PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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CONTENTSxi15.4 Herbicides 35615.5 Fungicides 35815.6 Rodenticides 36015.7 Fumigants 36115.8 Summary 362References and Suggested Reading 36316 Properties and Effects of Organic Solvents 367Christopher M. Teaf16.1 Exposure Potential 36716.2 Basic Principles 36816.3 Toxic Properties of Representative Aliphatic Organic Solvents 37716.4 Toxic Properties of Representative Alicyclic Solvents 37816.5 Toxic Properties of Representative Aromatic Hydrocarbon Solvents 37916.6 Toxic Properties of Representative Alcohols 38216.7 Toxic Properties of Representative Phenols 38416.8 Toxic Properties of Representative Aldehydes 38516.9 Toxic Properties of Representative Ketones 38816.10 Toxic Properties of Representative Carboxylic Acids 38916.11 Toxic Properties of Representative Esters 39016.12 Toxic Properties of Representative Ethers 39016.13 Toxic Properties of Representative Halogenated Alkanes 39116.14 Toxic Properties of Representative Nitrogen-Substituted Solvents 39816.15 Toxic Properties of Representative Aliphatic and Aromatic NitroCompounds 40216.16 Toxic Properties of Representative Nitriles (Alkyl Cyanides) 40416.17 Toxic Properties of the Pyridine Series 40516.18 Sulfur-Substituted Solvents 40516.19 Summary 407References and Suggested Reading 40717 Properties and Effects of Natural Toxins and Venoms 409William R. Kem17.1 Poisons, Toxins, and Venoms 40917.2 Molecular and Functional Diversity of Natural Toxins and Venoms 41017.3 Natural Roles of Toxins and Venoms 41117.4 Major Sites and Mechanisms of Toxic Action 41117.5 Toxins in Unicellular Organisms 41517.6 Toxins of Higher Plants 41717.7 Animal Venoms and Toxins 42317.8 Toxin and Venom Therapy 43017.9 Summary 432Acknowledgments 432References and Suggested Reading 432
xiiCONTENTSIII APPLICATIONS 43518 Risk Assessment 437Robert C. James, D. Alan Warren, Christine Halmes, andStephen M. Roberts18.1 Risk Assessment Basics 43718.3 Exposure Assessment: Exposure Pathways and Resulting Dosages 44518.4 Dose–Response Assessment 44918.5 Risk Characterization 46018.6 Probabilistic Versus Deterministic Risk Assessments 46218.7 Evaluating Risk from Chemical Mixtures 46418.8 Comparative Risk Analysis 46818.9 Risk Communication 47218.10 Summary 474References and Suggested Reading 47519 Example of Risk Assessment Applications 479Alan C. Nye, Glenn C. Millner, Jay Gandy, and Phillip T. Goad19.1. Tiered Approach to Risk Assessment 47919.2. Risk Assessment Examples 48019.3. Lead Exposure and Women of Child-bearing Age 48119.4. Petroleum Hydrocarbons: Assessing Exposure and Risk to Mixtures 48319.5. Risk Assessment for Arsenic 48619.6. Reevaluation of the Carcinogenic Risks of Inhaled Antimony Trioxide 49019.7. Summary 496References and Suggested Reading 49720 Occupational and Environmental Health 499Fredric Gerr, Edward Galaid, and Howard Frumkin20.1 Definition and Scope of the Problem 49920.2 Characteristics of Occupational Illness 50220.3 Goals of Occupational and Environmental Medicine 50220.4 Human Resources Important to Occupational Health Practice 50320.5 Activities of the Occupational Health Provider 50320.6 Ethical Considerations 50720.7 Summary and Conclusion 508References and Suggested Reading 50921 Epidemiologic Issues in Occupational and Environmental Health 511Lora E. Fleming and Judy A. Bean21.1 A Brief History of Epidemiology 51121.2 Epidemiologic Causation 51221.3 Types of Epidemiologic Studies: Advantages and Disadvantages 51321.4 Exposure Issues 51421.5 Disease and Human Health Effects Issues 515
Page 4 and 5: CONTRIBUTORSLOUIS ADAMS, PH.D. Prof
Page 6 and 7: CONTENTSPREFACExvACKNOWLEDGMENTSxvi
Page 8 and 9: CONTENTSix7.3 Agents that Act on th
Page 12 and 13: CONTENTSxiii21.6 Population Issues
Page 14 and 15: xviPREFACE• The approach is scien
Page 16 and 17: PRINCIPLES OF TOXICOLOGY
Page 18 and 19: 1 General Principles of ToxicologyG
Page 20 and 21: 1.2 WHAT TOXICOLOGISTS STUDY 5Delay
Page 22 and 23: 1.3 THE IMPORTANCE OF DOSE AND THE
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Page 34 and 35: 1.5 AVOIDING INCORRECT CONCLUSIONS
Page 36 and 37: 1.6 FACTORS INFLUENCING DOSE-RESPON
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Page 41 and 42: 26 GENERAL PRINCIPLES OF TOXICOLOGY
Page 51 and 52: 36 ABSORPTION, DISTRIBUTION, AND EL
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2.4 DISPOSITION: DISTRIBUTION AND E
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2.5 SUMMARY 53the transfer from liv
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REFERENCES AND SUGGESTED READING 55
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58 BIOTRANSFORMATION: A BALANCE BET
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60Figure 3.3 Xenobiotic metabolism
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TABLE 3.4 Important Cytochrome P450
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88 HEMATOTOXICITY: CHEMICALLY INDUC
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100 HEMATOTOXICITY: CHEMICALLY INDU
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5 Hepatotoxicity: Toxic Effects on
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5.1 THE PHYSIOLOGIC AND MORPHOLOGIC
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5.1 THE PHYSIOLOGIC AND MORPHOLOGIC
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5.2 TYPES OF LIVER INJURY 117cause
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5.2 TYPES OF LIVER INJURY 119Exampl
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5.2 TYPES OF LIVER INJURY 121TABLE
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5.2 TYPES OF LIVER INJURY 123to pro
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5.3 EVALUATION OF LIVER INJURY 125f
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6 Nephrotoxicity: Toxic Responses o
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6.1 BASIC KIDNEY STRUCTURES AND FUN
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6.1 BASIC KIDNEY STRUCTURES AND FUN
