Poisons and Drugs

Poisons and Drugs
Prof. Monzir S. Abdel-Latif
Chemistry Department
Islamic University of Gaza
http://www.monzir-pal.netpal.net

Syllabus
In this course, it is anticipated to cover the following topics:
1. Introduction to Toxicology
2. Epidemiological Studies
3. Toxicodynamics and Toxicokinetics
4. Toxicokinetics ...... Continued
5. Toxicokinetics ... continued
6. Risk Assessment and Management
7. Review of Analytical Methods
8. Drug Testing Methodologies and Possible Pitfalls

Methods of Analysis
1. Gas Chromatography
2. Liquid chromatography
3. Mass Spectrometry
4. Hyphenated Techniques
5. AAS and AES
6. Spectrophotometry and Fluorometry
Sample Preparation
Classes of drugs and poisons
1. According to site of action
2. Grouping of drugs

Drug Classification:
9. Amphetamines
10. Lysergic acid and LSD
11. Other Hallucination Drugs
12. Cannabis
13. Opiates and Cocaine
14. Therapeutic Drug Monitoring
15. Pesticides
16. Illicit Drugs Analyzed by the Forensic
Lab in Gaza

We will follow presentation chapters from several
textbooks including “Fundamantal
Toxicology” by John
Duffus and Howard Worth, published by RSC in 2006,
Poisoning and Toxicology handbook, 4 th Ed., A Guide to
Practical Toxicology, 2 nd Ed, Woolley, , Toxicological
Chemistry and Biochemistry, 3 rd Ed., as well as others .
However, other books in Instrumental Analysis and related
research papers will be found very helpful.
I’ll try to maintain a web page for the course and regularly
post reading material for you to look at.

Introduction to Toxicology
Toxicology is the fundamental science of poisons.
A poison is a substance that can cause severe injury or
death as a result of interaction with living tissue.
Therefore, in principle, all chemicals can be considered as
potential poisons causing injury or death upon excessive
exposure. At the same time all chemicals can be regarded
as safe if exposure to chemicals was kept below a tolerable
limit.

Exposure to toxins
Exposure is a function of the following factors:
Amount or concentration of the target chemical
Time of interaction of the chemical with the target organ
Frequency of interaction of the chemical with the target
organ
Organ exposed
For humans, age and health of the subject are also
important factors
For highly toxic chemicals, the tolerable exposure is close to
zero

Determination of tolerable exposure
In fact, this constitutes a problem since we do need
reliable data relating exposure to injury or adverse
effect in humans.
Unfortunately, what can be considered as an injury or
an adverse effect is not well defined and debatable.
We will look at this problem later

Adverse effects
An adverse effect can be defined as an abnormal,
undesirable, or harmful change of people or
organs following exposure to the potentially toxic
substance
Although the ultimate adverse effect is death, the
following are definite adverse effects:
Altered food consumption
Altered body or organ weight
Altered enzyme or hormone levels, ..etc

Harmful effects
An effect is considered harmful if it causes a functional
damage to an organ, irreversible change in homeostasis or
increased susceptibility to chemical or biological stress
including infectious diseases.
One should consider the degree of alteration from
normality and the relation of the altered property to the
total well-being of the person
In some cases, a person can adapt to the irreversible
alteration and practice normal life

In some cases of immune reactions
leading to allergy:
The first exposure may not cause an adverse effect
of allergy, however, it may sensitize the organism
to respond adversely (badly) to future exposures
even at lower levels

Amount of exposure
The amount of exposure to a chemical that causes
injury varies over a very wide range depending on
the type of chemical and its form (liquid, solid, or
gas)
This can be quantified using the median lethal dose
(LD 50 ) concept or lethal concentration LC 50

Median Lethal Dose (LD 50), mg toxin/kg
body weight
LD 50 is a statistically derived single dose of a
chemical that can be expected to cause the death of
50% of organisms of a given population, under a
defined set of experimental conditions.
LD 50 ‘s s when reported for human beings are
obtained by extrapolation from studies on
mammals, or observations following accidental or
suicidal exposures.

