescription 

drugs to prevent tampering and restore the public's faith in the products. 

In May 1983, Congress approved the "Tylenol Bill," making malicious tampering with 

consumer products a federal offense. 

By 1989, the FDA had established compliance language and posted final rules requiring 

at least one of several possible packaging modifications. 





Slide 42 

This is just one example of many, reflecting medication tampering during the 

manufacture or processing stage of production. 

In 1996 an unusual cluster of renal failure cases was noted among children in Haiti. This 

lead to an investigation (described on the next slide) that eventually identified DEGcontaminated 

acetaminophen elixir as the cause. 





Slide 43 

In late 2007, reports began to come by MedWatch and other reporting mechanisms 

identifying severe allergic reactions and decreased blood pressure with more than 80 

deaths associated with administration of one brand of heparin (a blood thinning agent). 

Laboratory identification of a contaminant that had some anticoagulant activity led to the 

recall of this product. 

As with many recent events, a source of raw material from China, was found to be 

responsible. 





Slide 44 

In an effort to give consumers more input into their health management, President 

Clinton signed the Dietary Supplement Health and Education Act (DSHEA) in 1994, 

removing dietary supplements from any treatment as food (or drugs). While the FDA 

could still investigate reports of harm, all aspects of manufacture, claims and advertising 

were now left to the product producers. A notation was required that “this statement 

[regarding the use of the product] has not been evaluated by the FDA. This product is 

not intended to diagnose, treat, cure, or prevent any disease.” 

Since that time a number of dietary supplements, most notably ephedra-containing 

products, have been investigated or removed from the market because of documented 

safety concerns and/or adulteration. 

Asian patent medicines (traditional Chinese medicines) have been studied in market 

sampling surveys. 1/3 contain undeclared pharmaceutical agents, including some 

medications banned for human use. A variety of heavy metals (lead, mercury, arsenic) 

occur in these and other ethnic medicines. 

In 2008, the FDA received reports of illness attributed to excess selenium and chromium 

in one brand of dietary supplement through incorporation of too much of these 

ingredients in the manufacturing process. 

The unregulated foreign market and internet as a source of medication is another 

potential mechanism for introduction of contaminated products. 





Slide 45 

Due to the large number of individuals who depend on them, modern large-scale 

production and distributions systems for food, water, and medication provide a tempting 

target to would-be terrorists. 

The use of potent toxins or common industrial solvents can occur at multiple sites in the 

manufacturing, processing or distribution/sales chain. 

Past cases of tampering have resulted in closer government oversight and strict product 

safety and distribution standards for the US. 

Unusual case clusters or increased incidence of illness or disease out of keeping with 

local norms can be an indication of point source exposure to a toxic agent. While this is 

not the ideal method of detection (because of the delay to recognition), it is historically 

the only method that has been used to identify contamination. 

As we have shown in this module, there are a number of monitoring and safety steps 

that are being used to drastically limit the likelihood of large-scale terrorist attacks using 

the food, water or medication delivery system. Continued attention to safety and 

security of raw materials and processes will have benefits in preventing accidental 

contamination as well. 





Slide 46 





Module Five Summary 

Due to the large number of individuals who depend on them, modern large-scale production and 

distributions systems for food, water, and medication provide a tempting target to would-be 

terrorists. 

State and federal EPAs bear the primary responsibility for safeguarding the US public water 

supply. Water treatment steps commonly employed in the US include coagulation/flocculation, 

sedimentation, filtration, and disinfection. While chlorine used during the disinfection process 

kills viruses and bacteria, other biological contaminants and many chemical agents may remain 

unaffected. 

Due to their size and complexity, US water distribution systems are vulnerable at multiple sites. 

Though numerous layers of protection exist (testing, physical security, public reporting, health 

surveillance), US public water systems remain susceptible to contamination through adulteration 

or cross-connection/backflow. 

While not routinely used in day-to-day monitoring, a wide variety of tools exist for the early 

detection of chemical and biological contaminants in drinking water. Improved water supply 

safety will depend, in part, on the judicious application of these tools as part of a broader water 

quality surveillance plan. 

The US food supply is largely overseen by the FDA with some agricultural products, such as 

meat, milk and eggs, monitored by the USDA. The combined trend toward large monoculture 

farms, mixing of raw goods from multiple sources, and centralization of production increases the 

reach and potential impact of an attack. More rigorous and uniform quality control standards are 

being implemented to ensure the continued safety of the US food supply. 

Past cases of drug tampering have resulted in closer FDA oversight and strict product safety 

packaging standards for the US pharmaceutical industry. While historical examples of 

accidental drug contamination point to the potential impact of such events, the numerous 

safeguards enacted in recent years drastically limit the viability of a large-scale terrorist attack. 

However, the potential for an attack via other routes, such as the unregulated “dietary 

supplement” or internet-based/international medication market is increasing. 





Module Six 

Terrorism through Fear & Uncertainty: Delayed Toxic 

Syndromes - Administration Page 

Exposure to some chemicals is characterized by a delayed onset of toxicity which may make 

them attractive for use as a covert weapon. This delay of onset of symptoms complicates the 

epidemiology of the event, making detection and identification of the chemical (figuring out the 

cause of the problem and source), response and clinical management significantly more 

difficult. 

More people may be exposed to delayed-onset toxins and the individual’s dose may be larger, 

given the relative absence of warning properties to indicate exposure. In acute-onset toxins, 

most people will escape when they realize that others around them are developing symptoms. If 

however, no one is becoming ill, no one realizes they are being poisoned…and thus, no one 

takes the necessary measures to limit exposure. 

Chemical agents with a delayed onset can be organized and separated based on route/scenario 

of exposure. Some are airborne (phosgene), food and waterborne (thallium, organomercurials, 

radionuclides/radioactive metals), and environmental/biopersistent agents (dioxin, PCBs). 

Treatment depends on rapid identification and intervention and strategies will vary based on the 

class of chemical agent used. 

Duration 

45 minutes 


This module will introduce industrial chemical toxins which, due to their delayed onset of 

symptoms, may make them likely to be used as a covert weapon by terrorists. A framework is 

provided for organizing and separating these chemical agents based on their route of delivery 

and likely scenarios of exposure, as well as relevant toxidromes. 


• Understand the unique threat posed by exposure to chemicals which 

are manifested by delayed onset of symptoms. 


Resources 

• Recognize that exposure to some chemical agents does not result in 

the immediate onset of symptoms. 

• Describe the major chemical agents that may cause delayed toxic 

syndromes. 

• Differentiate between clinical presentations of various delayed-onset 

syndromes from these chemicals. 













1. Amin-Zaki L, Elhassani S, Majeed MA, et al. Intra-uterine 

methylmercury poisoning in Iraq. Pediatrics 1974;54(5):587-595. 

2. Agency for Toxic Substances and Disease Registry. Medical 

Management Guideline for Mercury. Accessed Dec 2008 from: 

http://www.atsdr.cdc.gov/MHMI/mmg46.html 

3. Agency for Toxic Substances and Disease Registry. ToxFAQs for 

Thallium. Accessed Dec 2008 from: 

http://www.atsdr.cdc.gov/tfacts54.html 

4. Bakir F, Damluji SF, Amin-Zaki L, et al. Methylmercury poisoning in 

Iraq. Science 1973;181(96):230-241. 

5. Bertazzi PA, Bernucci I, Brambilla G, et al. The Seveso studies on 

early and long-term effects of dioxin exposure: a review. Env Health 

Persp 1998;106 (S2):625-633. 

6. Centers for Disease Control and Prevention. Third National Report on 

Human Exposure to Environmental Chemicals. Atlanta (GA): CDC, 


http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf 

7. Clarkson TW, Vyas JB, Ballatori N. Mechanisms of mercury 

disposition in the body. Am Industrial Medicine 2007; 50(10):757-764. 

8. Cavanagh JB. What have we learned from Graham Frederick Young 

Reflections on the mechanism of thallium neurotoxicity. Neuropath 

Appl Neurobio 2007;17(1):3-9. 

9. Coenraads PJ, Olie K, Tang NJ. Blood lipid concentrations of dioxins 

and dibenzofurans causing chloracne. Br J Dermatol 

1999;141(4):694-697. 

10. Conradi P. “Prisoners were used to test poisons”. TimesOnLine, 

October 10 2004. Accessed Dec 2008 from: 

http://www.timesonline.co.uk/tol/news/world/article492686.ece 

11. Emsley J. Elements of Murder: A History of Poisons. Oxford 

University Press, USA; 2005. 

12. Hoque A, Sigurdson AJ, Burau KD, et al. Cancer among a Michigan 

cohort exposed to polybrominated biphenyls in 1973. Epidemiol 

1998;9(4):373-378. 

13. Houts PS, McDougall MS. Importance of evaluating the context in 

which notification occurs. AM J Industr Med 2007;23(1):205-210. 





14. Hsu J-F, Guo Y-L, Yang S-Y, Liao P-C. Congener profiles of PCBs 

and PCDD/Fs in Yucheng victims fifteen years after exposure to ricebran 

oils and their implications for epidemiologic studies. 

Chemosphere 2005;61(9):1231-1243. 

15. International Agency for Research on Cancer. Overall Evalutions of 

Carcinogenicity in Humans: List of all agents, mixtures, and 

exposures evaluated to date. Accessed Dec 2008 from: 

http://monographs.iarc.fr/ENG/Classification/crthalllist.php 

16. “Iranian Refugees at Risk” in Iranian Refugees’ Alliance Quarterly 

Newsletter (Summer/Fall 1997). Accessed Dec 2008 from: 

http://www.irainc.org/text/nletter/su97fa97/su97fa97.html 

17. Kulig K. A tragic reminder about organic mercury. N Engl J Med 1998; 

338(23):1692-1694. 

18. Kuratsune M, Yoshimura T, Matsuzaka J, Yamaguchi A. Epidemiolgic 

study on yusho, a poisoning caused by ingestion of rice oil 

contaminated with a commercial brand of polychlorinated biphenyls. 

Env Health Persp 1972;1:119-128. 

19. Landrigan PJ, Wilcox KR Jr, Silva J Jr, et al. Cohort study of Michigan 

residents exposed to polybrominated biphenyls: epidemiologic and 

immunologic findings. Ann New York Acad Sci 1979; 320:284-294. 

20. Leung HW, Kerger BD, Paustenbach DJ, et al. Concentration and 

age-dependent elimination kinetics of polychlorinated dibenzofurans 

in Yucheng and Yusho patients. Toxicol Industr Health 

2007;23(8):493-501. 

21. Masuda Y. The Yusho rice oil poisoning incident in Dioxins and 

Health. Schecter A and Gasiewica TA (eds), 2nd ed; John Wiley & 

Sons, Inc., Dallas TX 2003. 

22. Meggs WJ, Hoffman RS, Shih RD, Weisman RS, Goldfrank 

LR.Thallium poisoning from maliciously contaminated food. J Toxicol 

Clin Toxicol 1994;32(6):723-30. 

23. Nierenberg DW, Nordgren RE, Chang MB, et al. Delayed cerebellar 

disease and death after accidental exposure to dimethylmercury. 

NEJM 1998; 338(23):1672-6. 

24. OSHA. Hazard Information Bulletin – Dimethylmercury. February 15 


http://www.osha.gov/dts/hib/hib_data/hib19980309.html 

25. Reich MR. Environmental politics and science: the case of PBB 

contamination in Michigan. Am J Pub Health 1983;73(3):302-313. 

26. Schecter A, Birnbaum L, Ryan JJ, Constable JD. Dioxins: an 

overview. Environ Res 2006;101(3):419-28. 

27. Schwartz LM, Woloshin S, Fowler FJ, Welch HG. Enthusiasm for 

cancer screening in the United States. JAMA 2004;291:71-78. 

28. Steenland K, Bertazzi P, Baccarelli A, Kogevinas M. Dioxin revisited: 

developments since the 1997 IARC classification of dioxin as a 

human carcinogen. Env Health Persp 2004;112(13):1265-1268. 






29. United Nations Environment Programme. Dioxins, Furans, Pose 

Concerns for Health and Environment World-Wide. 1999. Accessed 


http://portalserver.unepchemicals.ch/Publications/InfDioxinsJuly99.pdf 


















Module Six 

Icon Map 






instruction 





Slide 1 


Module Six 

Terrorism by Fear and Uncertainty: 

Delayed Toxic Syndromes 


1 

This module will introduce industrial chemicals that cause delayed onset of symptoms 

following exposure, making them an attractive covert weapon to terrorists. 

A framework is provided for organizing and separating these chemical agents based on 

their route of delivery and likely scenarios of exposure, as well as by their toxidromes. 





Slide 2 

This module introduces a very interesting group of chemicals – those that do not cause 

immediate symptoms. The concept of delayed onset chemicals may be particularly 

attractive to some terrorists as they mimic the time course of some biological agents. 

This module will go through examples of toxic industrial chemicals that present in very 

characteristic fashion, but days, weeks or even years following exposure, rather than 

those with immediate onset as we have been discussing for much of the morning. 





Slide 3 

Unlike the general concept of chemical poisoning, in which the onset of symptoms is 

rapid and the source identifiable, exposure to some chemicals present with a delayed 

onset of symptoms. This unique property could contribute to their use as a covert 

weapon. 

Allowing time to escape may not have an immediate impact (as is commonly seen with 

explosive terrorist events)., However, this delayed onset complicates the epidemiology 

(figuring out the cause of the problem and source) and makes clinical management more 

difficult. 

More exposures may occur because there are no warning properties of exposure. In 

acute onset toxins, most people will escape when everyone around them develops 

symptoms. But if nobody gets ill….nobody realizes they are being poisoned….and 

nobody escapes. 

For toxins with particularly long latency (delay to onset of symptoms or disease), such as 

those chemicals that may cause cancer, the long-term psychological effects may be very 

consequential, even in the absence of any physical disease. This is a reasonably good 

definition of terror. 

Delayed onset toxins may mimic biological agents (particularly non-contagious ones 

such as anthrax), both because of the time to symptom development (often measured in 

days-weeks) and the somewhat non-specific nature of initial symptoms. This further 

complicates the diagnosis. 





Slide 4 



Thallium salts 

• Qualities for unintentional and malicious use 

– Tasteless and odorless 

– Salts are water -soluble 

– Rapidly absorbed (oral, inhalation, dermal) 

– Not detected on routine toxicological screening 

– Highly toxic and easily concealable 

– Lethal dose ~10 -20 mg/kg (about 1 gram in an adult) 

– Inexpensive (~$1 -2 per gram) 

Module One - Terrorism by Fear and Uncertainty: Delayed Toxic Syndromes 

4 

Thallium has many qualities that allow it to be used as a terrorist weapon, as well as a 

long history of use as a homicidal toxin. 

In addition to being easy to conceal because of its water solubility and lack of taste and 

odor, it is rapidly absorbed by all routes of exposure and is not detected on any 

routinely-performed screening test; a specific thallium determination must be ordered 

and run on specialized instruments. It is toxic in very low quantities and very 

inexpensive. 





Slide 5 



Thallium Poisoning 

• Classic Triad: 

– Gastrointestinal distress (N/ V/ D) within a few hours, mild 

– Painful polyneuropathy (severe pain in the extremities) 

• About 24 hours after exposure, dose dependent 

– Hair loss; usually 2(+) weeks after exposure 

– Other: constipation, hypertension, EKG changes 

• Diagnostic testing 

– Abdominal x -rays may show metal 

– Blood thallium > 100 µg/L, urine thallium greater than 200 µg/L 

considered toxic 


5 

The “classic triad” of thallium poisoning is gastrointestinal symptoms, followed in a day 

or two by very painful distal extremities (especially soles of the feet), and after a delay of 

another 1-2 weeks, hair loss (alopecia). A history of recent severe nausea, vomiting, 

and diarrhea is an important clue to thallium (or arsenic) in patients who present with 

acute painful neuropathy and/or progressive diffuse hair loss. 

Thallium is a metal; therefore it may appear as a radiopaque density on an x-ray of the 

abdomen. However, from a practical point of view, patients rarely present early enough 

for this to be a useful diagnostic tool.. 

Blood thallium can be measured in reference laboratories. The test is not available in 

most hospital labs. 

. 





Slide 6 



Thallium-Tainted Marzipan 

• Four young adults in NYC 

share premium marzipan 

candies recieved by mail 

from an “unknown admirer ” 

• The next day they 

developed diarrhea, 

vomiting, abdominal cramps 

and constipation 

J Toxicol Clin Toxicol. 1994;32:723 -30. 


6 

This is one example of the thallium poisoning. 

Four young adults received a box of candy from an unidentified “admirer”. They shared 

3 candies (as can be seen in the photo of the uneaten portion above). The following 

day, they developed significant gastrointestinal distress, although somewhat varied in 

nature and severity. They came to an Emergency Department for evaluation. 





Slide 7 



Thallium-Tainted Marzipan (cont.) 

• After 2 days the two who ate most (a whole candy 

each) developed pain in the palms and soles worse 

with touch 

– Hypertension in and EKG changes in two 

– Three of 4 developed alopecia (hair loss) 


7 

Gastrointestinal symptoms resolved, but a very painful paresthesia (abnormal sensation) 

developed – so intense as to be painful with any pressure (even bed linen) against the 

distal extremity skin. After about one week, symptoms progressed to involve diffuse hair 

loss, with additional cardiovascular signs in the two who had consumed the most. 





Slide 8 



Thallium Poisoning 

• X-rays of the candies showed abnormal radioopacity 

• Lethal dose of thallium in each candy 

– Lab confirmed that each candy contained 810 to 1090 mg 

thallium 


8 

Routine X-Ray of the remaining candies showed variable amounts and lack of uniformity 

of radiodense material (opaque on X-Ray) that would be unusual in normal candy. 





Slide 9 



Jilted admirer, Filip Semey, arrested in Belgium 


9 

One of the involved women had been harassed by a man who had a history of stalking 

women. Investigators found he had left the country. A couple weeks later, he was 

arrested at his home in Belgium, tried and convicted. 

The newspaper clipping (New York Times) above shows an investigator holding a 

display of the adulterated candy and X-Rays and an inset photograph of the poisoner, 

Filip Semey. He had also sent a box of candy to another woman on the West Coast, 

and as mentioned above, had a history of stalking women. 





