PRINCIPLES OF TOXICOLOGY

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538 CONTROLLING OCCUPATIONAL AND ENVIRONMENTAL HEALTH HAZARDS U.S. Air Force has been conducting research on the use of robotic lasers to strip paint from its aircraft to replace the current method of using methylene chloride–based chemical strippers. In the late 1990s, some legislation was passed at the state level requiring industry to reduce the use of toxic substances on a certain schedule. Whether these targets are realistic remains to be seen. However, these initiatives could radically alter the prevailing conception of what is and is not feasible in the development of new processes and new substitutes. Source Isolation Source isolation can effectively prevent exposure, and thus reduce the hazard. A potential hazard still remains, however, since a leak can develop and result in exposure. The Union Carbide incident at Bhopal, India in 1993 may be the best-known example. Backup alarm systems warning of a breech in the isolating mechanism are usually specified for this type of control measure, and emergency response procedures must be established. Specific requirements for process safety management for processes which use highly hazardous chemicals have been established by OSHA. Enclosures with their own dedicated exhaust ventilation systems are another type of source enclosure. In poultry hatcheries, formaldehyde is used to disinfect the eggs, which are isolated inside an incubation chamber. Planning must include specification of those work processes that will require entry into the enclosure, and the types of protective measures, such as the type of respirator to be used, and how much ventilation of the enclosure will be needed after production has ceased before entry can be safely completed. Maintenance activities and emergency-response operations often require entry into such enclosure systems. In the case of the hatchery, at least 60 min of purge time at 20 air changes per hour or greater must be allowed before a worker enters the booth. To provide adequate mixing within the booth, velocities through air inlet doors should be at least 500 feet per minute (fpm), and velocities through large access doors should be at least 100 fpm. Worker Isolation If the toxic substance cannot be isolated, then perhaps the worker can be. For example, it is not feasible to enclose a large railcar coal dumping station at a large power plant. However, a small operator’s booth, with its own filtered source of fresh, tempered air, is certainly feasible. Again, plans should include provisions for emergency exit from the enclosure into the hazardous atmosphere. Many worker isolation enclosures fail because they do not provide the necessary comfort. If heated or cooled fresh air is not supplied to the extent necessary, the employee is likely to open the door, resulting in potential overexposure. These provisions are sometimes regarded as an unnecessary “creature comfort” expense. In reality, they need to be viewed as an integral part of the control mechanism, for without it, the control fails. Even if employees are trained in the hazards of compromising the enclosure’s integrity, on hot summer days the worker may view the immediate problem of baking inside the enclosure as worse than being exposed to an undetectable toxicant. This is a flaw in the design, not “human nature.” Local Exhaust and Dilution Ventilation If it is not feasible to substitute for the chemical, modify the process, or prevent the release of the air contaminant into the workers’ environment, then local exhaust or dilution ventilation will be needed. Of the two, local exhaust ventilation is more desirable, because more complete capture of the contaminant is possible in most cases and smaller amounts of air will need to be moved, resulting in energy cost savings. Local exhaust ventilation systems consist of a hood, ductwork, a fan, a pollution-control device, and an exhaust stack. Hoods can be of the external or internal variety. The external hood is designed to capture air contaminants released some distance in front of the hood, while the internal hood controls the contaminant inside some type of partial enclosure. Figure 22.2 shows a welding fume extractor and a laboratory hood, illustrating the differences between the two types of hood. Generally, a greater degree of control can be exerted by an internal hood, since the chances of cross-drafts and other sources of turbulence are less. However, even the best designed laboratory hood will exhibit some degree of leakage. Training of employees in the proper use of ventilating equipment is crucial. Laboratory workers need to understand the consequences of placing too many bottles inside their hoods or not placing the
Figure 22.2. 22.3 PROGRAM MANAGEMENT 539
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PRINCIPLES OF TOXICOLOGY
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This book is printed on acid-free p
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vi CONTRI BUTORS PAUL J. MIDDENDORF
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viii CONTENTS 4 Hematotoxicity: Che
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x CONTENTS 12 Mutagenesis and Genet
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xii CONTENTS III APPLICATIONS 435 1
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PREFACE Purpose of This Book Princi
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ACKNOWLEDGMENTS A text of this unde
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PART I Conceptual Aspects Principle
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4 GENERAL PRINCIPLES OF TOXICOLOGY
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36 ABSORPTION, DISTRIBUTION, AND EL
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3 Biotransformation: A Balance betw
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BIOTRANSFORMATION: A BALANCE BETWEE
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BIOTRANSFORMATION: A BALANCE BETWEE
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Figure 3.5 Diagrammatic rendition o
