PRINCIPLES OF TOXICOLOGY

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REFERENCES AND SUGGESTED READING 33 Ballantine, B., and J. B. Sullivan, “Basic principles of toxicology,” in Hazardous Materials Toxicology: Clinical Principles of Environmental Health, J. B. Sullivan and G. R. Krieger, eds., Williams & Wilkins, Baltimore, 1992, pp. 9–23. Beck, B. D., E. J. Calabrese, and P. D. Anderson, “ The use of toxicology in the regulatory process,” in Principles and Methods of Toxicology, 2nd ed., A. W. Hayes, ed., Raven Press, New York, 1989, pp. 1–28. Calabrese, E. J., in Multiple Chemical Interactions, E. J. Calabrese, ed., Lewis Publishers, Chelsea, MI, 1991, pp. 467–544, 585–600. Deschamps, J., and D. Morgan, “Information resources for toxicology,” in General and Applied Toxicology, B. Ballantyne, T. Marrs, and P. Turner, eds., M. Stockton Press, New York, 1993, pp. 217–230. Eaton, D. L., and C. D. Klassen, "Principles of toxicology," in Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed., C. D. Klassen, ed., McGraw-Hill, New York, 1996, pp 13–34. Gallo, M. A., “History and scope of toxicology,” in Casarett and Doull’s Toxicology: The Basic Science of Poisons, 5th ed., C. D. Klassen, ed., McGraw-Hill, New York, 1996, pp. 3–12. Koeman, J. H., “Toxicology: History and scope of the field,” in Toxicology: Principles and Applications, R. J. M. Niesink, J. deVries, and M. A. Hollinger, eds., CRC Press, New York, 1996, pp. 2–15. Musch, A., “ Exposure: Qualitative and quantitative aspects,” in Toxicology: Principles and Applications, R. J. M. Niesink, J. deVries, and M. A. Hollinger, eds., CRC Press, New York, 1996, pp. 16–39. Ottobani, M. A., “How chemicals cause harm,” in The Dose Makes the Poison, M. A. Ottobani, ed., Van Nostrand-Rheinhold, New York, 1991, pp. 19–28. Ottobani, M. A., “Toxiology—a brief history,” in The Dose Makes the Poison, M. A. Ottobani, ed., Van Nostrand-Rheinhold, New York, 1991, pp. 29–38. Ottobani, M. A., “Factors that influence toxicity: How much—how often,” in The Dose Makes the Poison, M. A. Ottobani, ed., Van Nostrand-Rheinhold, New York, 1991, pp. 39–54. Ottobani, M. A., “Other factors that influence toxicity,” in The Dose Makes the Poison, M. A. Ottobani, ed., Van Nostrand-Rheinhold, New York, 1991, pp. 55–68. Rhodes, C., M. Thomas, and J. Athis, “ Principles of testing for acute effects,” in General and Applied Toxicology, B. Ballantyne, T. Marrs, and P. Turner, eds., M. Stockton Press, New York, 1993, pp. 49–88. Sullivan, J. B., and G. R. Krieger, “Introduction to hazardous material toxicology,” in Hazardous Materials Toxicology: Clinical Principles of Environmental Health, J. B. Sullivan and G. R. Krieger, eds., Williams & Wilkins, Baltimore, 1992, pp. 2–8. Vesell, E. S., “Pharmacogenetic differences between humans and laboratory animals: Implications for modeling,” in Human Risk Assessment: The Role of the Animal Selection and Extrapolation, V. M. Roloff, ed., Taylor & Francis, 1987, pp. 229–238. Williams, C. A., H. D. Jones, R. W. Freeman, M. J. Wernke, P. L. Williams, S. M. Roberts, and R. C. James, “The EPC approach to estimating safety from exposure to environmental chemicals,” Regul. Pharmacol. Toxicol. 20: 259–280 (1994). Williams, P. L., “Pentachlorophenol: An assessment of the occupational hazard,” Am. Ind. Hyg. Assoc. J. 43: 799–810 (1982).