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6.2 FUNCTIONAL MEASUREMENTS TO EVAL
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6.3 ADVERSE EFFECTS OF CHEMICALS ON
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146 NEUROTOXICITY: TOXIC RESPONSES
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8 Dermal and Ocular Toxicology: Tox
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8.2 FUNCTIONS 159corneum is the pri
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8.3 CONTACT DERMATITIS 161TABLE 8.2
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8.3 CONTACT DERMATITIS 163mucous me
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8.3 CONTACT DERMATITIS 165light to
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8.4 SUMMARY 167The structure of the
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9 Pulmonotoxicity: Toxic Effects in
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9.1 LUNG ANATOMY AND PHYSIOLOGY 171
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9.2 MECHANISMS OF INDUSTRIALLY RELA
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9.2 MECHANISMS OF INDUSTRIALLY RELA
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9.3 SUMMARY 185Industrially Related
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190 IMMUNOTOXICITY: TOXIC EFFECTS O
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11 Reproductive ToxicologyREPRODUCT
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11.1 MALE REPRODUCTIVE TOXICOLOGY 2
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11.2 FEMALE REPRODUCTIVE TOXICOLOGY
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11.3 DEVELOPMENTAL TOXICOLOGY 225de
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11.3 DEVELOPMENTAL TOXICOLOGY 227af
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11.3 DEVELOPMENTAL TOXICOLOGY 229ri
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11.3 DEVELOPMENTAL TOXICOLOGY 231to
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11.4 CURRENT RESEARCH CONCERNS 233T
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11.4 CURRENT RESEARCH CONCERNS 235
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12 Mutagenesis and Genetic Toxicolo
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12.2 GENETIC FUNDAMENTALS AND EVALU
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TABLE 12-1. Correspondence of the G
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12.3 NONMAMMALIAN MUTAGENICITY TEST
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12.4 MAMMALIAN MUTAGENICITY TESTS 2
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12.4 MAMMALIAN MUTAGENICITY TESTS 2
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12.5 OCCUPATIONAL SIGNIFICANCE OF M
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REFERENCES CITED AND SUGGESTED READ
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13 Chemical CarcinogenesisCHEMICAL
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13.1 THE TERMINOLOGY OF CANCER 267H
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13.3 CARCINOGENESIS BY CHEMICALS 26
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Figure 13.1 Schematic diagram of th
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Figure 13.4 Metabolic activation of
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13.4 MOLECULAR ASPECTS OF CARCINOGE
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Figure 13.7 DNA damage leads to p53
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13.5 TESTING CHEMICALS FOR CARCINOG
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13.5 TESTING CHEMICALS FOR CARCINOG
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13.6 INTERPRETATION ISSUES RAISED B
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13.7 EMPIRICAL MEASURES OF RELIABIL
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13.8 OCCUPATIONAL CARCINOGENS 301TA
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13.8 OCCUPATIONAL CARCINOGENS 303TA
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13.9 CANCER AND OUR ENVIRONMENT 305
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13.10 CANCER TRENDS AND THEIR IMPAC
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13.11 SUMMARY 321from non-Hodgkin
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14 Properties and Effects of Metals
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14.2 SPECIATION OF METALS 327Most o
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14.3 PHARMACOKINETICS OF METALS 329
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14.4 TOXICITY OF METALS 331reflex i
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14.4 TOXICITY OF METALS 333Several
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14.5 SOURCES OF METAL EXPOSURE 335H
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14.6 TOXICOLOGY OF SELECTED METALS
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14.7 SUMMARY 343Zinc is required fo
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15 Properties and Effects of Pestic
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15.1 ORGANOPHOSPHATE AND CARBAMATE
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15.3 INSECTICIDES OF BIOLOGICAL ORI
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15.3 INSECTICIDES OF BIOLOGICAL ORI
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15.4 HERBICIDES 357ClClO CH 2 C OOH
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15.5 FUNGICIDES 359temperatures as
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15.7 FUMIGANTS 361thallium sulfate-
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16 Properties and Effects of Organi
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TABLE 16.1 Physicochemical Properti
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16.2 BASIC PRINCIPLES 371TABLE 16.2
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16.2 BASIC PRINCIPLES 373Once absor
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16.2 BASIC PRINCIPLES 375the additi