Slide 10 



Malicious Thallium Poisoning 

Other cases 

• 1971: Graham Frederick Young kills two co -workers 

– Liked to poison people 

• 1988: George Trepal kills Peggy Carr 

– Tainted Coca -Cola; 7 others poisoned, 2 became ill 

– Kids playing loud music, and dogs chasing his cats 

• 1988 and 1995: Iraqi dissidents poisoned 

– 1988: Abdullah Rahim Sharif Ali killed 

– 1995: Maj Safa al-Battat; presumably recovered 

• 1997: Kurds poisoned by Iranian agents 

– 60 sickened; presence of thallium confirmed 


10 

Thallium has a long history of use by both “crazy” people like Graham Frederick Young, 

who poisoned his friends and coworkers in England (he is the basis of the Young 

Poisoner’s Handbook - a book and a movie) and by “crazed” people who perform 

political or military assassinations. Graham Frederick Young was hospitalized as a 

teenager as criminally insane after fatally poisoning his pets and step-mother, and 

poisoning his father and sister, and classmates. He was released after convincing an 

examining psychiatrist of his mental health, then went on to poison co-workers with 

thallium added to tea. The workplace used thallium in the manufacturing of camera 

lenses (John Hadland Laboratories in Bovington, Hertfordshire). A consulting toxicologist 

became suspicious. When arrested by police, they found incriminating diaries tracking 

the progression of symptoms in his victims. He died in prison, reportedly of a heart 

attack, at the age of 42. 

George Trepal, a member of Mensa, after becoming angry at his noisy neighbors, 

poisoned them with thallium added to soda. He is currently on death row in Florida. 

Thallium was also used to kill Iraqi dissidents. These two individuals represent some of 

the many killed under Saddam Hussein’s reign. Some were poisoned by beverages or 

food given as a “token of reconciliation” at the time of their release from prison, only to 

die days-weeks.later. 

Cross-border chemical terrorism in the Persian Gulf region has occurred on a large 

scale. Smaller-scale events via poisoned food supplies occurred in the last decade, and 

as seen on the next slide, continue to occur now. 





Slide 11 

In March 2007 a mother and daughter, born in Russia but living in the US, were 

“accidentally” poisoned by thallium during a trip to Russia. 

They returned to the US for therapy and did well. 

This came on the heels of the Litvenenko case (by Polonium-210 poisoning) which was 

originally thought to be a case of thallium poisoning; and demonstrating the ongoing use 

of stealth (delayed-onset) agents in assassination plots. 





Slide 12 



Treatment 

• Multi-dose activated charcoal 

– Prevents absorption 

– Enterohepatic circulation 

• Prussian Blue ( Radiogardase ) 

– Prevents absorption from GI tract 

– Undefined efficacy 

• Unclear role for chelators once thallium is absorbed 


12 

Treatment for thallium poisoning involves efforts to prevent its absorption or hasten 

elimination. Thallium can be bound to either activated charcoal or Prussian Blue 

preventing its absorption through the GI tract. 

In addition, there is some recycling of thallium back into the gastrointestinal tract via the 

bile, where it can be bound to these therapeutic agents, if they are present in the 

duodenum, preventing reabsorption. 

Once thallium has been distributed to the rest of the body, it is unclear if any chelating 

agents would play a role in hastening elimination. 





Slide 13 



Three forms of Mercury 

Elemental 

(Hg 0 ; quicksilver) 

Liquid: essentially nontoxic by ingestion 

Vapor: brain and lung toxicity 

Inorganic salt 

(Hg 2+ ) 

Organic 

(Methyl-Hg) 

Typically rapid onset of GI effects when ingested 

Aryl (cyclic): behave like inorganic 

Alkyl (short -chain): methylmercury , ethylmercury , 

dimethylmercury 


13 

Mercury provides an example of an agent to use to raise fear and concern. Mercury 

exists in several forms. The particular physical state of mercury determines its toxicity 

and how the body handles it. 

Elemental mercury is of minimal toxicity in liquid form, but when inhaled following 

volatilization it can produce lung damage and neurotoxicity. Although low level exposure 

to a vapor over a long period of time can produce neurotoxicity without pulmonary 

abnormalities, this would not be as useful to a terrorist as would organic mercury (see 

below). 

Mercury salts produce corrosive gastrointestinal effects when ingested. There are no 

other realistic routes of poisoning than the oral route for mercury salts. Although this has 

been used in individual cases, it would not be effective in a large scale release. 

Organic mercury is the most concerning form of mercury, from a terrorism perspective. 

The neurotoxicity that it causes is similar to that of inhaled elemental mercury, but the 

ability of the short chain organic mercury compounds to be absorbed orally, to be 

inhaled, and to cross the dermal barrier raise concerns for its nefarious use. 





Slide 14 



• Uses: 

Organomercurials 

– Bactericidal, fungicides, paper manufacture, laboratory 

standard 

• Generally well absorbed by all routes 


14 

Organic mercury compounds (those in which Hg is bound to a carbon backbone) have 

been widely used in industry and science in very small concentrations. At a sufficient 

dose, organic mercury is the most toxic form of mercury... 

Depending on the specific organic mercury compound, absorption can occur by virtually 

every route, including dermal. 





Slide 15 



Dimethymercury 

Properties 

• Colorless, dense, volatile liquid 

• Readily absorbed through the skin 

• Rapidly penetrates latex gloves 

• Lethal dose approx 400 mg (5 mg/kg) 

• 10 grams = $183.80 


15 

This is one example of an organic mercury compound that is of extremely high toxicity. 

Dimethylmercury is used as a nuclear magnetic resonance standard in industry and 

research laboratories. 

Although less volatile than water, vapor exposure to methylmercury is still a significant 

route of exposure, particularly in settings of elevated temperature. 

This short-chain alkyl form of mercury passes through several types of glove material 

(latex, vinyl, neoprene), and the skin very easily. 





Slide 16 




16 

. 

Case Study: A 48 year old chemistry professor at Dartmouth College spilled a drop of 

methylmercury on her gloved hand while working under a hood in August 1996. She 

removed the glove, washed her hands, and noted the incident in her logbook. She 

presented about 5 months later with a progression of symptoms. 





Slide 17 



Dimethylmercury Toxicity 

Dr. Karen Wetterhahn 

• Day 0 : Spills few drops on latex -gloved hand 

– Initially asymptomatic and continued normal activities. She deli vered a 

paper at an overseas conference 3 months later. 

• Day 154: Onset of symptoms 

– Balance, gait and speech problems 

• Day 159: Admitted to hospital; symptoms progress 

– Paresthesias; visual field changes; bilateral high -pitched tinnitus; 

deterioration of speech, hearing, gait, mental status 

• Day 176: Persistent vegetative state 

• Day 298: Dies 


17 

Dr. Wetterhahn presented for evaluation in Jan 1997 (159 days after exposure) with a 

five-day history of progressive deterioration in balance, gait, and speech. A preliminary 

laboratory report indicated that the whole-blood mercury concentration was more than 

1000 µg per liter. 

Chelation therapy with oral succimer (10 mg per kilogram orally every eight hours) was 

begun on day 168 after exposure. 

She had aggressive chelation therapy and other treatments, but she died on June 8, 

1997, 298 days after exposure. 

The delay to onset of symptoms is remarkable in this case, presumably reflecting the 

time to distribution to the blood from an amount absorbed through the skin. 

The symptom complex described – affecting the brain, including the cerebellum (balance 

and gait), the cerebral cortex – higher level functioning (speech, hearing, “coning in” of 

visual fields – loss of peripheral vision, and change in mental status – vegetative state 

being unable to communicate or respond to stimuli) as well as peripheral nerves 

(paresthesias – abnormal sensation) is characteristic of the effects of mercury on the 

nervous system. 





Slide 18 



Dimethylmercury Toxicity 

Dr. Karen Wetterhahn 

• Initial blood mercury level: 

– 4,000 mcg/L 

– nl 1-5 mcg/L; toxic > 200 

• Chelated with DMSA 

• Exchange transfusion 

• No other Hg source identified 

http://www.dartmouth.edu/~toxmetal/TXQAcr.shtml 


18 

Laboratory values returned 169 days after exposure from sampling a week earlier: 

whole-blood mercury, 4000 µg per liter (normal range, 1 to 8; toxic level, >200); 

urinary mercury, 234 µg per liter (normal range, 1 to 5; toxic level, >50). 

An intensive investigation including sequential sampling of hair to identify the time of 

exposure, identified no other plausible source of mercury exposure. 





Slide 19 



N Engl J Med 1998; 338:1672 -1676 

Dr Wetterhahn ’s 

Cerebellum 


Age-Matched Woman 

19 

The effects of dimethylmercury toxicity are visible at the gross anatomy level. These 

autopsy pictures depict the volume loss in the cerebellum of Professor Wetterhahn (on 

the left) compared to a normal cerebellum of an age-matched woman (on the right). 





Slide 20 



Methylmercury Poisoning 

Iraq, 1971-1972 

• Wheat crop failure in 1970 

• Sept to Nov, 1971 govt distrib mercury treated crops 

– 73,201 metric tons wheat 

– 22,262 tons barley seed 

• Seed intended for planting 

– Methylmercury added to grain seeds as an antifungal 

– Warning in English 

– Shipment received after planting 

• Grain used to make flour rather than plant it 

– MeHg content 9.1 mg/kg (range 4.8 -14.6) 


20 

Other forms of organic mercury may also be toxic in a delayed fashion following acute 

short term exposure. 

A famous example is this unintentional poisoning event in Iraq in the 1970s. 

USAID (United States Agency for International Development) supplied seed grain to 

Iraqi farmers following a couple of wheat crop failures. 

Methylmercury was added to the grain as a fungicide to protect it from deterioration prior 

to planting. However, the grain was not distributed until after the planting season. 

Although there was a warning on the bags not to eat the grain, the warning was in 

English and Spanish, not Arabic. 

The hungry population ground the unplanted seeds to make flour for bread and were 

exposed to about 9 mg of methylmercury per kilogram of flour. 








Iraq, 1971-1972 

• Mean exposure period was 32 days. 

• ∼40,000 exposed over several months 

– Est. total MeHg dose was 80 to 250 mg. 

• 6530 hospital admissions / 459 hospital deaths 

• Latency to onset of ≈ 2 to 6 weeks 

• Initial lack of symptoms among animals fed grain 

may have instilled false sense of security that it was 

safe to eat 


21 

The contaminated bread was eaten by the population for an average time period of one 

month. 

Approximately 1% of those exposed (and 6% of those ill enough to be admitted to the 

hospital) died. 

Onset of symptoms was several weeks after consumption began. 

. 





Slide 22 




Clinical Findings in Adults 

• Numbness around the mouth and in a stocking -glove 

distribution 

• Classic Triad 

– Ataxia - slight unsteadiness to inability to walk 

– Visual changes ranging from blurred or decreased vision to blind ness 

– Dysarthria - Slurring of speech 

• Mental deterioration 

• Severity of signs and symptoms are dose -dependent 

– Mild/moderate symptoms: 2.4 mg/kg 

– Severe symptoms: 3.6 mg/kg 


22 

The symptoms developed by Iraqi adults follow the typical progression for organic 

mercury poisoning. 

Initial numbness (paresthesias) around the mouth and distal extremities was followed by 

the triad of gait abnormalities, visual, and speech changes. 

Most toxins exhibit a dose-response relationship. Comparing clinical effects with 

estimates of methylmercury consumption from contaminated grain were consistent with 

a dose-response relationship. 





Slide 23 




Developmental Toxicity 

• Crosses placenta and accumulates in child 

• Transmitted mother to child via breast milk 

• Severe developmental delay / Cerebral - 

palsy-like syndrome 

• Mother may have minimal or no symptoms 


23 

The developing nervous system of the fetus and infant is particularly vulnerable to shortchain 

organic mercury compounds. . As a toxin that interferes with cellular, particularly 

neuronal, development, the presentations in neonates who had been exposed included 

severe developmental delays and cerebral palsy – like syndromes of incoordination and 

weakness/spasticity. 





Slide 24 



Organomercurials – Potential 

Advantages in Toxic Terrorism 

• Toxic to humans in small amounts 

• Symptoms occur days to weeks after ingestion, 

depending on the dose 

• Highly fetotoxic, cross the placenta most readily of 

all forms of mercury, enter breast milk 

• Enter the body via ingestion of contaminated 

foodstuffs, inhalation and dermal exposure 


24 

Features of organomercurials that would be appealing for terrorist use include its toxicity 

in small amounts (1/2 gram or less), its impact on the very young and not yet born 

(“second generation impact”), the delay to detection because of delayed-onset 

symptoms and possible diagnostic uncertainty, and the possibility of using a variety of 

routes of exposure – making it both more difficult to identify the source, and therefore to 

eliminate it. 





Slide 25 



Seveso, Italy 

July 10,1976 

www.chm.bris.ac.uk 


25 

The last group of industrial chemicals with delayed onset toxicity that we will discuss 

today can be loosely grouped as complex halogenated aromatic hydrocarbons that are 

only very slowly broken down or eliminated from the human body once absorbed. These 

include such compounds as dioxin, a contaminant of “Agent Orange”. 

A chemical plant explosion and fire in 1976 released a massive amount of the 

biopersistent chemical dioxin into the environment. 





Slide 26 

This plant was involved in the chemical oxidation of a chlorinated aromatic hydrocarbon 

to trichlorophenol, an agricultural biocide and professional disinfectant. In the setting of a 

run-away reaction with increased temperature and pressure, a portion of the product 

released was a condensation product, usually known as dioxin. 

The mayor of the city was not notified immediately and the nature of the contaminating 

product generated was not known for days. 





Slide 27 



Unintentional Dioxin Release 

Immediate Events 

• Some residents with HA, nausea, eye irritation 

• Plants turn yellow; rabbits and chickens die 

• Day 6: 14 children to hospital “chemical burns ” 

• Day 10: Confirmed that dioxin was released 

• Day 16-23: Zone A evacuated 


27 

It took several days to understand the implications of the explosion and related health 

effects, even though the explosion was a known, overt event. The more than 2 week 

delay in response in terms of decreasing exposure by precautionary evacuation is 

notable. 

What if this chemical had been released in a covert fashion A presentation of the listed 

(in slide) delayed and dissimilar diagnostic features (other than the initial irritating effects 

of the smoke) affecting plants, animals, and children would not have an obvious unifying 

source and would be a source of great concern and potential panic. 





Slide 28 



Chloracne, Seveso, Italy 


28 

Despite the concern regarding dioxin and cancer initiation in animal models, the most 

consequential effect in humans appears to be severe cystic acne, known as chloracne. 

This disorder is not unique to dioxin, but can be caused by other halogenated aromatic 

hydrocarbons (e.g. aromatic organochlorine compounds). 

The acne is likely related to the release of dioxin into sweat glands following absorption, 

resulting in irritation and severe inflammation and infection. Scarring is common. 





Slide 29 



Seveso Chemical 

Plume 

Zone Size* 

Pop. 

A 0.3 804 

B 1.0 5941 

R 5.5 38,624 

Ref 28.8 182,843 

*Size in square miles 


29 

This map detail of the affected region of Italy pinpoints the ICMESA chemical plant, and 

provides an estimate of the areas of greatest contamination (A), lesser contamination 

(B), minimally affected areas (R), and an uninvolved area (Ref), with the size of the 

region (square miles) and population depicted in the chart . 

The zones are depicted in a plume model developed based on the meteorlogical 

conditions at the time of the release supplemented by data from soil sampling well after 

the release. Subsequent epidemiological studies attempted to correlate health outcomes 

with the areas in which people resided, until improved laboratory techniques allowed 

blood TCDD testing of these individuals. 





Slide 30 



Seveso, Italy: The Aftermath 

• Zone A cleaned and soil removed 

• Thousands of soil and blood 

samples collected 

• Surveillance Programs 

– Liver enzyme induction, lipid 

metabolism, congenital 

malformation, 

immunosuppression , chloracne 

(193 cases) 

– 20 years later TCDD blood levels 

still high 

– Increased female:male birth ratio 


Despite the limited human toll acutely (chloracne in about 200 people), and even with 

intensive follow-up demonstrating minimally statistically significant changes in other 

health effects, the financial (and psychological) toll was severe. Extensive environmental 

testing (depicted in top picture) and millions of tons of soil were carted away in cylinders 

(bottom picture) and stored. 

30 





Slide 



Unintentional Dioxin Release 

Controversial human effects 

• Many of the reported relationships between dioxin exposure 

and human toxicity have come under epidemiologic scrutiny 

• Carcinogenicity 

– Known carcinogen in mice and rats 

– In humans reported association with some cancers such as Non - 

Hodgkin ’s Lymphoma and soft tissue sarcomas but causation has not 

been established 

• Undisputed link between dioxin exposure and chloracne 


31 

The fear of carcinogenicity is the most important sociopolitical issue. However there is 

really no solid link of dioxins to human cancer despite its highly defined carcinogenicity 

in animal models. 





Slide 32 

Victor Yushchenko, while running for the Presidency of Ukraine, developed severe 

gastroenteritis after a dinner with political rivals.. It was later determined that he was 

likely poisoned at that time. The toxin was confirmed as dioxin by measuring tissue (fat) 

and blood levels. He had the second highest levels ever reported. 





Slide 33 

Notice the marked difference before (smooth skin) and after the exposure (pockmarked 

face), with significant recovery (but some persistent scarring) 3 years later. 





Slide 34 



“Yusho” Poisoning 

Japan, 1968 

• Kanemi rice oil contaminated with Kanechlor 400 

– Mixture of polychlorinated biphenyls (PCB) & polychlorinated 

dibenzofurans (PCDF) 

• 1788 certified exposures by end of 1982 

• Subacute symptoms: acne -like eruptions 

• Growth retardation in school children one year later 

– Triglyceride, immune & endocrine disturbances 

• PCDF may have played the greater role 


34 

Getting an organochlorine compound into the food supply on a larger scale is not 

unprecedented. This event involved nearly 1800 people in southern Japan. Although the 

rice oil (Yusho in Japanese) contamination was unintentional, it reminds us that an 

intentional poisoning could occur via a similar mechanism. 

This large scale disaster occurred 40 years ago when rice cooking oil was accidentally 

contaminated with a mixture of chlorinated hydrocarbons including PCBs and PCDFs. 

The major physical effect noted was an acne-like eruption (chloracne) preceded by 

eyelid swelling and increased eye discharge. Dark brown pigmentation of the skin and 

nails was also noted. Some lipid abnormalities and possible growth effects consistent 

with hormonal disruption were also noted in follow-up studies. 







Yusho Effects 


35 

In addition to the findings typical of chloracne, nail and gum changes were also noted 

after the Yusho event. 





Slide 36 



Chlorinated hydrocarbon 

Dioxin, PCB 

• Intentional mass exposure to dioxin or PCBs would 

be difficult to detect, induce wide -spread fear, and 

tax our resources for decades at an enormous cost 


36 

As mentioned, an intentional large-scale exposure to these biopersistent (slowly 

eliminated) compounds with potential or claimed long-term effects would be difficult to 

detect (other than the clue provided by those exposed to large amounts manifesting 

chloracne). 

A terrorist attack of this nature would have enormous financial and psychological impact 

for years; though few, if any, fatalities. 

The unintentional releases we have covered thus far are from other countries. 