34 GENERAL PRINCIPLES OF TOXICOLOGY Answers to Table 1.1 Comparative Acutely Lethal Doses Actual Ranking No. LD50 (mg/kg) Toxic Chemical 1 15,000 PCBs 2 10,000 Alcohol (ethanol) 3 4,000 Table salt—sodium chloride 4 1,500 Ferrous sulfate—an iron supplement 5 1,375 Malathion—pesticide 6 900 Morphine 7 150 Phenobarbital—a sedative 8 142 Tylenol (acetaminophen) 9 2 Strychnine—a rat poison 10 1 Nicotine 11 0.5 Curare—an arrow poison 12 0.001 2,3,7,8-TCDD (dioxin) 13 0.00001 Botulinum toxin (food poison) Adapted from Loomis’s Essentials of Toxicology, Fourth Edition, T.A. Loomis and A.W. Hayes, Academic Press, San Diego, CA, 1996. Answers to Table 1.2 Occupational Exposure Limits: Aspirin and Vegetable Oil Versus Industrial Solvents N Allowable Workplace Exposure Level (mg/m 3 ) Chemical (use) 1 0.1 Iodine 2 5 Aspirin 3 10 Vegetable oil mists (cooking oil) 4 55 1,1,2-Trichloroethane (solvent/degreaser) 5 188 Perchloroethylene (dry-cleaning fluid) 6 170 Toluene (organic solvent) 7 269 Trichloroethylene (solvent/degreaser) 8 590 Tetrahydrofuran (organic solvent) 9 890 Gasoline (fuel) 10 1590 Naphtha (rubber solvent) 11 1910 1,1,1-Trichloroethane (solvent/degreaser) Source: American Conference of Government Industrial Hygienists (ACGIH), 1996.
Page 1 and 2: PRINCIPLES OF TOXICOLOGY
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Page 5 and 6: vi CONTRI BUTORS PAUL J. MIDDENDORF
Page 7 and 8: viii CONTENTS 4 Hematotoxicity: Che
Page 9 and 10: x CONTENTS 12 Mutagenesis and Genet
Page 11 and 12: xii CONTENTS III APPLICATIONS 435 1
Page 13 and 14: PREFACE Purpose of This Book Princi
Page 15 and 16: ACKNOWLEDGMENTS A text of this unde
Page 17 and 18: PART I Conceptual Aspects Principle
Page 19 and 20: 4 GENERAL PRINCIPLES OF TOXICOLOGY
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Page 77 and 78: Figure 3.5 Diagrammatic rendition o
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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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19.4 PETROLEUM HYDROCARBONS: ASSESS
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19.5 RISK ASSESSMENT FOR ARSENIC 48
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19.5 RISK ASSESSMENT FOR ARSENIC 48
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19.6 REEVALUATION OF THE CARCINOGEN
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REFERENCES AND SUGGESTED READING RE
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20 Occupational and Environmental H
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20.1 DEFINITION AND SCOPE OF THE PR
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20.4 HUMAN RESOURCES IMPORTANT TO O
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treatment, or medical removal from
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Academic practices welcome complica
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Occupational and environmental medi
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512 EPIDEMIOLOGIC ISSUES IN OCCUPAT
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22 Controlling Occupational and Env
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22.2 EXPOSURE LIMITS 525 The TLVs
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modified “reference doses” to r
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observation process, followed by re
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• Hazard-specific training to ens
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22.3 PROGRAM MANAGEMENT 533 Conside
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Figure 22.1 22.3 PROGRAM MANAGEMENT
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fundamental viability of the work p
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Figure 22.2. 22.3 PROGRAM MANAGEMEN
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• Physical assessment and fit tes
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The study was designed to minimize
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TABLE 22.3 Margins of Safety at For
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top, and numerous slots with smalle
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TABLE 22.5 Comparison of Time-Weigh
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• Housing or building code violat
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• Environmental exposure limits,
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GLOSSARY Glossary absorption The mo
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GLOSSARY 557 antipyretic An agent t
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GLOSSARY 559 chloracne An acne-like
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GLOSSARY 561 eczema A superficial i
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GLOSSARY 563 hemolytic anemia Anemi
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GLOSSARY 565 lipoprotein Any of a g
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GLOSSARY 567 necrosis Death of one
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pernicious anemia The progressive,
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GLOSSARY 571 cells have both endoth
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GLOSSARY 573 tolerance The ability
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576 INDEX Allergic reaction (contin
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578 INDEX Biotransformation (contin
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580 INDEX Children’s health statu
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582 INDEX Diet and nutrition (conti
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584 INDEX Estrogens: endocrine disr
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586 INDEX Hair, toxic agent excreti
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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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PRINCIPLES OF TOXICOLOGY

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