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3.2 BIOTRANSFORMATION REACTIONS The
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TABLE 3.4 Important Cytochrome P450
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Figure 3.8 Cytochrome P450-catalyze
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oth of which are suitable for conju
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TABLE 3.6 Changes in Rat Hepatic Dr
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3.2 BIOTRANSFORMATION REACTIONS 75
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TABLE 3.7 Induction of Xenobiotic-M
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3.2 BIOTRANSFORMATION REACTIONS 79
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pyridoxal phosphate depletion by th
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Biotransformation: A Balance betwee
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een shown to be responsible for the
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4 Hematotoxicity: Chemically Induce
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Figure 4.1 Formation of blood. Matu
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TABLE 4.2 Leukemias and Lymphomas 4
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4.3 THE MYELOID SERIES 93 to contra
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function and response to stimuli, (
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Hypoxia can result from a variety o
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4.7 INORGANIC NITRATES/NITRITES AND
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Exposure to aromatic amines can be
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4.10 BONE MARROW SUPPRESSION AND LE
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4.12 TOXICITIES THAT INDIRECTLY INV
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4.15 ANTIDOTES FOR HYDROGEN SULFIDE
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REFERENCES AND SUGGESTED READING 10
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112 HEPATOTOXICITY: TOXIC EFFECTS O
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130 NEPHROTOXICITY: TOXIC RESPONSES
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7 Neurotoxicity: Toxic Responses of
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ions moving out of the cell brings
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an effect seen with some neurotoxic
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7.4 INTERACTIONS OF INDUSTRIAL CHEM
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• A study of the patient’s hist
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• Although much of the damage whi
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158 DERMAL AND OCULAR TOXICOLOGY Fi
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160 DERMAL AND OCULAR TOXICOLOGY P4
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162 DERMAL AND OCULAR TOXICOLOGY ca
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164 DERMAL AND OCULAR TOXICOLOGY ke
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166 DERMAL AND OCULAR TOXICOLOGY Fi
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168 DERMAL AND OCULAR TOXICOLOGY
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170 PULMONOTOXICITY: TOXIC EFFECTS
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10 Immunotoxicity: Toxic Effects on
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10.2 BIOLOGY OF THE IMMUNE RESPONSE
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10.2 BIOLOGY OF THE IMMUNE RESPONSE
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certain situations immunosuppressio
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10.5 TESTS FOR DETECTING IMMUNOTOXI
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10.6 SPECIFIC CHEMICALS THAT ADVERS
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10.6 SPECIFIC CHEMICALS THAT ADVERS
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animal origin have also been shown
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The mainstay of treatment of multip
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PART II Specific Areas of Concern P
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210 REPRODUCTIVE TOXICOLOGY continu
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212 REPRODUCTIVE TOXICOLOGY Underst
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214 REPRODUCTIVE TOXICOLOGY spermat
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216 REPRODUCTIVE TOXICOLOGY gonadot
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218 REPRODUCTIVE TOXICOLOGY TABLE 1
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Figure 11.3 Cycle of follicular dev
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222 REPRODUCTIVE TOXICOLOGY Figure
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224 REPRODUCTIVE TOXICOLOGY TABLE 1
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226 Figure 11.5 Developmental tree
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228 REPRODUCTIVE TOXICOLOGY is clea
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230 REPRODUCTIVE TOXICOLOGY genital
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232 REPRODUCTIVE TOXICOLOGY to occu
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234 REPRODUCTIVE TOXICOLOGY these r
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236 REPRODUCTIVE TOXICOLOGY Two imp
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238 REPRODUCTIVE TOXICOLOGY Sundara
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240 MUTAGENESIS AND GENETIC TOXICOL
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248 Figure 12.5 Example of DNA addu
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TABLE 12-3 NTP and Gene-Tox Evaluat
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266 CHEMICAL CARCINOGENESIS 13.1 TH
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268 CHEMICAL CARCINOGENESIS TABLE 1
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270 CHEMICAL CARCINOGENESIS researc