Has such an event ever happened in the United States 





Slide 37 

Slide 39 



Forewarned Is Forearmed 

• Given a new willingness by terrorists in the 21st Century to 

use previously unthinkable means to meet their ends, we 

must prepare: 

– Limit access to highly toxic agents 

– Protections of food and water supplies, toxic substances in indu strial 

plants and in transport 

• Raise awareness of potential clinical effects to: 

– Hasten recognition 

– Limit exposure 

– Speed response 


39 

There has been an increase in terrorist activities over the last few decades in the setting 

of internal strife and in international settings. In an effort to prevent and prepare for the 

use of industrial chemicals as terrorist weapons: 

1. We must limit access to toxic agents, both those with rapid- and delayed-onset of 

symptoms. 

2. As has been increasingly recognized, hazard vulnerability analyses and system-wide 

protective measures must be developed and enforced. 





3. Improving our public health and medical response/care system is critical to prevent 

illness and save lives. One of the features of this response is the recognition of 

syndromes characteristic of exposure to chemicals and distinguishing those from other 

more common entities. 

Early recognition of illness clusters will limit the extent and number of exposures and 

allow for an earlier, appropriate response. 





Slide 40 



Lessons Learned 

• Highly toxic substances are currently readily available whose 

onset of toxicity is delayed 

• Toxins with delayed effects can be used to affect large 

numbers of people before it is discovered 

• The delay in onset of toxicity aids a would -be terrorist in 

avoidance of detection and escape 

• Widespread exposure and uncertainty re: long -term effects 

maximizes the fear factor – serves the purpose of the terrorist 

• Even less toxic compounds which are biopersistent and 

whose detection is delayed have enormous potential to 

cause fear and overwhelm health care resources 


40 

The examples covered in this module should make it clear that there are a number of 

available industrial chemicals that cause delayed-onset illness, allowing widespread 

exposure and potentially complicating clinical and epidemiologic evaluation. The more 

uncertain the source and long-term consequences of an exposure are, the more public 

fear (terror) will result. 

Because of the delay to onset of toxicity from a variety of available substances with 

significant potential to cause harm, many people may be affected – physically and/or 

psychologically, with significant impact on individuals and systems. In particular, concern 

about possible effects many years in the future (i.e. cancer and second generation 

effects), even if poorly supported by data or of little significance to any one individual, 

causes fear and initiated requests for monitoring. These considerations should be 

included in planning for response and communication post-event. 

As has been discussed in other modules today, identification of responsible individuals 

and even the source of a toxin may be challenging. This can be seen even with rapidonset 

toxins (e.g. Chicago cyanide contamination of over-the-counter analgesics is still 

an unsolved crime); identification of the culprit or extent of exposure following 

surreptitious use of a delayed-onset toxin will be much more difficult, leading to yet more 

fear and uncertainty. 





Slide 41 


Questions 


41 





Slide 42 


Supplemental Slides 


42 

Instructor Note: If time permits you may include following slides in your presentation. 





Slide 43 



Polybrominated Biphenyl (PBB) Exposure 

through Contaminated Food 

Michigan (1973) 

• Chemical plant packaged FireMaster 

flame retardant (PBB) and 

NutriMaster (MgO dairy cattle feed 

supplement) in similar brown paper 

bags due to a shortage of pre -printed 

bags. 

• Ten to twenty 50lb bags of PBB were 

included in a truckload of NutriMaster 

sent to a cattle feed mill during the 

summer of 1973. 

• PBB contaminated cattle feed was 

sold to dairy farms throughout the 

state 


43 

A chemical plant that manufactured both FireMaster flame retardant (containing 

polybrominated biphenyls (structure shown in graphic) and Nutrimaster (magnesium 

oxide feed supplement) mistakenly included 10-20 50 pound bags of the flame retardant 

in a shipment to a cattle feed mill in 1973. 

The mistake occurred because of a shortage of pre-printed bags. 

PBB contaminated cattle feed was sold to dairy farms throughout the state. 

A simple error in the distribution process led to this mass poisoning event. 





Slide 44 





• Weight loss, decreased milk 

production, and nonspecific illness 

noted among dairy herds in Fall 

1973, Spring 1974 

• After months of analysis, PBB 

detected in feed in April, 1974. 

• Quarantine of dairy herds and other 

farm animals started in May, 1974. 

• By 1975, 500 farms quarantined: 

– 30,000 cattle 

– 4500 swine 

– 1500 sheep, 

– 1.5 million chickens destroyed and 

buried. 


44 

Weight loss, decreased milk production, and nonspecific illness were noted among dairy 

herds in the fall of 1973 and spring of 1974. The cause was not known until PBB was 

detected in feed in April, 1974. 

Quarantine of dairy herds and other farm animals started in May, 1974. By 1975, 500 

farms quarantined: 30000 cattle, 4500 swine, 1500 sheep, and 1.5 million chickens were 

destroyed and buried. 









• Widespread, low level human exposure to PBB occurred 

throughout Michigan. E.g. 51 of 53 (96%) of random breast 

milk samples in 1976 had detectable levels. 

• Exposure most intense among dairy farm families, and 

persons obtaining dairy foods directly from quarantined 

farms. 

• High dose animal studies revealed PBB could cause 

multisystemic effects, including liver neoplasms 

• Between 1976 - 1979, state and federal agencies assembled 

a cohort of ≈ 4000 people, mainly farm families, to study 

long-term human health effects. 


45 

Widespread, low level human exposure to PBB occurred throughout Michigan. 

Practically all sampled human breast milk in 1976 had detectable levels. Exposure was 

most intense among dairy farm families, and persons obtaining dairy foods directly from 

quarantined farms. High dose animal studies revealed PBB could cause multisystemic 

effects, including liver neoplasms. 

Between 1976 and 1979, state and federal agencies assembled a cohort of ≈ 4000 

people, mainly farm families, to study long-term human health effects. 





Slide 46 

Similar to other organohalide compounds discussed in the last 1/3 of this module, PBB is 

highly lipophilic and extremely persistent. 

The apparent elimination half-life, measured in the blood, is approximately 10.8 years. 

The initial results reported on the cohort of exposed individuals (at about 4 years after 

exposure) did not identify any relationship between serum levels and symptoms; in fact 

the highest symptom prevalence occurred in subjects with lowest serum PBB. 

Because of concern about potential immunologic impact, lymphocyte count and function 

were also evaluated. No relationship was identified. 

An epidemiologic study reported in 1998 raised a question of carcinogenesis, but the 

study had many limitations. The findings have not been confirmed. 





Slide 47 





Module Six Summary 

Unlike the general concept of chemicals poisoning, in which the onset is rapid and the source 

identifiable, some toxins may have a delayed onset of symptoms. This could be beneficial to its 

use as a covert weapon from the perspective of a terrorist. Allowing time for victims to leave 

may seem like a “bad thing” to a terrorist, but in reality this complicates the epidemiology 

(figuring out the cause of the problem and source) and makes clinical management more 

difficult. More exposures may occur because there are no warning properties of exposure. In 

acute onset toxins, most people will escape when those around them start to get sick. But if 

nobody gets sick….nobody realizes they are being poisoned….and nobody escapes. 

Chemical agents with a delayed toxicity onset can be organized and separated based on 

route/scenario of exposure. Some are airborne (phosgene), food and waterborne (thallium, 

organomercurials, radionuclides/radioactive metals), and environmental/ biopersistent agents 

(dioxins, PCBs and PBBs). 

Choice of a toxin with delayed onset not only allows time for the perpetrator to escape and 

complicates diagnosis and response, but creates the potential for a large number of victims 

which may result in overwhelming the health care system with large numbers of patients with 

“medically unexplainable symptoms” presenting in dispersed fashion. This will contribute to 

creating chaos and social terror. The delayed onset of these agents may mimic some biological 

agents (anthrax, smallpox). 

Thallium has many qualities that allow it to be used as a terrorist weapon and has a long history 

of use as a homicidal toxin. The “classic triad” of gastrointestinal symptoms, paresthesias, and 

alopecia is obvious only if you know about it. Most physicians are not aware of this syndrome 

and will likely go looking in the wrong direction…..many other things cause painful neuropathy 

(e.g., diabetes, HIV) but none are as acute in onset as that from thallium (days). 

Organomercurials are examples of an agent used to raise fear and concern. It is widely believed 

to be extremely toxic, although the majority of us are exposed to small doses on a daily basis. It 

provides the opportunity to highlight the importance of physical state and chemical form in 

determining toxicity. While elemental mercury is of minimal toxicity in is liquid form, when 

inhaled following volatilization it can produce both irritant lung syndrome and neurotoxicity. 

Although low level exposure to a vapor over a long period can produce neurotoxicity without 

pulmonary abnormalities, this would not be a very effective terrorist weapon. Organic mercury 

compounds (those in which Hg is bound to a carbon backbone) are widely used in industry and 

science, and vary in toxicity from virtually none (as in organic mercury present in vaccines) to 

devastating, as is the case with dimethylmercury. Depending on the specific organic mercury 

compound, they can be absorbed by virtually every route, including dermal. 

Even less toxic compounds which are biopersistent and whose detection is delayed (such as 

the dioxins and other halogenated hydrocarbons) have enormous potential to cause fear and 

overwhelm health care resources 

Highly toxic substances whose onset of toxicity is delayed are currently readily available; these 

delayed effects can be used to affect large numbers of people before an event is discovered. 

The delay in onset of toxicity aids a would-be terrorist in avoidance of detection and escape 

while serving the purpose of creating uncertainty and panic. Due to the dramatic increase in 

terrorist activities both in internal strife and in international settings and a new willingness by 

terrorists in the 21st Century to use previously unthinkable means to meet their ends, we must 





prepare to limit access to highly toxic agents, ensure greater protections of food and water 

supplies, and more closely monitor toxic substances in industrial plants and in transport. Access 

to toxic agents must be stringently monitored and limited, both those with rapid onset and those 

that are delayed in onset of toxicity. Improving our public health and medical response/care 

system is critical to prevent sickness and save lives. 





Module Seven 

Radiation Emergencies - Administration Page 

The concept of terrorists using radiation as a weapon is extremely concerning. Ionizing or 

“nuclear” radiation has the clear potential to “terrify” the public as it is associated in the public 

mind with the destructive force of nuclear weapons, it is invisible and acutely undetectable to the 

senses, and is associated with the “dread of cancer”; with other effects not well understood by 

general public. Clinicians can play a vital role in minimizing fear and panic. 

Several potential scenarios involving the use of radiation by terrorists include the surreptitious 

placement of a radiation source, the stealth dispersal of radioactive material, an explosive 

radiation dispersal device (“dirty bomb”), a deliberate attack on a nuclear power plant, or the 

detonation of a nuclear weapon. 

Medical personnel may be called upon to care for patients who have been exposed to high 

levels of radiation or who have been contaminated with radioactive materials. Some of these 

patients may be gravely ill with radiation sickness or may have radiation burns, while others may 

have no radiological medical problems other than minor skin contamination. It is essential that 

medical personnel be able to recognize radiation injury and provide appropriate treatment. It is 

also essential that medical personnel understand that patients who are merely contaminated 

may be treated without risk of radiation injury to the medical staff, although contamination 

control measures may be prudent if the medical condition permits. 

Acute radiation syndrome is a constellation of signs and symptoms that develop after total body 

irradiation. The initial signs and symptoms of radiation illness are nonspecific, and could be 

misdiagnosed as a viral syndrome, or gastroenteritis. It is important in triage to attempt to 

ascertain the time interval between a person’s acute radiation exposure and the onset of 

gastrointestinal signs and symptoms. Individuals who become symptomatic in less than 4 hours, 

and certainly in less than 2 hours after exposure are likely to have absorbed a lethal dose of 

radiation and cannot be saved. In a mass casualty incident, they might have to be triaged to 

palliative care rather than intensive supportive care. 

Duration 

45 minutes 


This module presents the major potential scenarios involving the release of radiation by 

terrorists and reviews the basic fundamentals of radiation biology and concepts of exposure, 

contamination and containment. Decontamination and treatment strategies are presented for 

managing victims of radiation exposure. 


• Understand the concepts of radiation poisoning to assess and provide 

clinical care to patients who have been exposed to or contaminated 

with radioactive material. 






Resources 

• Describe five potential terrorist scenarios involving the use of 

radiation. 

• Describe the basic types of radiation. 

• Distinguish between radiation and radioactive contamination. 

• Recognize common types of radiological incidents and emergencies. 

• Describe the clinical signs of radiation exposure. 

• Understand the importance of treating significant medical and 

psychological problems in patients with radioactive contamination. 

• Explain basic radiological control methods. 









1. Andrews GA, Auxier JA, Lushbaugh CC. The Importance of Dosimetry to the 

Medical Management of Persons Exposed to High Levels of Radiation. In 

Personal Dosimetry for Radiation Accidents. Vienna : International Atomic 

Energy Agency; 1965. 

2. Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric 

oxygen therapy for late radiation tissue injury. Cochrane Database of 

Systematic Reviews 2005, Issue 3. Art. No.: CD005005. 

3. Cable News Network (CNN). Sentence in Radiation Poison Case. 

CNN.com/World, October 2, 2003. Accessed Dec 2008 from: 

http://www.cnn.com/2003/WORLD/asiapcf/east/10/02/china.radiation/ 

4. Centers for Disease Control and Prevention. Acute Radiation Syndrome: 

Physician Fact Sheet. CDC Emergency Preparedness and Response. 


http://www.bt.cdc.gov/radiation/arsphysicianfactsheet.asp 

5. Centers for Disease Control and Prevention. Cutaneous Radiation Injury: 

Fact Sheet for Physicians. CDC: Emergency Preparedness and Response. 


http://www.bt.cdc.gov/radiation/criphysicianfactsheet.asp 

6. Centers for Disease Control and Prevention. Emergency Preparedness and 

Response. Fact Sheet: Prussian Blue. Accessed Dec 2008 from: 

http://www.bt.cdc.gov/radiation/prussianblue.asp 





7. Centers for Disease Control and Prevention. Emergency Preparedness and 

Response: Radiation Emergencies. Accessed Dec 2008 from: 

http://www.bt.cdc.gov/radiation/ 

8. Centers for Disease Control and Prevention. Possible Health Effects of 

Radiation Exposure on Unborn Babies. CDC: Emergency Preparedness and 

Response. Accessed Dec 2008 from: 

http://www.bt.cdc.gov/radiation/prenatal.asp 

9. Centers for Disease Control and Prevention. Radioisotope Brief: Iodine-131. 


http://www.bt.cdc.gov/radiation/isotopes/pdf/iodine.pdf 

10. Centers for Disease Control and Prevention. Radioisotope Brief: Cesium-137. 


http://www.bt.cdc.gov/radiation/isotopes/cesium.asp 

11. Clinical Response of Normal Tissues in Radiobiology for the Radiologist. Hall 

EJ, Giaccia AJ (eds). Lippincott Williams & Wilkins, Philadelphia PA, 6th 

edition, 2006. 

12. Cutaneous Radiation Syndrome. Radiation Event Medical Management: 

Guidance on Diagnosis & Treatment for Health Care Providers. Accessed 

Dec 2008 from: http://www.remm.nlm.gov/cutaneoussyndrome.htm 

13. Ferguson CD, Kazi T, Perera J. Commercial radioactive sources: surveying 

the security risks. Occasional Paper No. 11, Center for Nonproliferation 

Studies, Monterey Institute of International Studies, CA; 2003. 

14. Holt M, Andrews A. Nuclear Power Plant Security and Vulnerabilities. CRS 

Report for Congress, Congressional Research Service; 2008. Accessed Dec 

2008 from: http://www.fas.org/sgp/crs/homesec/RL34331.pdf 

15. International Atomic Energy Agency. “The Radiological Accident in Goiania.” 

IAEA, STI/PUB/815 (ISBN 92-0-129088-8);Vienna, 1988. 

16. International Atomic Energy Agency. Goiânia’s Legacy Two Decades On: 

Accident led to review of international safety standards for radiation; March 7 


http://www.iaea.org/NewsCenter/News/2008/goiania.html 

17. Ionizing Radiation During Pregnancy. Exposure to radiation and physical 

agents during pregnancy. Accessed Dec 2008 from: 

www.perinatology.com/exposures/Physical/Xray.htm 

18. Isotopes for Medicine and the Life Sciences. Adelstein SJ, Manning FJ (eds) 

Instititute of Medicine. National Academy Press, Washington D.C.; 1995. 

19. Jordan M, Finn P. “Radioactive Poison Killed Ex-Spy”. Wasingtonpost.com; 

November 25, 2006. Accessed Dec 2008 from: 

http://www.washingtonpost.com/wpdyn/content/article/2006/11/24/AR2006112400410.html 

20. Kuniak M, Azizova T, Day R, et al. The radiation injury severity classification 

system: an early injury assessment tool for the frontline healthcare provider. 

Br J Radiol 2008;81:232-243. 

21. Managing Radiation Emergencies: Guidance for Hospital Medical 

Management. REAC/TS Guidance for Radiation Accident Management – 





Decontamination. Accessed Dec 2008 from: 

http://orise.orau.gov/reacts/guide/emergency.htm#Decontamination 

22. McFee R. “Exclusive: the death of Litvinenko – two years later and what have 

we learned” Family Security Matters 2008. Accessed Dec 2008 from: 

www.familysecuritymatters.org/publications/id.1969/pub_detail.asp 

23. Mettler FA Jr, Voelz GL. Major radiation exposure – what to expect, how to 

respond. N Engl J Med 2002;346:1554-1561. 

24. Nuclear Energy Advisory Committee. Nuclear Energy: Policies and 

Technology for the 21st Century. Department of Energy, November 2008. 

25. Ortiz P, Friedrich V, Wheately J, Oresugun M. Lost and found dangers: 

orphan radiation sources raise global concerns. IAEA Bulletin 1999; 413:18- 

21. 

26. Osborn A. “Now traces of polonium 210 are found in Russian businessman’s 

flat”. The Independent; December 10, 2006. Accessed Dec 2008 from: 

http://www.independent.co.uk/news/world/europe/now-traces-of-polonium- 

210-are-found-in-russian-businessmans-flat-427862.html 

27. Parker DD, Parker JC. Estimating radiation dose from time to emesis and 

lymphocyte depletion. Health Physics. The Radiation Safety Journal 

2007;93(6):701-704. 

28. Pastel RH. Fear of radiation in U.S. military medical personnel. Military Med 


http://findarticles.com/p/articles/mi_qa3912/is_200112/ai_n9008782 

29. Patterson AJ. Ushering in the era of nuclear terrorism.[editorial] Crit Care 

Med 2007;35(3):953-954. 