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16.3 TOXIC PROPERTIES OF REPRESENTA
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16.10 TOXIC PROPERTIES OF REPRESENT
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16.15 TOXIC PROPERTIES 403observed
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16.18 SULFUR-SUBSTITUTED SOLVENTS 4
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17 Properties and Effects of Natura
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17.3 NATURAL ROLES OF TOXINS AND VE
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17.4 MAJOR SITES AND MECHANISMS OF
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17.5 TOXINS IN UNICELLULAR ORGANISM
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17.6 TOXINS OF HIGHER PLANTS 417phy
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17.6 TOXINS OF HIGHER PLANTS 419whi
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17.6 TOXINS OF HIGHER PLANTS 421TAB
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17.7 ANIMAL VENOMS AND TOXINS 423of
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17.7 ANIMAL VENOMS AND TOXINS 425ac
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17.7 ANIMAL VENOMS AND TOXINS 427co
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17.7 ANIMAL VENOMS AND TOXINS 429Fi
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17.8 TOXIN AND VENOM THERAPY 431One
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18 Risk AssessmentRISK ASSESSMENTRO
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18.1 RISK ASSESSMENT BASICS 439Step
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18.1 RISK ASSESSMENT BASICS 441For
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18.2 HAZARD IDENTIFICATION 443chemi
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18.3 EXPOSURE ASSESSMENT: EXPOSURE
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18.3 EXPOSURE ASSESSMENT: EXPOSURE
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18.4 DOSE-RESPONSE ASSESSMENT 449Af
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18.4 DOSE-RESPONSE ASSESSMENT 451me
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18.4 DOSE-RESPONSE ASSESSMENT 453Fi
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18.4 DOSE-RESPONSE ASSESSMENT 455No
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18.4 DOSE-RESPONSE ASSESSMENT 457Fi
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18.4 DOSE-RESPONSE ASSESSMENT 459Ge
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18.5 RISK CHARACTERIZATION 461likel
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18.6 PROBABILISTIC VERSUS DETERMINI
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18.7 EVALUATING RISK FROM CHEMICAL
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18.7 EVALUATING RISK FROM CHEMICAL
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18.8 COMPARATIVE RISK ANALYSIS 469r
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18.8 COMPARATIVE RISK ANALYSIS 471T
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18.9 RISK COMMUNICATION 473TABLE 18
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480 EXAMPLE OF RISK ASSESSMENT APPL
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500 OCCUPATIONAL AND ENVIRONMENTAL
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21 Epidemiologic Issues inOccupatio
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21.3 TYPES OF EPIDEMIOLOGIC STUDIES
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21.5 DISEASE AND HUMAN HEALTH EFFEC
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21.8 MEASUREMENT OF ASSOCIATION OR
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21.9 BIAS 519increased or decreased
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524 CONTROLLING OCCUPATIONAL AND EN
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556 GLOSSARYaliphatic Organic compo
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558 GLOSSARYbenign tumor A new tiss
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560 GLOSSARYcytokinesis The divisio
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562 GLOSSARYerythropoietic stimulat
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564 GLOSSARYinhalation route The mo
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566 GLOSSARYmitochondria Small sphe
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568 GLOSSARYoral route The entry of
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570 GLOSSARYporphyrin Any of a grou
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572 GLOSSARYspirometry The measurem
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INDEXAbsorbed dose, defined, 4Absor
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INDEX 577Area under the tissue conc
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INDEX 579animal studies, 297cellula
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INDEX 581speciation of, 327-328Corp
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INDEX 583organ-specific activities,
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INDEX 585Follicle-stimulating hormo
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INDEX 587fatty liver, 120-122hepato
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INDEX 589Isoniazid metabolism, path
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INDEX 591Mechanistic toxicology, as
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INDEX 593Nephropathy:defined 130nep
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INDEX 595neurobehavioral sequelae,
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INDEX 597Probability density functi
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INDEX 599Rodenticides, 360.-361sodi
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INDEX 601Safe Human Dose (SHD) appr
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INDEX 603drug metabolism factors, 7
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