The LD 50 is used to classify and compare toxicity of
chemicals, although it is of limited merits. For example,
the LD 50 classification orally to rats are:
Very toxic
less than 25 mg/kg
Toxic from 25 -199 mg/kg
Harmful from 200 - 2000 mg/kg
However, it is not convincing to label a substance as toxic
because its LD 50 is 199, while labeling another as harmful
since its LD 50 is 200. That is why the LD 50 values need
more refinements.

In addition, when using LD 50 values, there is no
simple relationship between lethality and sub lethal
toxic effects.
In other words also, it is not informative to what is
the minimum dose that can be lethal, and thus no
indication of what can be considered a safe
exposure level.

Toxicity versus Risk
With regards to chemical safety, risk assessment
can be more important than actual toxicity of
chemicals.
Risk can be regarded as the probability that a
substance would impart unacceptable harm or
unacceptable effects to an organ or to ecosystems
upon exposure.

Safety
It is possible to define safety as the practical certainty that
injury will not (high probability) result from exposure to a
hazard under defined conditions.
Practical certainty is a numerically specified low risk (or
socially acceptable risk).
Assessment of risk depends on scientific data, but
acceptability is influenced by social, economic, political
and benefits arising from a chemical or a process.

Uncertainty (safety) factors
A threshold of exposure above which an adverse
effect can occur and below which no such effect is
observed, is obtained from available data.
The threshold of exposure is then divided by a
factor (uncertainty or safety factor) to lower it to a
new value that toxicologists can regard as safe
beyond doubt.

US National Academy of Sciences safe drinking
water committee proposed the following guidelines
for selecting the safety factors, to be used with no
observed effect level (NOEL) data.

Safety Factor Selection:
1. An uncertainty (safety) factor of 10 is used when
valid human data based on chronic exposure is
available
2. An uncertainty (safety) factor of 100 is used
when human data is inconclusive or limited to
acute exposure, but reliable data on animals is
available
3. An uncertainty (safety) factor of 1000 is used
when no human data is available and
experimental animal data is limited

Exposure to potentially toxic substances
Toxins can cause injury when they reach
sensitive parts of an organism at a sufficiently
high concentration.
Exposure can occur through:
1. Skin (dermal or percutaneous) ) Absorption
2. Inhalation
3. Ingestion

Skin absorption
Among the chemicals that are absorbed through the skin
are aniline, hydrogen cyanide, some steroid hormones,
organic mercury compounds, nitrobenzene,
organophosphate compounds and phenol. Some
chemicals, such as phenol or methylmercury chloride, can
be lethal if absorbed from a fairly small area (a few square
centimeters) of skin. If protective clothing is being worn,
it must be remembered that absorption through the skin of
any chemical that gets inside the clothing will be even
faster than through unprotected skin because the chemical
cannot escape and contact is maintained over a longer
time.

Inhalation
Gases and vapors are easily inhaled but inhalation of
particles depends upon their size and shape. The smaller
the particle, the further into the respiratory tract it can go.
Dusts with an effective aerodynamic diameter of between
0.5 and 7 µm m can persist in the alveoli and respiratory
bronchioles after deposition. Peak retention depends upon
the aerodynamic shape but is mainly of those particles
with an effective aerodynamic diameter of between 1 and
2 µm.

Physical irritation by dust particles or fibers can cause very
serious adverse health effects but most effects depend
upon the solids being dissolved. Special consideration
should be given to asbestos fibers which may lodge in the
lung and cause fibrosis and cancer even though they are
mostly insoluble and therefore do not act like classical
toxicants: care should also be taken in assessing possible
harm from man-made made mineral fibers that have similar
properties.
Some insoluble particles such as asbestos, coal dust and
silica dust will readily cause fibrosis of the lung

Ingestion
A chemical may accumulate if absorption exceeds
excretion; this is particularly likely with substances
that combine a fairly high degree of lipid solubility
with chemical stability. Such chemicals are found
in the group of persistent organic pollutants
(POPS), including several organochlorine
pesticides, which are now largely, but not entirely,
banned from use

Divalent lead ions accumulate in bone where they
replace the chemically similar calcium ions. While
in the bone, they cause little harm but when bone
breaks down, or during pregnancy or illness, the
lead ions enter the blood and may poison the
person who has accumulated them or, in the case
of pregnancy, the unborn child.