30. Public Broadcasting Service. Frontline. Nuclear Reaction: Why do Americans 

Fear Nuclear Power Accessed Dec 2008 from: 

http://www.pbs.org/wgbh/pages/frontline/shows/reaction/interact/facts.html 

31. Radiation Event Medical Management: Dose Estimator (Biodosimetry Tools). 

National Library of Medicine. Accessed Dec 2008 from: 

http://www.remm.nlm.gov/ars_wbd.htm#vomit 

32. Radiation Event Medical Management: Explaining Biodosimetry. National 

Library of Medicine. Accessed Dec 2008 from: 

http://www.remm.nlm.gov/explainbiodosimetry.htm 

33. Radiological Terrorism Tutorial: Iridium-192. Nuclear Threat Initiative. 


http://www.nti.org/h_learnmore/radtutorial/iridium192.html 

34. Rubin GJ, Page L, Morgan O, et al. Public information needs after the 

poisoning of Alexander Litvinenko with polonium-210 in London: cross 

sectional telephone survey and qualitative analysis. BMJ 2007;335:1143. 

35. Shope TB. Radiation-induced skin injuries from fluoroscopy. FDA: Center for 

Devices and Radiological Health. Accessed Dec 2008 from: 

http://www.fda.gov/cdrh/RSNAii.html 

36. United States Department of Health and Human Services. Radiation Event 

Medical Management (REMM): Guidance on Diagnosis & Treatment. 





Dictionary of Radiological Terms. Accessed Dec 2008 from: 

http://www.remm.nlm.gov/dictionary.htm 

37. United States Department of Homeland Security. Radiation Portal Monitors. 

Homeland Security TechNote; System Assessment and Validation for 

Emergency Responders (SAVER); April 2006. 

38. United States Department of Labor: OSHA. Safety and Health Topics: Non- 

Ionizing Radiation. Accessed Dec 2008 from: 

http://www.osha.gov/SLTC/radiation_nonionizing/index.html 

39. United States Department of Labor: Occupational Safety & Health 

Administration (OSHA). Safety and Health Topics: Ionizing Radiation. 

Accessed Dec 2008 from: http://www.osha.gov/SLTC/radiationionizing/ 

40. United States Nuclear Regulatory Commission. Fact Sheet of Dirty Bombs. 

Accessed Dec 2008 from: http://www.nrc.gov/reading-rm/doc-collections/factsheets/dirty-bombs.html 

41. United Nations. Chernobyl’s Legacy: Health, Environmental and Socio- 

Economic Impacts and Recommendations to the Governments of Belarus, 

the Russian Federation and Ukraine. The Chernobyl Forum: 2003-2005; 2nd 

edition, rev. 

42. United States Environmental Protection Agency. Radiation Protection. 

Accessed Dec 2008 from: http://www.epa.gov/rpdweb00/ 

43. Waselenka JK, MacVittie TJ, Blakely WF, Pesik N, Wiley AL, Dickerson WE, 

Tsu H, Confer DL, Coleman N, Seed T. Medical Management of the Acute 

Radiation Syndrome: Recommendations of the Strategic National Stockpile 

Radiation Working Group, Annals of Internal Medicine 2004; 140:1037-1051. 

44. World Health Organization. Health Effects of the Chernobyl Accident and 

Special Health Care Programs. Bennett B, Repacholi M, Carr Zhanat (eds.); 

Geneva, 2006. 

45. Yard, CR. Lost radiation sources: Raising public awareness about the 

hazards associated with industrial and medical radiography sources. J 

Environ Health 1996;58. 























Module Seven 

Icon Map 






instruction 





Slide 1 

This module presents the major potential scenarios involving the release of radiation by 

terrorists and reviews the basic fundamentals of radiation biology and concepts of 

exposure, contamination and containment. Decontamination and treatment strategies 

are presented for managing victims of radiation exposure. 

While the science dealing with generation of energy sufficient to disrupt elements 

(ionizing radiation)and the release of radiation from radioactive isotopes (high-energy 

forms of some elements) seems distant from medical toxicology (the science of human 

poisoning), there are many areas of overlap or similarity. 

The principles of dose response, specificity of effect (toxidromes), and the importance of 

supportive care with appropriate use of antidotes during treatment are exactly the same 

in the evaluation of a terrorist event involving radiation or the typical industrial chemical 

release. In addition, the principles of risk communication are very important (perhaps of 

primary importance) in most potential radiation terrorist events. 





Slide 2 

The objectives for this presentation include: 

- Identify the settings where radioactive materials may be used or obtained for terrorist 

attacks 

- Describe five potential major terrorist scenarios involving radiation 

- Review key concepts including the clinical effects of the various types of radiation, 

such as alpha particles and gamma rays. Other key concepts include differentiation 

between radiation and radioactive materials, radiation contamination and incorporation, 

and how the human body manifests evidence of significant radiation poisoning. 

- Describe clinical response strategies including personal protection, decontamination, 

and antidotal therapy 

The most important concept to remember is that: 

1. we are all exposed to ionizing radiation daily 

2. exposure to ionizing radiation may cause injury in sufficient dose 

3. exposure to ionizing radiation does not make a person “radioactive” 

4. radioactive material on the skin is external contamination, while inhaled, ingested, or 

penetrating injuries with radioactive particles marks internal contamination or 

incorporation; assessment and treatment should address these differences and prevent 

any further internal contamination 





Slide 3 

Nuclear (radioactive) materials are found in a number of locations, including: 

Irradiation facilities, used for treating food products and other materials 

Nuclear reactors used for generating power 

Materials testing devices such as those used to test metal frame (bridge) or pipeline 

integrity 

X-ray devices in healthcare settings 

isotope production facilities for use in many applications including in medicine/research. 

Other locations such as in-transit or junkyards or abandoned or transported material 

used in pre-regulatory days (pre-1960s) are in sites that we may not know about. 





Slide 4 

There are an estimated 2 million devices in the USA contain licensed radioactive 

sources, but there is no comprehensive national inventory. 

Companies have reported losing track of almost 1700 sources since 1998. More than 

half have yet to be found. While some sources, such as those for irradiating food, are 

meters in size, others, such as those in industrial radiography cameras, are small, 

measuring only millimeters in size. 

In particular, some of these sources could become detached from their connections and 

be lost on a worksite or picked up by someone thinking it was a random piece of metal, 

leading to significant exposure, severe local tissue injury, and in some cases, death. 





Slide 5 

We will briefly describe five major potential terrorist scenarios involving the use of 

radiation. These scenarios include the: 

Surreptitious placement of a radiation source which would radiate those in proximity. 

Stealth dispersal of radioactive material which would spread exposure over a larger area 

Explosive radiation dispersal (“dirty bomb”) which, of course, would not be subtle – if 

radiation monitoring were conducted at every explosive event. 

Attack on a nuclear power plant, which would potentially release a large number of 

fission products over a widespread area. 

Detonation of a nuclear weapon, which would make for a very bad day. While much of 

the impact of such a release are outside the scope of toxicology, some of the 

management issues that incorporate dose and fallout (downwind drift of radioactive 

material from an explosive release) will be discussed. 





Slide 6 

How would you know if someone placed a radioactive source in your vicinity 

As shown, some of these sources are very small – such as the source (usually Iridium- 

192) in the tips of these pigtail catheters, housed in shielded containers (known as 

“pigs”) shown at the top of the slide. 

These pigtails can become disconnected. They are unmarked and have been pocketed 

or carried about the worksite – resulting in severe local radiation tissue injury, and 

systemic poisoning, including death. 

Yet radiation is the easiest to detect of all of the terrorist weapons – if it is sought using a 

radiation detector. 

Of course, all agents (biologic, chemical, radiologic/nuclear) can also be identified by the 

toxidrome displayed once people become ill, but that can be non-specific and also takes time to 

develop. 





Slide 7 

In this case, a nuclear medicine expert placed some illegally obtained iridium-192 above 

the ceiling tiles of his partner’s office, with whom he had had a dispute. Within days, the 

partner developed typical acute radiation sickness, as did seventy-four other hospital 

employees, before the surreptious placement of these sources was identified. Note the 

tiny size of iridium disks (2mm diameter) in the graphic. The perpetrator was arrested 

and sentenced to death. 

Slide 8 





Turning to an example of the next potential scenario, the Goiânia Brazil tragedy is 

probably the best-known example of surreptitious (though unintentional) dispersal of a 

radioactive source in a community, although there have been other cases over the 

years. 

In 1987, a radiotherapy device was found in an abandoned clinic by a few young men. 

They broke it open and found a blue glowing powder, which, unknown to them, was 

Cesium-137. These individuals sold it to a junkyard dealer. He broke it fully open and 

brought the glowing object into his home, and gave some of the powder to friends and 

family. The young daughter of the dealer rubbed some of this glowing powder onto her 

face. Once several of them started to get sick, the connection to the source was 

suspected, and a large public health response began. 

Note that it took nearly 2 weeks from the time of initial Cesium dispersal to discovery of 

the cause of illness in the affected individuals. 

Luminescence, or “blue glow” from the powder represents the presence of Tschenkov 

radiation. This occurs when high energy Beta particles released by the Cesium 

temporarily ionize water vapor molecules in the air. Some energy is released as visible 

blue light in the process. 

Lessons drawn from this accident in Brazil are still helping shape actions on radiation 

safety and security decades later. It was the worst accident involving a small radioactive 

source that the world has seen. 





Slide 9 

There was widespread concern about potential environmental contamination because of 

the delay in discovery of radiation poisoning, disruption of the shielding of the device, 

and potential run-off from the area. In addition to environmental surveys, ~112,000 

people were surveyed for contamination by having them walk through radiation portal 

monitor in a soccer stadium. More detailed screening was done for those demonstrating 

contamination. 

Note that in almost half the contamination incidents (only 0.2% of those screened), 

contamination was confined to clothing. 46 people received chelation therapy with 

Prussian Blue (to bind cesium in the bowel), and 14 suffered bone marrow failure, a 

classic sign of radiation poisoning. 8 of these received GM-CSF. 4 died. 

One of the people who died included the daughter of the junk yard dealer. 





Slide 10 

The next scenario involves incorporating a small amount of radioactive material (“dirty”) 

to a conventional explosive. This allows the dispersion of radiation over a fairly large 

area (typically in the range of thousands of square yards). Given the ready detectability 

of radiation, if monitoring is performed, few individuals are likely to absorb a lethal dose 

before they can evacuate the area. Some may be impaled with contaminated shrapnel 

or inhale radioactive dust and develop radiation sickness (poisoning), but human 

casualties are likely to be low. 

A “dirty bomb” is one type of a “radiological dispersal device” (RDD) that combines a 

conventional explosive, such as dynamite, with radioactive material. Most RDDs would 

not release enough radiation to kill people or cause severe illness. The energy of a dirty 

bomb explosion is derived from the amount of conventional explosive used and is much, 

much less than that of a nuclear bomb; the energy of a nuclear bomb is derived from 

fission, releasing a number of fission products that are not present with a dirty bomb. 

There is no radioactive iodine generated by a dirty bomb – and thus no role for the often 

mischaracterized “anti-radiation pill” potassium iodide. 

Depending on the scenario, an RDD explosion could create fear and panic, contaminate 

property, and require potentially costly cleanup. A dirty bomb is not a “Weapon of Mass 

Destruction” but a “Weapon of Mass Disruption,” where contamination and anxiety are 

the terrorists’ major objectives. 





Slide 11 

A deliberate attack on a nuclear power plant is a possibility of grave concern, particularly 

after September 11 2001, as questions about the ability of containment or control room 

structures to withstand an airliner crash were raised. 





Slide 12 

On 26 April 1986, the most serious accident in the history of the nuclear industry 

occurred in the Chernobyl nuclear power plant in the former Ukrainian Republic of the 

Soviet Union. Explosions damaged the reactor vessel and the subsequent fire dispersed 

large amounts of radioactive materials into the environment (estimated at 400 times the 

fallout of the Hiroshima atomic bomb). Iodine and cesium were the major radionuclides 

released. Two people died in the initial steam explosion, but most deaths from the 

accident were attributed to radioactive fallout. Initially there were 134 victims of acute 

radiation poisoning, but several thousand cancer cases from radiation exposure 

(primarily thyroid cancer in young children) have occurred; more cancer cases and 

deaths are expected over the next few decades. Psychological effects have also been 

documented among the exposed population, attributed to both poor communication 

about risk and the social disruption in the region.The greatest deposition of radionuclides 

occurred over large areas of the Soviet Union surrounding the reactor in what are now 

the countries of Belarus (60% of fallout), the Russian Federation and Ukraine. Initial 

identification of the event actually came from a Swedish nuclear power plant radiation 

alarm 1000 miles away that detected the drifting radioactive fallout “cloud” from the 

event. Initial evacuation and potassium iodide treatment of downwind residents was also 

markedly delayed. 





Slide 13 

Radiation is energy in the form of electromagnetic waves or subatomic particles. 

Radiation is usually thought of as either rapidly propagating waves or individual particles 

emitted by the nucleus (or other component) of an atom as it changes from a higher 

energy state to a lower energy state. 

Radiation can be classified as ionizing or non-ionizing, depending on its effect on atomic 

matter. "Radiation" usually refers to ionizing radiation, which is radiation that has 

sufficient energy to ionize atoms or molecules; non-ionizing radiation does not. 





Slide 14 

Ionizing radiation has sufficient energy to strip electrons off of atoms. In biological 

systems this raises the potential for both acute and chronic effects. 

People are very concerned about ionizing radiation in large part related to its association 

with nuclear bombs and a limited understanding of what ionizing radiation can and 

cannot do. Furthermore, radiation is undetectable by our innate senses, though readily 

detected, unlike biological or chemical agents, with widely available equipment (e.g. 

Geiger-Mueller counter). 

The figure shows the electromagnetic spectrum, which depicts how radiation is broken 

into types according to the frequency (or wavelength) of the wave. These types, in order 

of increasing frequency (or decreasing wavelength) and increasing danger, include radio 

waves, microwaves, infrared radiation, visible light, ultraviolet radiation, X-rays and 

gamma rays. Of these, radio waves have the longest wavelengths and Gamma rays 

have the shortest. The visible spectrum includes the frequencies sensed by the eye and 

depicted by the color spectrum in the figure. 





Slide 15 

Non-ionizing radiation refers to any type of radiation that does not carry enough energy 

to ionize atoms or molecules. These are represented in the electromagnetic spectrum by 

waves of longer wavelength (lower frequency). 

Examples include UV (ultraviolet) light, radio waves, microwaves, visible light. This does 

not mean that these forms of radiation have no physical effects, but rather that they don’t 

produce their physical effects (e.g. activating cells in the retina to transmit signals 

interpreted by the brain as sight for the visible light spectrum) via the highly injurious 

method of ionization. 





Slide 16 

In order to understand radiation, we need to briefly review the structure of matter. An 

atom consists of a nucleus, made up of protons (positively charged) and neutrons (no 

charge, neutral), surrounded by a cloud of rapidly moving electrons (negatively charged). 

Electrons are tiny compared to protons and neutrons, which are approximately the same 

size. 

The four basic types of ionizing radiation include: 

alpha particles are essentially helium nuclei (2 protons and 2 neutrons), ejected from the 

nucleus of a larger atom and moving with high energy. Following an alpha emission, the 

atom transforms from one element into another (since an element is defined by its 

number of protons, the atomic number). 

A beta particle is an electron that is ejected from the electron cloud around the nucleus. 

Gamma radiation is not particulate, but rather electromagnetic rays that are emitted from 

the nucleus. X-rays are similar to gamma rays, but have an origin outside the nucleus. 

Neutrons are uncharged particles ejected from the nucleus. 

Beta release, gamma ray, X-ray, or neutron release do not change the atom into another 

element. 





Slide 17 

One way to differentiate the potential effects of external radiation is by their ability to 

penetrate the body. 

Alpha particles do not penetrate even the dead layer of skin and can be stopped by a 

thin layer of paper or clothing. However, if one ingests or inhales an alpha emitting 

radioactive material the radiation can cause damage to the tissue it is next to, such as 

the lung cells. 

Beta particles are only moderately penetrating, though energy varies by the element. 

Some beta radiation can penetrate human skin to the layer where new skin cells are 

produced. If beta emitting contaminants remain on the skin for a prolonged period of 

time, they may cause skin injury resembling sunburn. They may also be harmful if 

deposited internally. 

Gamma rays and x-rays are able to travel into or through human tissue (thus the use of 

x-rays in medical imaging). Lead is needed to stop these. 

Neutrons also penetrate most materials. They are able to travel many feet in concrete, 

yet may be stopped by large amounts of water. Neutrons are not likely to be 

encountered in dirty bomb events, but would be seen after a nuclear bomb detonation. 





Slide 18 

It is important to differentiate between radiation and radioactive material. Radiation is the 

energy released from a source and is in the form of waves or particles (i.e alpha, beta, 

gamma, or x-rays). 

Radioactive material is the substance that emits ionizing radiation. A radioisotope is a 

radioactive material that emits radiation. 

Differentiate that radiation sources may either be intrinsically radioactive and continually 

emit radiation (as with radioisotopes), or may be able to generate radiation on demand 

by an electric current releasing electrons (as from the tungsten filament in a hospital X- 

ray machine). 





Slide 19 

A person may be exposed to radiation at a distance, particularly with X-rays and gamma 

rays. When that happens, the person has been irradiated and can suffer serious 

sequelae if the radiation dose absorbed by the body is sufficient. 

However, that person, if tested with a Geiger counter would not be emitting radiation; 

that is, the person would not be radioactive. 

Exposure to radiation equals irradiation. There is no residual radioactivity once the 

person leaves the exposure. 

This is different than having radioactive material on or in the body. This is contamination 

and is discussed next. 





To become contaminated, radioactive material must get on a person’s skin or clothing, 

or inside the body. For example, people could become contaminated if they were near 

an explosion such as a ‘dirty bomb’. 

Radioactive material sitting on the clothes or skin is called external contamination. 

Simply removing the clothing and washing the hair and skin will remove the majority of 

the contamination. 

Radioactive material inside the body is called internal contamination, and is more difficult 

to remove. If the radioisotope is taken up by tissue, it is said to be incorporated into the 

body. Medical therapy may be required to help clear this material. 

These patients are themselves giving off radiation and require more caution than those 

who are simply irradiated. 

Washing the skin with a mild soap is generally recommended to decontaminate patients 

with external contamination. 





Slide 21 

There are commonly used radiation terms to describe the energy released and its effect 

on the body. These terms and their derivation is somewhat complex; memorization is not 

required. Manhyy of the terms are based on important person in radiation science 

history, such as Marie Curie (who coined the term radioactivity and discovered radium 

and polonium). A general understanding is fine for most clinical needs. 

The activity of an isotope is the number of disintegrations that occur per second. A 

disintegration is what happens in the nucleus, causing the release of radiation. The more 

disintegrations per second, the more radioactive (all other things being equal). The units 

are the Curie or Becquerel. 