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272 CHEMICAL CARCINOGENESIS Figure
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276
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280 CHEMICAL CARCINOGENESIS 13.4 MO
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286 CHEMICAL CARCINOGENESIS make a
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288 Figure 13.8 A genetic model of
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290 CHEMICAL CARCINOGENESIS Increas
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292 CHEMICAL CARCINOGENESIS may be
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294 CHEMICAL CARCINOGENESIS • The
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296 CHEMICAL CARCINOGENESIS evaluat
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298 CHEMICAL CARCINOGENESIS In rats
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302 CHEMICAL CARCINOGENESIS with ex
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316 CHEMICAL CARCINOGENESIS similar
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324 CHEMICAL CARCINOGENESIS Knudson
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326 PROPERTIES AND EFFECTS OF METAL
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332 TABLE 14.2 Target Organ Toxicit
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346 PROPERTIES AND EFFECTS OF PESTI
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368 PROPERTIES AND EFFECTS OF ORGAN
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370 TABLE 16.1 (Continued) Water So
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410 PROPERTIES AND EFFECTS OF NATUR
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PART III Applications Principles of
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438 RISK ASSESSMENT 18.1 RISK ASSES
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440 RISK ASSESSMENT control populat
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442 RISK ASSESSMENT there are some
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444 RISK ASSESSMENT • It identifi
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446 RISK ASSESSMENT chemical poses
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448 RISK ASSESSMENT • Estimating
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450 RISK ASSESSMENT Figure 18.3 Est
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452 RISK ASSESSMENT • As discusse
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454 RISK ASSESSMENT divided by a de
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456 RISK ASSESSMENT Because low-dos
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458 RISK ASSESSMENT TABLE 18.1 Expe
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460 RISK ASSESSMENT leading to impo
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462 RISK ASSESSMENT characterizatio
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464 RISK ASSESSMENT Figure 18.7 Sim
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466 RISK ASSESSMENT The RPF values
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468 RISK ASSESSMENT producing the e
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470 RISK ASSESSMENT TABLE 18.4b Can
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472 RISK ASSESSMENT TABLE 18.7 Acti
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474 RISK ASSESSMENT A second reason
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476 RISK ASSESSMENT Barnard, R. C.,
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19 Example of Risk Assessment Appli
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19.3 LEAD EXPOSURE AND WOMEN OF CHI
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19.4 PETROLEUM HYDROCARBONS: ASSESS
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Page 497 and 498: 19.6 REEVALUATION OF THE CARCINOGEN
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Page 507 and 508: 20.1 DEFINITION AND SCOPE OF THE PR
Page 509 and 510: 20.4 HUMAN RESOURCES IMPORTANT TO O
Page 511 and 512: treatment, or medical removal from
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Page 529 and 530: 22.2 EXPOSURE LIMITS 525 The TLVs
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Page 537 and 538: 22.3 PROGRAM MANAGEMENT 533 Conside
Page 539 and 540: Figure 22.1 22.3 PROGRAM MANAGEMENT
Page 541: fundamental viability of the work p
Page 545 and 546: • Physical assessment and fit tes
Page 547 and 548: The study was designed to minimize
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Page 559 and 560: GLOSSARY Glossary absorption The mo
Page 561 and 562: GLOSSARY 557 antipyretic An agent t
Page 563 and 564: GLOSSARY 559 chloracne An acne-like
Page 565 and 566: GLOSSARY 561 eczema A superficial i
Page 567 and 568: GLOSSARY 563 hemolytic anemia Anemi
Page 569 and 570: GLOSSARY 565 lipoprotein Any of a g
Page 571 and 572: GLOSSARY 567 necrosis Death of one
Page 573 and 574: pernicious anemia The progressive,
Page 575 and 576: GLOSSARY 571 cells have both endoth
Page 577 and 578: GLOSSARY 573 tolerance The ability
Page 579 and 580: 576 INDEX Allergic reaction (contin
Page 581 and 582: 578 INDEX Biotransformation (contin
Page 583 and 584: 580 INDEX Children’s health statu
Page 585 and 586: 582 INDEX Diet and nutrition (conti
Page 587 and 588: 584 INDEX Estrogens: endocrine disr
Page 589 and 590: 586 INDEX Hair, toxic agent excreti
Page 591 and 592: 588 INDEX hnmunoglobulins: autoimmu
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590 INDEX Loop of Henle, structure
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592 INDEX Mixed exposure patterns,
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594 INDEX Nutritional deficiencies,
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596 INDEX Pesticides (continued) Pe
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598 INDEX Relative potency factor (
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600 INDEX Solvents (continued) phys
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602 INDEX Tumorigenesis (continued)
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