The amount of radiation deposited onto or into the person, or the dose, is measured in 

rads or Grays. But more importantly is the amount of biological damage done by that 

amound of absorbed radiation. This is measured in rem or Seivert, and is basically the 

deposited dose multiplied by a factor that differs based on the type of radiation (ie., 

alpha vs beta vs gamma, etc). 





Slide 22 

This slide shows some common examples of ionizing radiation exposures, including 

background levels coming from the sun, releases from rocks, food, and water that are 

experienced by everyone. Each year the average person is exposed to a dose of 360 

mrem of ionizing radiation (or about 1mrem/day). These amounts on a continuous basis 

or with single exposures, such as to an X-ray, can be compared with the amounts 

needed for a single exposure to cause acute radiation symptoms. 





Slide 23 

The injuries that can be caused by or associated with exposure to large amounts of 

radiation or radioactive materials are listed here. Acute radiation syndrome is the most 

consequential life threat, though each of the others results in significant physical and/or 

psychological concerns. Acute radiation syndrome generally follows whole body high 

dose irradiation. Localized radiation injuries are most commonly seen with a small 

gamma (or potentially beta) source in sustained contact with the body (such as being 

carried in a pocket). We will describe the increased sensitivity of the developing fetus to 

radiation in the setting of maternal exposure. . 

Contamination – and the importance of limiting internal contamination in the setting of 

radiological materials or a “dirty bomb” explosion will be covered. Of course, significant 

trauma from shrapnel in this situation should always be considered; missed injuries will 

be of more problematic than a short delay in assessment of radiation injury. 





Slide 24 

Many people have unrealistic perceptions of what radiation can do. This is related to our 

innate fear of what we do not understand – and are unable to see, as well as the media 

portrayal of radiation effects (as in Godzilla movies and comic books). Although the 

blast of a dirty bomb (or nuclear bomb) may kill, radiation itself does not cause 

immediate death or immediate burns or wounds. Instead, radiation exposure sets in 

motion a series of events in various body tissues that may ultimately lead to death in 

hours to days to years following exposure. These organ system effects will be described 

in the next several slides. 

While radiation exposure and/or contamination with radioactive material should be 

addressed in the early management of a patient, there is absolutely no risk to healthcare 

providers who are treating a patient who has been irradiated. A few simple procedures 

reduce healthcare worker exposure when caring for contaminated patients. Treat the 

patient first! 





Slide 25 

Radiation sickness, known as acute radiation syndrome (ARS), is a serious illness that 

occurs when the entire body (or most of it) receives a high dose of radiation, usually over 

a short period of time. ARS generally requires a whole body exposure to a type of 

radiation that passes the skin, such as gamma; or is delivered directly to the entire body, 

as with inhalation or ingestion of a large quantity of alpha particles. 

Radiation sickness, known as acute radiation syndrome (ARS), is a serious illness 

resulting from a total body dose of radiation over a short period of time. As examples, 

many survivors of the Hiroshima and Nagasaki atomic bombs in the 1940s and many of 

the firefighters who first responded after the Chernobyl Nuclear Power Plant accident in 

1986 became ill with ARS. 





Slide 26 

This chart shows the time course of ARS. The higher the dose, the shorter the time to 

symptom onset and the more severe the symptoms. Radiation symptoms follow a typical 

pattern (toxidrome). Typically, the first symptoms of ARS are nausea, vomiting, and 

diarrhea. The delay to onset is very important in predicting the dose. Symptom onsets < 

1 hour after exposure indicates a large radiation dose. Lower doses are associated with 

delays up to 48 hours. These symptoms will last for hours up to several days, and may 

come and go. Many of the initial signs and symptoms of radiation illness are 

nonspecific, and could be misdiagnosed as a viral syndrome, or gastroenteritis. The 

person may improve (particularly with supportive treatment) during what is termed the 

latent stage, after which he or she may become sick again with fatigue, fever from 

infection due to bone marrow toxicity (which also causes thrombocytopenia), recurrent 

gastrointestinal symptoms, and even seizures and coma in very high dose exposures. 

This seriously ill stage may last from a few hours up to several months with lower doses. 

Recovery depends on the dose and can be improved with advanced medical care. 





Slide 27 

Dosimetry is a method to gauge the severity of radiation exposure. Based on the specific 

syndrome that develops, the clinician and health physicist can determine the dose range 

to which a patient was exposed. In general, the higher the dose, the greater the severity 

of early effects and the greater the possibility of life threatening effects. Each of these 

syndromes represents an increasing exposure to radiation and carries a greater risk of 

adverse or fatal outcomes. We will discuss a few of them in more detail. 

1. Subclinical – while tissue damage may occur, no overt symptoms are expected and the body 

should be able to repair damage that has been done. 

2. Hematopoietic syndrome - characterized by bone marrow dysfunction with decreased 

lymphocyte, polymorphonuclear (PMN) white blood cells, and platelets, resulting in immunodeficiency, 

increased infectious complications, bleeding, anemia, and impaired wound healing. 

3. Cutaneous (Skin) syndrome - can occur with other syndromes; characterized by loss of 

epidermis (and possibly dermis) with "radiation burns." 

4. Gastrointestinal syndrome - characterized by loss of cells lining intestinal crypts and loss of 

mucosal barrier, with alterations in intestinal motility, fluid and electrolyte loss with vomiting and 

diarrhea, loss of normal intestinal bacteria, sepsis, and damage to the intestinal microcirculation, 

along with the hematopoietic syndrome. 

5. Cerebrovascular/Central Nervous System (CNS) syndrome - primarily associated with effects 

on the vasculature and resultant fluid shifts. Signs and symptoms include vomiting and diarrhea 

within minutes of exposure, confusion, disorientation, cerebral edema, hypotension, and 

hyperpyrexia. Requires massive exposure and is fatal in short time. 





Slide 28 

The hematopoietic syndrome (Bone marrow syndrome) will usually predominate with a 

dose between 1 and 5 Gy (100 – 500 rads) though mild symptoms may occur as low as 

0.3 Gy or 30 rads. Irradiation of the bone marrow results in a fall in lymphocytes, 

although some of the early fall in lymphocyte count (the first 2 days) is related to 

migration of lymphocytes out of the bloodstream in response to tissue injury. The degree 

and rate of fall serve as markers for the extent of exposure. Serial measurement of the 

lymphocyte count can be used prognostically. The survival rate of patients with this 

syndrome decreases with increasing dose. The primary cause of death is infection (no 

white blood cells) and hemorrhage (no platelets). 





Slide 29 

The clinical syndromes associated with a predominance of early onset of vomiting 

(gastrointestinal or GI syndrome) or early confusion, seizures or coma (central nervous 

system or CNS syndrome) indicate larger radiation doses and suggest a poor prognosis. 

Exposure above 6 Gray makes survival unlikely; this is approximately the same dose 

that causes the GI syndrome. 

Patients with early onset nausea and vomiting may die within the week of hemorrhagic diarrhea, 

or may survive to die within several weeks of bone marrow failure- related infection. 





Slide 30 

The diagnosis of Acute Radiation Syndrome requires a history of possible radiation 

exposure, information about the onset of early symptoms (nausea and vomiting) and 

serial complete blood counts (CBC) looking at the absolute lymphocyte count. 

In the setting of an earlier occult radiation exposure, the diagnosis is more difficult. 

However, similar to the situation described with heavy metal poisoning in the Delayed 

Onset Toxin Module, a history of preceding gastrointestinal symptoms should be sought 

in patients who present with skin changes, hair loss, or patterns of blood cell line 

deficiencies that may suggest radiation as a potential cause. 

The onset time of signs and symptoms (in particular vomiting and diarrhea) following 

exposure correlates with the severity of exposure (more rapid onset equals larger 

radiation dose) and with the prognosis (more rapid onset equals worse outcome). 

The CBC is an assessment of the white blood cell (WBC), red blood cell, and platelet 

count. The diff, or differential count, is a slightly advanced analysis that looks at the 

types of white blood cells present. The WBC type of most importance is the lymphocyte 

(other types of WBCs are the neutrophils, monocytes, and eosinophils – which are not 

as sensitive to radiation effects as are the lymphocytes). Lymphocytes will drop quickly, 

followed by neutrophils, platelets, then red blood cells. 





Slide 31 

There are several algorithms that can be used to guide management and treatment 

decisions based on likely radiation dose received. One example is shown here where 

time to onset of vomiting is correlated with radiation dose. However, note that not all 

people will vomit, particularly at lower doses. In these situations it is helpful to have 

additional measurements, such as the lymphocyte depletion rate shown on the next 

slide. 

The need for early specialized care is to optimize chances for survival, which will entail 

strict attention to fluid and electrolyte balance, early operative care if indicated, 

preparation for neutropenia and use of reverse isolation procedures and specialized 

medications to increase bone marrow response (cytokines). The National Library of 

Medicine site has an interactive algorithm that is very useful. 





Slide 32 

The Andrews nomogram depicts early lymphocyte depletion following radiation exposure 

and can also be used to estimate dose (exposure to radiation). The lymphocyte count is 

derived from the complete blood count mentioned in a prior slide. 

The left axis is the lymphocyte count, and the bottom axis is the time since exposure. 

The green lines represent dose estimates which relates on the right to prognosis. The 

more rapid the lymphocyte fall (depletion), the higher the likely radiation dose; and the 

more severe the ensuing clinical course. 

A fall of the lymphocyte count below 1000 cells/milliliter of blood within 24 hours after 

exposure suggests a dose over 6 Gy and a very severe course, while a drop below 1000 

cells/ml within 12 hours may indicate a lethal exposure of over 8 Gy range. . 





Slide 33 

Localized radiation injury occurs when one part of the body receives a high dose of 

radiation. It can accompany the acute radiation syndrome (ARS) or occur in isolation. As 

with all radiation exposure, diagnosis is difficult without a good history of exposure. The 

cables (shown previously) contain radiation sources for use in a number of devices, such 

as assessing structural integrity of a weld. 

Inadvertent pocketing of items such as these can lead to severe local injury. 





Slide 34 

Localized radiation injury can also occur with therapeutic radiation for cancer treatment, 

although this is minimized by fractionated treatment and the use of multiple radiation 

“windows” and shielding. 

Findings are related to dose and generally follow a more severe course as the dose 

increases. For example 300 rads or 0.3 Gy will result in localized hair loss after a couple 

weeks, while doses above 1000 rads or 1 Gy will damage deeper skin structures, 

leading to tissue loss, and the possibility of poor wound healing. . 

Lesions may not appear for days or weeks, particularly with relatively low doses. 

The procedures used in radiation therapy units include targeting a tumor via multiple 

angles (windows), delivering the total dose over a period of daily treatments over weeks 

(fractional), and shielding uninvolved areas of the body. 





Slide 35 

In the absence of a history of exposure to a gamma source (such as the iridium-192 

containing radiography sources shown), the picture on the left could be of a wound from 

a variety of causes (including a traumatic injury, insect bite, or bacterial or fungal 

infection). This small wound, shown on the left, with significant surrounding redness 

(erythema) and swelling (edema) eventually became a significant ulceration (shown on 

the right). 

Radiation experts can use the eventual amount of tissue injury to calculate an 

approximate radiation dose (retrospective dosimetry). Alternatively, a known time of 

exposure to a known source can be used to develop a prediction of the likely extent of 

injury for prospective wound and surgical planning purposes. 





Slide 36 

Treatment for local radiation injury includes providing for the patients comfort with 

adequate pain control. They should avoid nicotine, which reduces blood flow to the skin. 

It is critical to prevent or rapidly treat infections that develop. Surgery to debride 

devitalized/dead tissue will help prevent infection, but the remaining tissue heals slowly 

and poorly. Hyperbaric oxygen therapy may have a role in improving blood vessel 

migration into this damaged tissue.The image shows the chronic wound that can follow 

localized radiation injuries. 

Erythema and dry desquamation can be treated symptomatically. Lotions or sprays 

containing hydrocortisone can be used to relieve the symptoms associated with severe 

erythema accompanied by edema. To treat moist desquamation, daily dressings and 

bathing of the affected skin in antiseptic solutions is helpful. Antibiotic creams can also 

be used. 

For ulceration, moist dressings and daily cleansing is recommended. Systemic 

antibiotics should be utilized for verified secondary infection. Surgical debridement can 

be problematic because of the poor vascularization and integrity of the surrounding 

tissue. Hyperbaric oxygen treatment has been demonstrated to improve new blood 

vessel growth and stem cell recruitment to ischemic tissue. It should be considered prior 

to and after surgical interventions. Opioid analgesics may be necessary for prolonged 

periods as this chronic wound heals.. 

The image depicts an individual with an estimated >20 Gy exposure from repeated 

fluoroscopy exposures to X-rays during a complicated series of angiography procedures 

on one day. Some erythema developed about 1 month later with desquamation the 

following week. About 4-5 months after exposure, the area began to ulcerate, with the 

extensive ulceration seen here at 1½ years after exposure. He eventually underwent 

skin grafting. 





Slide 37 

Although the fetus receives a lower radiation dose than does the mother from external 

sources (because of the womb and other overlying maternal tissues, fetal health 

consequences can be severe, even at radiation doses too low to immediately affect the 

mother. 

The human embryo and fetus are particularly sensitive to ionizing radiation because of 

their high rate of cell division (mitosis). 

Consequences can include growth retardation, malformations, impaired brain function, 

and cancer. Effects vary greatly based on gestational age and dose. 

Pregnant women should consult with their physicians if they have any concern about 

radiation exposure to their unborn baby. Physicians can find helpful information at the 

CDC’s Bioterrorism website, and in consultation with radiation experts. 





Slide 38 

Even during a radiological incident, medical triage is the highest priority. Radiation 

symptoms occurring in the first 24 hours after a total or partial body exposure are seldom 

life-threatening; therefore, all critical medical and traumatic issues should be addressed 

first. As long as it is safe and practical to do so, stabilization should take priority over 

decontamination. 

Examples of traumatic and medical issues include bleeding, injuries from shrapnel, blast 

effects, collapsed lung (pneumothorax), dirty wounds, or medical complaints of chest 

pain and difficulty breathing. 

Time, distance and shielding are the most important determinants of radiation exposure 

dose. These should be considerations during the initial triage, decontamination, and 

management of patients contaminated with radioactive material, but does not have any 

relevance for those who have been irradiated only. 

The photo depicts an assessment for potential extremity injuries as part of the initial 

patient evaluation/stabilization. Note that the provider is cutting the clothing in a direction 

away from the patient’s airway and is folding the potentially radioactive materialcontaminated 

portion outwards to keep any contamination off the patient’s skin. As will 

be discussed later, another individual could be doing a radiation survey for potential 

radioactive contamination. 





Slide 39 

As an example of the low likelihood of medical personnel being secondarily 

contaminated, the decontamination process for workers at Chernobyl who were in the 

reactor area at the time of the nuclear accident resulted in less than 10 mGy (1 rad) of 

radiation exposure to the members of the medical team. This is equivalent to the 

radiation of one CT scan of the pelvis. 

In April, 1986 the Chernobyl nuclear power plant in the Ukraine had an event that 

contaminated a broad region and exposed thousands of people. By far, the most highly 

exposed and contaminated people were the fireman who first responded to the event 

and attempted to put out the fire. Many of these men suffered from Acute Radiation 

Syndrome and all were highly contaminated. 





Slide 40 

Hospital staff are well versed in protecting themselves and their work areas from 

microbiological contamination through the use of standard precautions. The same 

techniques can be used effectively to protect personnel and the work area from 

contamination by radioactive materials. While fitted particulate respirators such as N95 

or higher will provide a higher level of protection against potential inhalation of 

radioactive particulates, a surgical mask is usually adequate protection unless there is 

concern of alpha particle contamination. 

Frequent use of a radiation survey meter (Geiger counter) by a dedicated staff person 

(usually the Radiation Safety Officer or designee) can alert personnel to areas of 

contamination, adequacy of decontamination, and the need to change their gloves or 

clothing when workers become contaminated, and to avoid spread of radioactive 

contamination in or outside the work area so that cleanup and extra precautions can be 

implemented. Such ease of detection and control is not possible with any other type of 

hazardous material. 





Slide 41 

A special treatment area layout should be established within existing emergency 

treatment areas to minimize the spread of any radioactive contamination. The major 

features of this layout are depicted in the slide and consist of a single point of egress (via 

the “step off pad”) separate from the room entrance that allows monitoring of personnel 

or equipment for contamination by radiation survey personnel, and a separate individual 

in the treatment area to survey the patient, his/her wounds, and the patient 

decontamination process. 

The contaminated area (thought of as the “hot zone”) is separated from the remainder of 

the department (the clean area or “cold zone”) by a buffer zone (warm zone). Exiting 

personnel are monitored for contamination (while still on the step off pad) and 

contaminated gloves, shoes, coveralls, or other materials can be placed in receptacles 

set aside for them before stepping off the pad. At that point, a whole body survey is 

conducted with a radiation meter, taking special note of hands, feet and face. 

Other modifications to “standard precautions” that are appropriate for the management 

of patients contaminated with radioactive material are reviewed in the next few slides. 





Slide 42 

Carefully remove and bag patient’s clothing and personal belongings, which typically 

removes 80 - 90% of contamination. These should be put in a double bag, tied, sealed 

and labeled. Unfamiliar embedded objects in patient’s clothing or wounds may be 

radioactive sources. Handle these objects with long forceps, handle only briefly, and 

keep distant from staff and patients until proven, with a survey meter, not to be 

radioactive. If radioactive objects are recovered, they should be placed in a container 

using tongs or forceps. 

Survey the patient for contamination after clothing removal, using a consistent pattern to 

provide a complete survey. 





Slide 43 

Decontaminate patients with several gentle efforts, rather than with a single aggressive 

effort. Soap and water are sufficient. 

Remove contaminated hair if necessary, using scissors or electric clippers. To avoid 

cutting the skin and providing an entry for internal contamination, do not shave. 

Use occlusive dressings to promote sweating and removal of persistent contamination 

from pores. 

Survey areas with a Geiger counter frequently until decontamination is complete. 

Once clothing is removed, decontamination should begin with any open wounds as there 

is greater chance of internal contamination from these. A face shield should be placed 

over the patient’s lower face to prevent splashing or movement of radioactive material 

towards the mouth and nose (to prevent ingestion/inhalation). 

If localized contamination persists after washing, cover the area with gauze and put a 

glove or tape plastic over the area to promote sweating as this may remove additional 

material from pores. 





Slide 44 

In a radiation contamination event, any wound must be considered contaminated until 

proven otherwise and should be decontaminated prior to decontaminating intact skin. 

Protection of non-contaminated wounds with waterproof dressings will minimize the 

potential for uptake of radioactive material. To decontaminate wounds, irrigate and 

gently scrub with a surgical sponge. Normal wound debridement should be performed. 

Excision around wounds solely to remove contamination should only be performed in 

extreme cases. 

Placement of gauze within a wound or over a denuded area will remove additional 

contamination. 

When wounds are contaminated, the physician must assume that incorporation (internal 

contamination) has occurred. Appropriate action is based on both radioactive and 

biologic half-life, radiotoxicity (type of radiation), and the amount of radioactive material. 

It is important to consult experts as soon as possible and to initiate measures that 

prevent or minimize uptake of the radioactive material into body cells or tissues. 





Slide 45 

Radioactive material can sometimes enter the body through inhalation, ingestion, or a 

dermal wound. Deposition of radioactive materials in the body is a time-dependent 

physiological phenomenon related to both the physical and chemical natures of the 

contaminant. 

Internal contamination does not cause early signs or symptoms. 

While it remains inside the patient internal contamination will continue to irradiate the 

patient, though probably not harm others. 

Swabs of the nares should be assessed for radioactivity by the survey team. If internal 

contamination is suspected, arrange for additional bioassays of the patient. These could 

include analysis of blood, urine, feces, perspiration, nasal and saliva swabs, sputum, 

vomitus, and wound secretions, and will vary somewhat based on the particular 

radioactive isotopes. 





Slide 46 

There are certain specific medical therapies for the treatment of patients with internal 

contamination with radioisotopes. We will look at a couple of these in more detail. 

It is important to remember that removal of the element from the body also removes the 

radiation – and the biologic half-life of many elements is often shorter than the radiologic 

half-life of their radioactive forms. 





Slide 47 

Prussian Blue (Radiogardase) is an FDA-approved treatment for victims of a “dirty 

bomb” who are internally contaminated with radioactive Cesium or Thallium. This 

chelator forms high affinity, nonabsorbable complexes with cesium and thallium. 

After oral administration, this compound decreases gastrointestinal absorption of Cs and 

Th. It also interrupts the recycling of these compounds from the systemic circulation 

through the bile and back into the gut. This increases the elimination of the radioactive 

elements from the body in the feces. 





Slide 48 

Another chelating agent is DTPA, which is generally given IV. It is used to bind larger 

radioactive elements such as plutonium. There are two forms of DTPA, one complexed 

with calcium, the other with zinc. Calcium DTPA is more effective in the first 24 hours 

after exposure, but Zn-DTPA is recommended for delayed or ongoing therapy. These 

agents exchange the calcium or zinc for the plutonium or other transuranic element 

(curium, americium) and the complex is excreted by the kidney in the urine. 





Slide 49 

Going back to the initial management of an exposed patient: 

Triage should identify acute medical and surgical issues; these will take priority in patient 

care. 

The setting of exposure should be identified, as well as the nature and timing of any 

symptoms (primarily onset of nausea/vomiting) to assess for the likelihood and 

prognosis of acute radiation syndrome, localized radiation injury, or a combination of 

effects. 

Early involvement of a radiation safety officer is important for dose assessment and to 

provide information that will guide subsequent radiation-related therapy 

These patients will be scared, particularly since most will be relatively well on initial 

presentation, unless injured by shrapnel or other trauma. 





Slide 50 

Given the infrequency of radiation exposure in modern healthcare, consultation with 

experts is very important. The radiation safety officer or health physicist can aid in 

identifying radioactivity and the extent of contamination, as well as in the safe disposal of 

radioactive waste. These experts can also help guide the specimen collection and 

interpretation of symptoms and laboratory findings from irradiated or radioactivelycontaminated 

patients. 





Slide 51 

On November 1, 2006, former Russian spy Alexander Litvinenko suddenly fell ill and 

was hospitalized. He died three weeks later, becoming the first known victim of lethal 

polonium-210-induced acute radiation syndrome. Traces of polonium were found in his 

urine, at his home, and at a London restaurant and hotel he visited the day he became 

ill, and traces were found elsewhere, suggesting involvement of Russian agents. 





Slide 52 

Polonium-210 is an alpha-emitter, but its particle is of particularly high-energy. Polonium- 

210 gives off 5,000 times more alpha particles than does the same amount of radium, 

another alpha-emitting radioisotope. 

Polonium’s high energy alpha particles can severely damage genetic material (DNA) if 

able to reach it. Since alpha particles only penetrate short distances, polonium is only 

harmful to humans through inhalation, ingestion, or contact with open wounds. 





Litvinenko stated that he met with two former KGB agents (one of whom is an Italian 

security expert) early on the day he fell ill with abdominal pain, nausea, vomiting, and 

diarrhea; and was hospitalized. A British toxicologist suggests thallium poisoning, which 

is not an unreasonable thought early on. However the subsequent clinical course was 

not consistent with thallium. 

In addition to the claims and counter-claims made by many people, this murder has an 

important clue – the traceable alpha-emitter polonium-210, which has a radiologic halflife 

of 138 days. Thus the path of this radioisotope remains for many months. 

Alexander Litvinenko died November 23, 2006, just over 3 weeks post-exposure. 

Slide 54 

It is commonly said in medicine that the history makes the diagnosis. In these cases the 

key historic feature is identifying a possible radiation exposure. Some possible scenarios 

include: 

- Finding an unknown metallic object, as we saw in the Goiania Brazil event. 

- A history of working with radioactive chemicals, such as fluorescence spectroscopy, 

industrial radiography, etc; or working in a potential site for exposure, such as 

construction or a scrap metal yard. 

- Multiple people falling ill simultaneously with gastrointestinal effects, particularly with 

suggestive subsequent physical exam findings (such as skin lesions) 





Slide 55 

To review, some clues identifiable during the physical examination or routine laboratory 

testing may also suggest radiation injury: 

- Skin ulceration, skin peeling (desquamation), skin redness (erythema), loss of hair or 

abnormal sweating of an area of skin which can be seen with exposure to beta-emitters 

or localized injury from gamma or X-rays (often in association with findings of acute 

radiation syndrome[ARS], such as): 

- Unexplained infections or bleeding, particularly in the gums or gastrointestinal tract 

usually seen a week or more into an episode of ARS. 

- Weight loss, diarrhea, fluid or electrolyte imbalance, kidney failure; all as a component 

of the multi-organ failure associated with severe ARS. 

- Shock, connfusion, disorientation, brain edema, loss of coordination (ataxia), seizures, 

or coma (1-2 days after a massive radiation exposure). 





Slide 56 





Slide 57 

The key points made in this presentation include: 

Stabilization is the highest priority. Patients die of their injuries much faster than they do 

from radiation poisoning. 

Radiation experts should be consulted liberally given the relatively uncommon 

opportunity for any individual clinician to care for an exposed patient. 

Training and drills should be offered for all forms of hazard response. 

Adequate supplies and survey instruments should be stocked, and they should be 

accessible and in working order. 

Standard precautions reduce contamination of the healthcare provider. 

Early symptoms and their intensity indicate the severity of the radiation injury. These 

should be inquired about, observed, and recorded. 





Slide 58 





Module Seven Summary 

Radiation is an especially powerful terrorism weapon because it instills considerable fear. 

Terrorist acts or threats involving radioactive materials are broadly categorized into radiologic 

events, which involve the non-nuclear release of radioactive materials, and nuclear events 

involving nuclear weapons. There are four major radiologic terrorist scenarios including, as 

examples, radiation sources intentionally hidden in public places or dispersed widely in 

communities; radiologic dispersion devices (RDDs or dirty bombs); attacks on nuclear facilities 

or radioactive materials in transit on trucks and trains that result in intentional release of 

radioactive materials. 

RDD employs conventional explosives to disperse radioactive materials. RDD events may result 

in physical injuries, variable radiation contamination, and psychological trauma to a population. 

The severity of physical injuries depends on the nature of the explosives used, and the extent of 

contamination depends on the degree to which the radioactive material is dispersed. Dispersal 

is dependent on the physical and chemical form of the radioactive material, the explosives, and 

the atmospheric conditions. 

Certain radioisotopes used in industrial and medical devices could be positioned to cause 

serious exposure to an unsuspecting population. An estimated 2 million devices in the USA 

contain licensed radioactive sources, but there is no comprehensive national inventory tracking 

these industrial sources of radiation. Companies have reported losing track of almost 1700 

sources since 1998. More than half have yet to be found. 

Radiation injury occurs through ionization of water molecules leading to the production of free 

radicals, which directly cause organelle and cellular damage. Ionization can also break covalent 

bonds in macromolecules such as proteins and DNA and lead to changes in the biologic or 

chemical function, particularly when cellular repair mechanisms are ineffective. In acute injury, 

the risk of cellular damage is proportional to the total absorbed dose, becoming clinically 

apparent in organ malfunction or failure when significant numbers of cells have been damaged. 

Rapidly dividing cells, such as intestinal mucosal cells and blood-producing cells, are the most 

susceptible. 

Unlike thermal burns, where tissue injury is quickly apparent, cutaneous radiation injuries (CRI) 

findings are delayed. Early signs and symptoms (within hours) include itching, tingling, and 

transient skin reddening or swelling. This is followed by a symptom-free latent period of days to 

weeks, and then, depending on the dose, by intense skin reddening, blistering, peeling, and 

ulceration that may occur in several waves. In cases of high-dose exposures, irreversible tissue 

damage may occur and result in permanent hair loss, damaged sebaceous and sweat glands, 

tissue atrophy and fibrosis, alterations in skin pigmentation, and tissue necrosis. 

When acute whole-body exposure to high doses of penetrating radiation occurs, acute radiation 

syndrome (ARS) may result. ARS is the manifestation of radiation induced cellular death and 

deficiency in hematopoietic, gastrointestinal, and neurovascular tissue. Damage to these tissues 

results in clinical presentations termed the hematopoietic, gastrointestinal, and neurovascular 

(or central nervous system) syndrome, respectively. 

ARS occurs only above a threshold dose of about 0.7 Gy of penetrating radiation. With 

increasing doses, onset of the syndrome is more rapid, and the ARS is more severe and 

includes an increasing number of tissue types. ARS is described in 4 stages: the prodromal 

stage, the latent stage, the manifest illness stage, and recovery or death. The prodromal stage 





occurs as early as minutes after exposure and lasts for up to several days. During this time, 

nausea, vomiting, anorexia, and, depending on dose, diarrhea occur. In the latent stage, the 

patient will feel generally well for hours to days. Timing and duration of the latent stage is also 

variable and dose dependent. The manifest illness stage occurs next, and the type of illness 

depends on the dose received and the type of syndrome, or syndromes, that occurs. 

At doses in the range of 0.7–10 Gy, the full hematopoietic syndrome occurs. Bone marrow 

depression leads to reduced white blood cell and platelet counts, with subsequent hemorrhage 

and infection. Patients exposed to lower doses recover over periods of weeks to a year. 

At doses above 1.2 Gy, the mortality rate for the hematopoietic syndrome increases, and the 

60-d median lethal dose (LD50) is 2.5–5 Gy. Death due to the hematopoietic syndrome occurs 

within a few months of exposure. 

At doses greater than 10 Gy (though known to occur at doses as low as 6 Gy), the 

gastrointestinal syndrome occurs as a result of intestinal mucosal stem cell death. This leads to 

fluid and electrolyte imbalance, dehydration, shock, and hemorrhage. In patients who develop 

the gastrointestinal syndrome death usually occurs within 2 weeks. 

At even higher doses (20 Gy), the neurovascular syndrome occurs. Damage to neurovascular 

tissue leads to hypotension, cerebral edema, seizures, and invariable death, often within 3 days 

of exposure. 

The management of patients with radiation exposure includes supportive care, care for other 

injuries, and assessment for signs of poor prognosis. The latter signs include rapid onset of 

symptoms, gastrointestinal complaints, and a falling white blood cell count (lymphocyte number) 

measured by the Andrews nomogram. 

Decontamination is only relevant for patients who are contaminated, that is those with dermal or 

internal radioisotope deposition. Exposure to ionizing beams of radiation do not leave a patient 

radioactive or with the need for (or possibility of) decontamination. 

Expert consultation can be obtained locally through the radiation safety officer or medical 

physicist at most medical centers or through the Radiation Emergency Assistance 

Center/Training Site (REAC/TS) consulting service in Oak Ridge, TN. 





Module Eight 

Observed Behaviors during Mass Chemical Exposures- 


Mass chemical exposures, irrespective of their cause, have understandably resulted in 

considerable public anxiety. While public reaction to such events is not, per se, a toxicological 

issue, the burden placed on health care and triage systems by the “worried well” is an important 

concern for everyone involved in the management of such a crisis. Anticipating demand and 

encouraging communication are key elements in ensuring effective care and preventing public 

hysteria. 

Duration 

45 minutes 


Using illustrative examples, this module explores common stress reactions to mass chemical 

exposures with a view towards attenuating their potential impact. 


• Understand how to anticipate and appropriately respond to 

psychological issues encountered in victims of real & perceived 

chemical exposures 


Resources 

• Describe expected behaviors of large groups of people after a 

perceived toxic chemical exposure 

• Recognize the signs and symptoms of acute psychological and 

emotional response to a traumatic event (e.g. disaster or fear of real 

or perceived toxic chemical exposure 

• Develop a strategy to aid victims with fear/strong emotions following a 

real or perceived toxic chemical exposure 













1. Ali-Gombe A, Guthrie E, McDermott N. Mass hysteria: One syndrome 

or two British Journal of Psychiatry 1996;168(5):663-665. 

2. Auf der Heide E. Convergence behavior in disasters. Ann Emerg Med. 

2003;41(4):463-466. 

3. Bartholomew R. Mass hysteria.[comment]. British Journal of 

Psychiatry 1997;170:387-388. 

4. Benedek D, Holloway H, Becker S. Emergency mental health 

management of bioterrorism events. Emerg Med Clin N Am. 

2002;20:1-15. 

5. Black D, Welch F, Murray V. Mass psychogenic illness attributed to 

toxic exposure at a high school [letter]. New England Journal of 

Medicine 2000;342(22):1674. 

6. Bleich A, Dycian A, Koslowsky M, Solomon Z, Wiener M. Psychiatric 

implications of missile attacks on a civilian population: Israeli lessons 

from the Persian Gulf War. Journal of American Medical Association. 

1992;268(5):613-615. 

7. Boss LP. Epidemic hysteria: a review of the published literature. 

Epidemiologic Reviews 1997;19(2):233-243. 

8. Bowler R, Mergler D, Huel G, Cone J. Aftermath of a chemical spill: 

Psychological and physiological sequelae. Neurotoxicology. Fall 

1994;15(3):723-729. 

9. Boxer P. Occupational mass psychogenic illness: History, prevention 

and management. Journal of Occupational Medicine. Dec. 

1985;27(12):867-872. 

10. Clauw DJ, Engel CC, Jr., Aronowitz R, et al. Unexplained symptoms 

after terrorism and war: an expert consensus statement. Journal of 

Occupational & Environmental Medicine. 2003;45(10):1040-1048. 

11. Clements CJ. Mass psychogenic illness after vaccination. Drug 

Safety. 2003;26(9):599-604. 

12. Cole LA. Bioterrorism threats: learning from inappropriate responses. 

J Public Health Manag Pract. 2000;6(4):8-18. 

13. Cole TB, Chorba TL, Horan JM. Patterns of transmission of epidemic 

hysteria in a school.[see comment]. Epidemiology. 1990;1(3):212-218. 

14. Colligan M. Mass psychogenic illness: Some clarification and 

perpectives. Journal of Occupational Medicine. Sept. 1981;23(9):635- 

638. 

15. Colligan M, Murphy L. Mass psychogenic illness in organizations: An 

overview. Journal of Occupational Psychology. 1979;52:77-90. 

16. Colligan M, Smith M. A methodological approach for evaluating 

outbreaks of mass psychogenic illness in industry. Journal of 

Occupational Medicine. Jun. 1978;20(6):401-402. 





17. Durodie B, Wessely S. Resilience or panic The public and terrorist 

attack. Lancet. 2002;360(9349):1901-1902. 

18. Engel CC, Jr. Outbreaks of medically unexplained physical symptoms 

after military action, terrorist threat, or technological disaster. Military 

Medicine. 2001;166(12 Suppl):47-48. 

19. Engel CC, Jr., Adkins JA, Cowan DN. Caring for medically 

unexplained physical symptoms after toxic environmental exposures: 

effects of contested causation. Environmental Health Perspectives. 

2002;110(Suppl 4):641-647. 

20. Faust H, Brilliant L. Is the diagnosis of "mass hysteria" an excuse for 

incomplete investigation of low-level environmental contamination 

Journal of Occupational Medicine. 1981;23(1):22-26. 

21. Gallay A, Van Loock F, Demarest S, Van der Heyden J, Jans B, Van 

Oyen H. Belgian coca-cola-related outbreak: intoxication, mass 

sociogenic illness, or both American Journal of Epidemiology. 

2002;155(2):140-147. 

22. Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and 

chronic fatigue syndrome: a systematic review.1997;223-233. 

23. Chisholm D, Godfrey E, Ridsdale L, et al. Chronic fatigue in general 

practice: economic evaluation of counselling versus cognitive 

behaviour therapy Br J Gen Pract 2001;51(462):15-18. 

24. Holloway HC, Norwood AE, Fullerton CS, Engel CC, Jr., Ursano RJ. 

The threat of biological weapons. Prophylaxis and mitigation of 

psychological and social consequences. JAMA 1997;278(5):425-427. 

25. Jones TF, Craig AS, Hoy D, et al. Mass psychogenic illness attributed 

to toxic exposure at a high school. New England Journal of Medicine. 

2000;342(2):96-100. 

26. Karsenty E, Shemer J, Alshech I, et al. Medical aspects of the Iraqi 

missile attacks on Israel. Isr J Med Sci. 1991;27:603-607. 

27. Kawana J, Ishimatsu S, Kanda K. Psycho-physiological effects of the 

terrorist sarin attack on the Tokyo subway system. Military Medicine. 

2001;166:23-26. 

28. Landauer MR. Physiological and Psychological Impact of Low-Level 

Radiation: An Overview. Military Medicine. 2002;167(Suppl. 1):141- 

142. 

29. Levine RJ. Is the presence of low-level environmental contamination a 

sufficient excuse for not diagnosing mass hysteria Journal of 

Occupational Medicine. 1981;23(9):597-599. 

30. Moscrop A. Mass hysteria is seen as main threat from bioweapons. 

BMJ. 2001;323(7320):1023. 

31. Murakami H. Underground: The Tokyo gas attack and the Japanese 

psyche. New York: Random House; 2000. 






32. Okumura T, Suzuki K, Fukuda A, et al. The Tokyo subway sarin 

attack: Disaster management, Part 2: Hospital response. Academic 

Emergency Medicine. 1998;5(6):618-624. 

33. Okumura T, Takasu N, Ishimatsu S, et al. Report on 640 Victims of 

the Tokyo Subway Sarin Attack. Ann Em Med. 1996;28(2):129 - 224. 

34. Pastel RH. Collective behaviors: mass panic and outbreaks of multiple 

unexplained symptoms. Military Medicine. 2001;166(12 Suppl):44-46. 

35. Quigley C. Dual-edged sword: dealing with the media before, during, 

and after a weapon of mass destruction event. Military Medicine. 

2001;166(12 Suppl):56-58. 

36. Rifkin A. Mass psychogenic illness attributed to toxic exposure at a 

high school.[comment]. New England Journal of Medicine. 

2000;342(22):1674-1675. 

37. Romano J, King J. Psychologica and neuropsychological sequelae of 

chemical terrorism. In: Flora S, Romano J, Baskin S, Sekhar K, eds. 

Pharmacological Perspectives of Toxic Chemicals and Their 

Antidotes. New Delhi: Narosa Publishing House; 2004:1-11. 

38. Taylor BW, Werbicki J. Pseudodisaster: A case of mass hysteria 

involving 19 school children. Pediatric Emergency Care. Aug. 

1993;9(4):216-217. 

39. Wessely S. Responding to mass psychogenic illness.[comment]. New 

England Journal of Medicine. 2000;342(2):129-130. 

40. Wessely S, Wardle C. Mass sociogenic illness by proxy: Parentally 

reported epidemic in an elementary school. British Journal of 

Psychiatry. 1990;157:421-424. 

41. Nanagas KA, Kirk MA. Perceived poisons. Medical Clinics of North 

America. Nov 2005;89(6):1359. 

42. Martin-Gill C, Baer AB, Holstege CP, et al. Poison centers as 

information resources for EMS in a suspected chemical exposure. J 

Emerg Med 2007;32(4):397-403. 

43. Sandman P. Crisis communication: Guidelines for action. Accessed 

January 16, 2005. http://www.psandman.com/handouts/AIHA- 

DVD.htm. 

44. US Department of Health and Human Services. Communicating in a 

Crisis: Risk Communication Guidelines for Public Health Officials; 

2002. http://www.riskcommunication.samhsa.gov. 






















Module Eight 

Icon Map 






instruction 





Slide 1 


Module Eight 

Observed Behaviors during 

Mass Chemical Exposures 


1 

The psychological aspects of a mass exposure event are increasingly recognized as 

critically important issues for education and disaster planning. At first, this may NOT 

appear to be a toxicological problem. We cannot explain these symptoms through a 

simple receptor interaction. We do not have a specific toxic syndrome to identify this 

condition. We do not have an antidote to reverse this condition. However, applying the 

toxicologic principles of exposure pathway, dose-response, and clinical evaluation will 

allow emergency planners, emergency responders, and all health care providers to more 

effectively address commonly observed behaviors. 

Using illustrative examples, this module explores common stress reactions to mass 

chemical exposures with a view towards attenuating their potential impact. 





Slide 2 



Learning Objectives 

By the end of this module participants will be able to: 

• Understand the psych impact of mass chemical exposures 

• Provide appropriate response to the mental health needs of 

victims of real & perceived events 

• Describe expected behaviors of large groups of people after 

a perceived toxic chemical exposure 

• Recognize signs & symptoms of acute psychological / 

emotional response to a traumatic event 

• Develop a strategy to aid victims with fear/strong emotions 

following a real or perceived toxic chemical exposure 

Module One – Observed Behaviors during Mass Chemical Exposures 

2 

This module provides a framework to understand what is often characterized as “mass 

hysteria”. This term – though in common use – fails to recognize the normal physiologic 

process that often leads to progressive symptoms and disability in the setting of a 

perceived toxic chemical exposure (or other fear-provoking event). There are several 

characteristic features of crowd response. However, sorting out physical responses to a 

toxic exposure from physiological and psychological responses to a stress stimulus can 

take time and may be challenging. 

Large numbers of people present after mass disasters with physiologic stress response. 

The term “physiologic” is used to describe normal or exaggerated body response – the 

so-called “fight or flight” response to a stress or fearful event. While the examples 

provided in this module highlight some of the classic stress symptoms, it should be 

emphasized that there is often a degree of diagnostic uncertainty inherent to these 

events. 

In the absence of a concerned and knowledgeable response, the fear reaction may 

escalate resulting in more symptomatic individuals and more lasting symptoms. People 

assessed as having stress reactions should be provided care. Proper planning is 

required so they do not overwhelm the acute care system. 





Slide 4 



Audience Response Question 

Fifty people complain of nausea and several vomit 

after smelling a sulfur -like odor. Which of the 

following is the most likely explanation 

1. Hydrogen sulfide poisoning 

2. Food poisoning 

3. Mass psychogenic illness 

4. Panic 


4 

Slide 5 



Case 1: “The Toxic Lady ” 

• A 31 year-old cancer patient is rushed by EMS to the nearest 

LA suburb ED on March 19th, 1994. 

– An “oily sheen ” is noted on her chest. 

• During the resuscitation, a nurse drawing her blood notices a 

peculiar acrid smell that seems to be coming from the patient 

and passes out. 

• The senior EM resident picks up the syringe used to draw the 

blood and notices yellow crystals, smells it, collapses. 

– Within minutes, 4 more care providers are “overcome. ” 

• During the ensuing evacuation the patient dies 


5 

Let’s consider a few specific cases that highlight important aspects of psychological 

response to mass exposures. Several years ago, a very ill patient with metastatic 

cancer was brought by ambulance to a Los Angeles area hospital. During her initial 

evaluation, an unpleasant odor was noted, as well as an oily sheen to the skin. Health 

care providers participating in the resuscitation attempt passed out, causing others to 

evacuate the emergency department. The patient died and several providers were 

hospitalized. 





Slide 6 



Case 1: Leading Theories 

• Patient drank pesticide in suicide attempt or used a 

solvent (DMSO) as a home cancer remedy 

• Hospital plumbing emitted a toxic gas 

• A secret methamphetamine lab operated in the 

hospital basement. 

• “Mass hysteria ” 


6 

Several theories were proposed to explain this event. Given an odor and possible 

abnormal substance on the patient’s skin, an ingestion of undefined “pesticide” was 

proposed. Dimethyl sulfoxide (DMSO) is an industrial solvent used as an alternative 

cancer therapy. Other theories focused on a source within the hospital, including some 

outlandish suggestions, such as releases from a clandestine methamphetamine 

laboratory within the hospital. 

Despite the apparently genuine and severe illnesses of the ER staff, no satisfactory toxin 

that could have caused their illnesses has been identified. This has led to speculation as 

to whether so-called “mass hysteria” could have caused the symptoms experienced by 

the ER staff. Opinions are still divided as to the cause of the incident, without a clear-cut 

answer. Subsequent litigation has also not provided clarification. 





Slide 7 



• 37 exposed 

Case 1: “The Toxic Lady ” 

– 11 noticed unusual smell 

• Description varied: garlicky, ammonia like, gas -like, or chemical - 

like 

– 26 did not notice odor 

• Paramedics who transported patients and drew 

blood in the ambulance noticed no odor and 

developed no symptoms 

• 23/37 developed at least one symptom 


7 

Of the 37 who were in close proximity to the event, only 11 reported noticing an unusual 

smell. The remaining 26 potentially-exposed individuals noticed no odor. While 23 of 37 

exposed eventually developed at least one symptom, the paramedics who transported 

the patient and drew blood in the ambulance – presumably with the closest contact and 

largest potential exposure - noticed no difference in odor and developed no symptoms. 

The lack of symptoms in those with a larger dose or longer time duration of exposure 

would argue against an inhaled toxic compound from the patient – this is in keeping with 

the concept of dose-response as described earlier in the course. 





Slide 8 



Case 1: Mass Psychogenic Illness or 

Toxic Exposure 

• 5 health care staff hospitalized 

– ED nurse hospitalized for 9 days developed chronic 

severe headaches, fatigue, dyspnea 

• A psychiatrist insisted it was an organic cause 

– ED physician hospitalized in ICU for 2 weeks requiring 

mechanical ventilation 

• 3 months in a wheelchair 

• Avascular necrosis of knees requiring 20 operations 


8 

Two medical providers had significant hospitalizations, with ensuing chronic health 

issues - one with somewhat non-specific symptoms; the other with a more recognizable 

medical condition. These are serious health effects – but are they attributable to an 

original toxic exposure, consequences of medical interventions, or some combination 

thereof If the former, this would be strong evidence for a toxic exposure. If these 

effects are “just” adverse events based on physiologic and psychological responses to a 

frightening event and/or iatrogenic complications of procedures or medications, it 

underlines the importance of intervening in this process early. 





Slide 9 



Case 1: Three Investigations 

• Coroner 

– Patient died from cervical cancer 

– Fumes that sickened hospital workers were just the “smell of death ” 

• Cal-OSHA 

– No safety violations 

– Three employees had “involuntary psychological reaction to some 

agents” while the rest suffered from mass hysteria 

• California Dept of Health Services (CDC) 

– “An outbreak of mass sociogenic illness perhaps triggered by an o dor” 

– Also possible that a few staff members were exposed to unknown 

toxic chemical 


9 

The coroner’s report determined the cause of death to be cervical cancer, but found no 

chemicals that might account for the event. That report speculated that others were 

overcome by “the smell of death”. 

The official opinion of Cal-OSHA (state Occupational Safety and Health Administration) 

is that, while some of the staff may have been affected by hysteria, at least three people 

had a genuine reaction to some kind of toxin or agent. They also found no safety 

violations – meaning no methamphetamine laboratory in the hospital. 

The State Dept. of Health Services report said that most people (eventually over 30) who 

reported feeling ill were suffering from stress reactions, but that six staff who were felled 

may have been affected by either hysteria or a toxic agent. 

The Riverside Dept. of Health says that they now believe that the chief resident, a 

respiratory technician and a nurse with prolonged patient contact were not suffering from 

hysteria. 

Lawrence Livermore Lab released a report hypothesizing that dimethyl sulfate (an 

industrial gas with some irritant features and severe systemic effects) could have been 

produced from a dimethyl sulfoxide (DMSO) exposure or ingestion; and was the cause 

of toxic symptoms in some people. 





Slide 10 



What is the correct terminology to identify 

“mass psychogenic illness ” 

More Common Terms 

• Mass Sociogenic Illness 

• Epidemic Hysteria 

• Mass Hysteria 

• Traumatic stress response 

Less Common Terms 

• Epidemic transient 

situational disturbance 

• Psychosocial casualties 

• Environmental somatization 

syndrome 

• Psychological sequelae 

• Psychic possession 

• Crowd poison 


10 

A number of terms have been used to describe this type of response. Attempts to 

discuss and study this topic are problematic due to the highly variable terminology used 

to describe the underlying phenomenon. In a literature review Bartholomew reported the 

use of over 76 different terms referring to “mass psychogenic illness” like behavior. On 

the left of the slide are the terms that tend to be in current and common use, those on 

the right are less so. Psychic possession and Crowd Poison are particularly interesting 

terms. 

The existence of many terms and descriptive titles often indicates the difficulty in 

adequate definition or delineation of a disease or syndrome. 





Slide 11 



Definitions 

• Diagnostic and Statistical Manual of Mental 

Disorders -IV-TR 

– Epidemic Hysteria 

• Shared symptoms develop in a circumscribed group of people 

following "exposure" to a common precipitant. 

• Medical literature 

– Multiple Unexplained Symptoms 

• Typically chronic and not triggered by a specific event 


11 

A specific term is now used in the Diagnostic and Statistical Manual of Mental Disorders- 

IV-TR (DSM-IV) that describes the observed behaviors of groups exposed to an event. 

It is termed ‘epidemic hysteria.’ Although somewhat medicalized, this term carries a 

nonmedical meaning that may not be ideal (i.e., hysteria). 

A common term in the medical literature, but not in DSM, is Multiple Unexplained 

Symptoms (sometimes called Multiple Medical Unexplained Symptoms, MMUS; and 

other variants). This syndrome is very common, and while clinically similar in nature to 

epidemic hysteria, it is not generally triggered by a single event, is long standing, and is 

often pervasive in a patient’s life. Patients with this syndrome often come to attention in 

outpatient toxicology clinics with multiple previous physicians and diagnoses, and many 

tests showing normal or inconclusive results. 

The DSM is the standard manual for psychiatric diagnoses. It generally lists a number of 

criteria (symptoms, exclusion criteria, and timeframes) required for a consensus 

diagnosis of psychiatric conditions. The DSM-IV-TR is the fourth update (text revision) of 

this manual, published in 2000. 





Slide 12 



Be Careful What You Call It! 

• Condescending terms 

– Negative connotations 

– Hysteria implies individual is to blame for illness 

• Of course, physicians cannot have mass 

psychogenic illness 

– 1955 hospital epidemic with 300 affected 

• Once medical staff became affected, condition labeled as 

“epidemic benign myalgic encephalomyelitis ” 


12 

Our mental health colleagues warn us that the use of the term ‘hysteria’ has negative 

connotations. It implies that the individual is purposely causing the problems. “So you 

think it is all in my head” Thus the use in DSM, while medically acceptable, may not be 

externally acceptable. 

In 1955 a hospital epidemic occurred with 300 individuals affected. Once the medical 

staff became affected, the condition was labeled as “epidemic benign myalgic 

encephalomyelitis.” Physicians may liberally use the term “mass (or epidemic) hysteria” 

but in this particular incident, they quickly renamed it to avoid being accused of being 

hysterical themselves. 





Slide 13 



Case 2: Cyanide 

• 06:00 am 

– A pail caught fire at a plating company containing: 

• Sodium meta -nitrobenzene (85%) 

• Potassium cyanide (15%) 

• 15 workers of a downwind warehouse smelled 

smoke and noticed brief upper respiratory irritation 

• Evacuated to nearby (5 miles) airport facility but not 

informed of potential cyanide exposure 


13 

This next case highlights problems with communications and expectations in the setting 

of a possible mass exposure. On a cold January day in 1995 (Temperature 2 degrees 

F) a fire occurred in a plating company in Indianapolis, Indiana. Within an isolated room, 

a pail containing 85% sodium meta-nitrobenzene sulfonate and 15% potassium cyanide 

caught fire. Scrubbers filtered the escaping smoke from the room. 15 employees of a 

downwind warehouse noted the smell of smoke and brief irritant symptoms. The fire 

department evacuated nearby neighborhood including warehouse employees without 

informing them of potential cyanide exposure. The warehouse procedure was to 

evacuate to an airport facility (approx 5 miles away). The “All clear” was given at incident 

command because downwind air monitoring found no evidence of cyanide and 

calculations predicted no risk of cyanide release off of property. 







Case 2: Cyanide (Continued) 

• The original 15 evacuees and 85 contacts learned of 

cyanide exposure and several began complaining of 

chest tightness, nausea and dizziness 

• “Several are feeling ill and we ’ve got about 50 

people that were exposed over there, they ’re awake 

and oriented, they just wanted to be checked out. ” 


14 

Once everyone arrived at the evacuation site, they were informed of the chemicals 

involved in the fire. At that time – distant in time and varying greatly in their initial 

proximity to the event - several people began complaining of chest tightness, nausea 

and dizziness. 

Thirty minutes after the “All Clear” was given by the fire department, the county disaster plan 

was activated because these 100 individuals at the airport terminal were complaining or wanted 

to be checked to make sure they were OK. 





Slide 15 




• 9:30 am Incident Command decides 

– No decontamination at scene necessary 

– Transport to area hospitals 

• Hospital 1: 36 patients 



• 9:50 am Treatment and Disposition 

– Hospital 1: 

• Gross decontamination in parking lot 

• Lilly Cyanide Antidote Kit (N=2) 

• Media interviews with cameras rolling 

– Hospitals 2 & 3: Quick check and release 


15 

All patients were transported to three local hospitals. 

Hospital #1 received 36 patients. All were decontaminated outside the emergency 

department in the cold and two patients were administered Lilly cyanide antidote kit for 

symptoms. The antidote was administered based on subjective symptoms. A resident 

interviewed on camera stated, “Apparently we have a cyanide antidote and we gave it to 

patients with low oxygen saturation.” One patient receiving the antidote became 

hypotensive after treatment, requiring overnight ICU admission. 

Hospitals #2 and #3 received 52 and 12 patients, respectively. Evaluation without 

decontamination was performed at these sites. 

The media only filmed action at Hospital #1 where decontamination occurred - quite a 

spectacle in 2 degree weather. 





Slide 16 



Medical Personnel Responses 

“Cyanide is deadly. Cyanide is bad stuff! 

If it were me, I ’d go get checked out. ” 

• EMTs wearing surgical masks to drive. 

– Upset that patients were not decontaminated. 

• Medics c/o lightheadedness and smelled ‘bitter 

almonds’ 


16 

It is clearly a popular and correct belief that cyanide is deadly. What these statements 

and actions disregard is the clinical pharmacokinetics of cyanide poisoning. The time of 

onset (seconds to minutes with inhalation), clinical effects (multisystem collapse, not 

simply nausea and dizziness), and lack of utility of surgical masks to prevent cyanide 

exposure all went unrecognized or were ignored in the “heat of the moment”. Often in 

events like this, emergency response planners and health care providers, given their 

relatively prominent stature, can improve or worsen a situation by the messages they 

communicate and by the cues they provide by their actions. In this case it seems the 

“mass hysteria” was exacerbated, if not caused, by the medical community and 

emergency response crews. 





Slide 17 




• 12:30 pm media coverage 

– Footage and interviews from Hospital 1 

• Calls to Poison Center from: 

– Previously treated and released employees concerned 

they had not received “appropriate treatment ” 

– Hospitals 2 and 3 because several patients returned for 

“appropriate treatment ” 


17 

As soon as the noon news aired the story and showed the “appropriate treatment”, the 

regional poison center began to receive multiple calls from employees already released 

by the other hospitals. 

Because of the media coverage at Hospital #1, many who were treated at Hospitals #2 

and #3 returned for decontamination. Some patients returned to ED for additional care 

despite not having any symptoms. 





Slide 18 



Lessons Learned 

• Patients remote to exposure may exhibit symptoms 

– May develop symptoms on learning of the exposure 

• Medical personnel can be affected 

– They can become victims 

– They may react inappropriately 

• e.g., use therapies with potential for adverse reactions 

• Treatment for presumed poisoning can be harmful 

– Decontamination in extremely cold weather 

– Adverse effects of antidotes 


18 

We should recognize that patients who are remote to the exposure may complain of 

symptoms that cannot plausibly be linked to the exposure itself. 

They may even develop symptoms only after hearing about the exposure. Hearing 

about an exposure is not a valid exposure pathway for transmitting a toxin, but is an 

excellent pathway for transmitting fear. 

Medical personnel are humans too. They can be affected by fear, particularly in the 

absence of relevant knowledge (thus becoming victims or reacting inappropriately) 

Treatment for ‘presumed poisoning’ can be harmful as was seen in this case 

(decontamination in extremely cold weather, adverse effects of antidotes) 

These observations are important to incorporate into emergency planning. 





Slide 19 



Expect Large Numbers of Patients 

after Mass Chemical Exposure 

• Types of Patients 

• Obvious Medical Needs 

– Poisoned 

– Contaminated 

• Nonspecific symptoms 

– With no apparent exposure 

• Asymptomatic 

– “Just want to get checked out ” 

http://www.uli -atl.com/alerts_2007/alert_070118b.htm 


19 

Three distinct types of patients often present in HazMat or mass chemical exposure 

situations. Each group has different needs. Ideally, they should be identified and 

separated in the triage process. 

Obviously ill or - at least - contaminated individuals require treatment. A contaminated 

person is potentially poisoned, and potentially a risk to others, so should be assessed for 

symptoms related to exposure mechanism (e.g. inhalation) and agent, and assessed for 

the need for decontamination.. 

Others may have vague or non-specific symptoms. While it might be difficult to 

understand how victims in this group could have sustained a large enough exposure to 

become ill, they should be evaluated for any physiologic abnormalities (symptom nature 

and vital signs, screening physical exam – e.g. breath sounds, mucous membrane 

irritation) and reevaluated as adequate information becomes available regarding the 

exposure or if they become more symptomatic. 

Generally, the largest group of people just ‘want to get checked out.’ They just need 

reassurance that everything is OK. These people are similar to car crash victims that 

are fine but come to ED to get checked out. 





Slide 20 



Magnitude of Problem 

• Tokyo Sarin Incident 1995 

– 12 died 

– 1,200 required some care 

– 5,500 sought medical care but had no exposure 

• Bhopal Disaster 1984 

– >10,000 severe and 5000 died 

– 200,000 sought medical care 


20 

We have talked about several to one hundred individuals with these last two case 

studies. Consider the difficulty in managing an event of the magnitude of the Tokyo 

Sarin nerve agent attack by the Aum Shinryko cult and the Bhopal methylisocyanate 

industrial disaster in India. . 

The numbers of affected individuals in these cases are so large that victims overwhelm 

surge capacity of any system, create triage problems, and deplete scarce resources. 

Responders and providers are unable to focus care on the most seriously ill. Even small 

HazMat spills can result in many hundreds being transported to hospitals. Protocols are 

misguided if large numbers of unexposed “victims” are directed to acute-care hospitals 

just “to get checked out”. 





Slide 21 

During the 1991 United States–led Desert Storm operation, 39 Iraqi SCUD missiles 

landed in Israel. These attacks caused over 1000 casualties (including some traumatic 

injuries from explosives, shrapnel, and structural damage). However, one half of the 

casualties were diagnosed with acute psychologic reactions or acute anxiety. 

Also, because it was unknown if chemical weapons were part of the missiles’ payload, it 

appeared that people anticipated toxic chemicals and began to treat themselves without 

verification of chemical exposure or related symptoms. In one report, twenty-seven 

percent of the casualties were due to inappropriate autoinjection of atropine because of 

fear that a chemical nerve agent attack had occurred. 

Another 40 patients were injured while rushing to a sealed room to avoid chemical 

exposure. Some deaths occurred from improper use of gas masks leading to suffocation 

(including at least one child), while others succumbed to myocardial infarctions. Only 2 

deaths were due to missile trauma. 





Slide 22 



What is Panic 

• Panic is: 

– A sudden fear which dominates or replaces thinking [ wikipedia.org ] 

– A sudden unreasoning terror often accompanied by mass flight 

[www.merriam -webster.com ] 

• Often used incorrectly to describe any type of fear, flight, 

evacuation, or lack of coordination 

– Flight is often appropriate 

• Panic flight is 

– Irrational, hysterical or groundless flight 

– Reckless disregard for others 


22 

Panic is a term commonly applied to what is occurring in the minds of those exposed. 

Panic is different than the effects described so far (in which the threat is internalized and 

symptoms/signs develop.) In panic behavior, the person reacts irrationally to an event 

and runs or fights, etc. Sometimes flight is the appropriate thing to do (e.g., those 

individuals in the vicinity of the New York World Trade Center on the morning of 

9/11/2001). 





Slide 23 



Can People Panic during a Disaster 

http://scifipedia.scifi.com / 


23 

In July 1938 in a CBS Mercury Theater radio program that terrified the nation, Orson 

Wells broadcast a live presentation of H.G.Wells' science-fiction novel, War of the 

Worlds. Only later did much of the eastern seaboard realize that it was science fiction, 

not an actual extraterrestrial invasion. The following day, the New York Times front page 

announced: "Many flee homes to Escape Gas Raid from Mars...“ 

Slide 24 



Cycle of Fear and Perceived Poisoning 

• Perceived high risk of uncontrolled 

release of dreaded toxin 

• Input 

– Mucous membrane irritation 

– Lightheadedness 

– Noticing a bad odor 

– Observing friends become ill 

• Natural response is fear 

• Fear leads to autonomic arousal 

– Palpitation 

– Sweating 

• Autonomic arousal misinterpreted as 

a symptom of poisoning 


24 





Like it or not, we now live in a world of heightened awareness that a dreaded event is 

going to occur. If we have an unexpected input (irritation, funny odor, see a friend faint) 

then we may manifest a natural response - fear. Fear and anxiety lead to autonomic 

arousal (tachycardia – rapid heart beat, forceful heart beat – “pounding in the chest” – 

perhaps with increased blood pressure, sweating, tremor, lightheadedness, rapid 

breathing). Autonomic arousal occurs from release of epinephrine and norepinephrine 

from our adrenal glands. These symptoms may feel like a chemical exposure to the 

person and he/she becomes even more fearful. These symptoms are REAL, and 

reinforce the victim’s perception of being poisoned. In the absence of reassurance, 

evaluation, or recognition of this fear-arousal cycle, unexposed or non-poisoned people 

may panic, and one person panicking may lead to mass panic. 





Slide 25 



Panic is Rare During a Disaster 

• Observed groups of patients in period of impact 

– “Cool and Collected ” (75%) 

– Stunned and bewildered (>20%) 

– Confused, anxious, hysterical crying (




Slide 26 





Slide 27 



Case 3: A Gas Smell 

• A gas odor is noted in a school classroom 

• The teacher complains of headache, nausea, shortness of 

breath and dizziness 

• 80 students, 19 staff, 1 family member go to the ED 

– 38 hospitalized for unclear reasons 

• Scene investigation: no environmental cause 

– 5 days later school reopened 

• 71 people return to the ED for similar symptoms 

• Exhaustive investigation: no environmental cause 


27 

The last case we will discuss highlights some of the difficulties in ruling-out a toxic 

exposure and the resulting problems that situation creates. In November 1998, a teacher 

at the Warren County High School in McMinnville, Tennessee noticed a "gasoline-like" 

smell in her classroom, and soon thereafter she had a headache, nausea, shortness of 

breath, and dizziness. The school was evacuated, and 80 students and 19 staff 

members went to the emergency room at the local hospital; 38 persons were 

hospitalized overnight. An investigation did not identify any problems with spills, gas 

leaks or the like; and the school was reopened. However, symptoms reoccurred. 

Despite several intensive investigations, no contamination or toxin was identified. 







Features Suggestive of 

“Mass Psychogenic Illness ” 

• Rapid onset and recovery 

• Contagious, spreads via: 

– Sight (particularly “line of sight ”) 

– Smell 

• Diversity of symptoms w/o physical signs or abnormal labs 

• Benign morbidity with no sequelae 

– Though remember the “Toxic Lady ” 

• Often recurs when returning to environment 

• No reasonable organic basis 

– Environmental investigation is negative 


28 

When we evaluate cases of potential toxic mass exposure, there are certain features 

suggestive of mass psychogenic illness that we should recognize: 

Onset is generally immediate or rapid, often precipitated by sensing an odor or viewing 

another person getting “sick”. 

The clinical complaints are often variable between patients, and clinical evaluation 

proves negative. 

Most people recover quickly and have no long term morbidity, though patients can suffer 

self-harm unintentionally. 

Symptoms may recur due to lingering anxiety on re-entry, while concentrations of any 

noxious (unpleasant) agent or toxic compound is generally less due to ventilation and 

the passage of time. 

No toxic exposure is identified, or a potential exposure inconsistent with the toxidrome, is 

found. 





Slide 29 

In the high school case just described, these are the varied symptoms identified among 

the 91 people initially evaluated at the hospital. All are protean or nonspecific symptoms, 

and the findings varied among the patients, suggesting it is not due to an exposure to 

any given toxic substance. 





Slide 30 

. 

There are several features from this high school event that argue for Mass Psychogenic 

Illness. Perhaps the most important piece of evidence is the development of symptoms 

in a number of people not in the classroom where the odor was first noticed. When an 

investigation was conducted, no compounds were found beyond what would be 

expected in an occupied building. Of course, there are always criticisms as it is often 

difficult to “prove a negative”. 





Slide 31 

Of course, we do not want to miss actual poisoning events. In this sense, psychogenic 

illness is a diagnosis of exclusion. Note the similarity between many of the symptoms 

seen in minor nerve agent poisoning and stress-induced symptoms. Obviously as more 

severe effects develop, the syndromes become easier to differentiate. 





Slide 32 

Similar to minor nerve agent poisoning, low dose cyanide exposure can cause 

symptoms very similar to that of mass psychogenic illness. As cyanide poisoning 

progresses, the diagnosis becomes more obvious. 

Again, it is important to remember that psychological effects should be diagnosed with caution. 





Slide 33 



Is there a solution 

www.bu.edu 

commons.wikimedia.org 


33 

It requires some aspects of psychiatry and detective work to work through some of these 

cases – both the nature of the potential exposures and the likelihood of toxic vs. 

psychological symptoms (or a mixture). 





Slide 34 



Is it Real 

• Emergency Response 

– Don’t get caught up on figuring out if it exists or not 

– “Psychogenic illness ” is a diagnosis of exclusion 

– Create a “holding environment ” 

• Location away from high -tempo triage activities 

• Symptoms monitored and re -evaluated 

• Research 

– Need for good epidemiological data that clarifies 

characteristics of each group (defines needs) 


34 

Don’t ask this question. Assume it is real, until and unless you have very good evidence 

of psychogenic/stress-response symptoms only. 

People should be placed in as “low stress” an environment as possible and re-evaluated 

for under-triage based on a developing case definition as more information becomes 

available. Characterizing the response of various groups (e.g. vulnerable populations) is 

still an area that needs more research. 





Slide 35 



Planning Suggestions 

• Expect the problem – Plan for it 

• “Base disaster plans on what people are likely to do rather 

than what they should do ” 

Auf der Heide : Disaster Response: Principles of Preparation and Response 

• Don’t ignore these patients 

– And take them seriously 

• Early diagnostic & management decisions are critical to the 

success of the emergency response 

– EDs have little surge capacity 

– Decontamination and PPE burden the health care system 


35 

The problem of stress-response symptoms and their effect on both the number of people 

presenting for evaluation and the interpretation of clinical presentations is very real and 

should be incorporated into disaster planning. 

As one of the CDC–based emergency physicians has written, disaster plans should be 

based on what people are LIKELY to do, rather than what they SHOULD do. 

Since you can be sure that people will seek care if concerned or scared – and will not 

wait for an orderly triage or decontamination process in the field – we should plan to 

direct people arriving to our hospitals to an area that allows for secondary triage, to 

avoid overwhelming the acute care areas. Expert assistance should be sought to 

determine the actual need for decontamination, and the need for or level of personal 

protective equipment (PPE). 





Slide 36 



Training Suggestions 

• Teach emergency responders basic toxicology 

principles 

– e.g. Dose -Response (“dose makes the poison ”) 

• Look for objective signs of toxicity 

– Toxidrome recognition 

• Irritant Gas Syndrome 

• “Knock-down” or metabolic poisoning 

• Opioid intoxication 

• Cholinergic/Cholinesterase inhibitor 


36 

Emergency responders have an important role in evaluating patients and the scene of 

an event. Developing an appreciation for possible exposure pathways (e.g. inhaling a 

vapor or gas) and the effects of dose (identification of possible point source release and 

severity of symptoms based on proximity to same) are important pieces of information as 

we attempt to identify a toxic exposure or psychogenic symptom source. 

In a mass casualty event, approach patients looking for common elements that define a 

cluster of symptoms and signs (a toxidrome). We have not covered all of the possible 

syndromes in this course, but have provided a framework to apply to any situation. 





Slide 37 



Improve Communications 

• Information is the ANTIDOTE for fear 

• Make substance identification a priority and report to health 

care providers as soon as possible 

• Make inter-agency coordination a priority in planning 

– Strive for “single voice ” communications with the media and the 

public. When you speak, you speak for all of us! 

• Teach risk communication skills to ALL responders 


37 

Accurate information is the “antidote” for fear; but inaccurate or wrong information can 

be “poisonous”, resulting in frustration, mistrust and bad patient care. Previous disaster 

events illustrate the problem of communications during a crisis. Communications at all 

levels is crucial to emergency response planning. 

Accurate information and flow of information is critical to a successful emergency 

response. 

Plans should include contingencies for communication breakdown and problems with 

inaccurate and changing information. If the described symptoms do not fit the 

“identified” compound, seek verification. All early messages should stress the dynamic 

or uncertain nature of such information. Emphasize some of the common mistakes made 

with substance identification (e.g. hydrochloric acid for hydrofluoric acid) and the need to 

compare toxidromes with stated agents. 





Slide 38 



Unconventional Partnerships 

• Behavioral care experts 

• Epidemiologists 

– Develop tools to evaluate behaviors during catastrophic events 

– Evidence based planning based on Social -behavioral observations 

• Medical Toxicologists 

– Medical Toxicologists are clinical experts in the human health e ffects 

of poisoning 

– Accessed through ACMT, poison centers, or direct contact 


38 

Emergency response planning should utilize experts from a number of different areas, 

including behavioral health, epidemiology, toxicologists. The goal is to have a 

coordinated flow of information and resources to provide the most appropriate care to 

those who need it. Medical Toxicologists are experts in the area of human health effects 

from poisoning. We need to work closely with other experts to most effectively respond 

to mass chemical exposures. 

Uncertainty creates anxiety. The sooner the identification of the causative agent(s) is 

confirmed, the more reliable health risk information and treatment recommendations can 

be provided. 

Most importantly, ALL experts should work together within the National Incident 

Management System (NIMS) unified command structure so that a “single message” is 

given to the community. Conflicting information from “experts” will raise the anxiety of 

the community and may increase the number of victims seeking aid for reassurance or 

anxiety-induced physical symptoms. 





Slide 39 

There are many excellent sources of information to assist in planning including the CDC 

website and ATSDR Planning Guide depicted here. It is anticipated that the extent of 

future disasters can be minimized, particularly in terms of psychological casualties and 

inappropriate testing and treatment, by using expertise available to emergency 

responders and planners. 





Slide 40 



Summary 

• Expect large numbers of patients after mass chemical exposure 

– Often difficult to identify those needing immediate medical care 

• Avoid labels without objective diagnostic criteria 

– “Worried well ”, “Mass hysteria ” less helpful than “I know you are worried; 

things check out OK now. I will check on you again …” 

• Use historic lessons, expected behaviors to guide planning 

• Communication is Key 

– Interagency coordination may avoid needless fear 

• Know your resources and partner with them 

– Including ACMT/Medical Toxicologists 


40 

In summary, we should expect large numbers of patients after a potential mass chemical 

exposure; some will be in need of urgent treatment, some will have a variety of nonspecific 

stress-induced symptoms, and others will just be concerned. 

Rather than labeling these people, we should strive to acknowledge their concerns, 

assess their physical status and re-evaluate their condition. 

Planning for large numbers of patients with various needs should be a routine part of our 

disaster planning. Improving communication and utilizing the expertise available 

regionally and nationally are important steps in preparing for chemical terrorism and 

HazMat events. 





Slide 41 


Questions 


41 





Module Eight Summary 

The initial stages of a mass chemical exposure, particularly one of unknown origin or malicious 

intent, engender fear and anxiety in the general population and have the potential overwhelm 

clinical centers. After a mass chemical exposure the vast majority of individuals presenting for 

treatment or screening will be the worried well. Adding to the burden of identifying those who 

need immediate care and reassuring those who do not, stress reactions among patients (and 

medical personnel) may closely mimic the symptoms of certain chemical exposures. 

As was seen with past chemical exposure crises (1991 Gulf War concerns, 1995 Tokyo sarin 

attack, 1984 Union Carbide Bhopal disaster) patients remote from the event may exhibit 

symptoms. Given the added triage burden, medical personnel may be inclined to err on the side 

of caution when dealing with potentially exposed patients. However, injudicious or over-liberal 

application of decontamination procedures and aggressive antidotal therapies (e.g. atropine, 

cyanide antidote kit) can itself pose a risk to health. 

In order to minimize the added burden on the system and preempt unnecessary clinical visits it 

is critical that information regarding the event be rapidly and widely disseminated. In past 

crises, lack of communication between agencies and the absence of central guidance has been 

a major contributory factor. In order to effectively manage the public reaction to a crisis, the 

media’s message must be an integral part of the risk communication plan. 

Stress reactions to chemical release follow a somewhat predictable progression. This process 

begins when a subject becomes aware of the release or potential release of a dangerous toxin. 

Past studies have shown that the initial fear response is augmented or mitigated by the novelty 

of the agent at hand, the subject’s knowledge regarding the agent, whether or not antidotes or 

therapies exist for the treatment of this exposure, and whether or not the agent itself can be 

detected and/or identified. 

A natural fear that one has been exposed engenders a heightened awareness of body 

sensations. Minor symptoms or observations may become magnified thereby exacerbating the 

initial reaction and potentially leading to autonomic arousal. The outward signs of this autonomic 

arousal may be misinterpreted as symptoms of exposure. 

Further complicating matters, many of the non-specific symptoms relating to stress reactions 

may themselves closely mimic signs of chemical exposure (headache, dizziness, nausea, 

mucous membrane irritation, numbness, weakness, drowsiness). 

Disaster management and appropriate planning for a mass chemical exposure should focus on 

what people are likely to actually do during an emergency. While overt labeling of subjects as 

“hysterical” or “worried-well” can be stigmatizing, any response plan must consider the burden 

from both psychological and physical casualties. 

It is critical that triage staff not become preoccupied attempting to determine if a given exposure 

is “real”. As psychogenic illness is generally a diagnosis of exclusion, triage strategies should 

focus on identifying toxic syndromes and addressing objective signs of exposure. While caution 

is warranted, one should presume symptomatic patients are poisoned unless other evidence 

exists. 

Risk communication should be tightly coordinated to ensure all groups speak with the same 

voice. Careful interagency planning and coordination supported by risk communication training 

for staff is key. A comprehensive approach should focus on building partnerships between first 





responders, clinical staff, health departments, emergency services personnel, behavioral 

experts, and medical toxicologists.

Chemical Agents of Opportunity for Terrorism: TICs & TIMs

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?