PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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INDEXAbsorbed dose, defined, 4Absorption mechanisms:in human body, 35-36metals pharmacokinetics, 328organophosphateicarbamate pesticides, 347--348solvent exposure, 3722373toxic agents, 4145gastrointestinal tract, 4143lungs, 43345skin, 43Acceptable ambient-air level (AAAL), environmentalexposure guidelines with, 3 1-32Acetaldehyde, toxicology, 387-388Acetone, toxicology, 3899390Acetophone, toxicology, 389Acetylation, biotransformation, 74Acetylcholine (ACh):neurotransmitter activity, 148-149reptile and amphibian venom toxicology, 424425synaptic neurotoxicity, 15 1Acetylcholinesterase (AChE):neurotransmitter activity, 148-149organophosphateicarbamate pesticides, 347organophosphate-induced delayed neuropathy(OPIDN), 350synaptic neurotoxicity, 15 1Acid anhydride, immunotoxicity, 203Acneiform dermatoses, dermal toxicity, 163-164Acquired immunity, immunotoxicity, 190Acrolein, toxicology, 386, 388Activation, xenobiotic metabolism, enzyme activity,15Active transport, toxic agents, 40Acute accidental poisoning, toxicity data in studiesof, 13Acute exposure:defined 4herbicides, 356metals toxicity, 33 1organochlorine insectides, 353organophosphate/carbamate pesticides, 348-349Acute myelogenous leukemia (AML), benzeneexposure, 103-104Acute renal failure (ARF), nephrotoxicity and, 137Acute toxicity:defined, 4errors in measurement of, 20relative ranking system for, 19-20Acute transforming retroviruses, oncogenes, 280Adenomas:classification, 267-268hepatoxicity and 123Administration routes of carcinogens, carcinogenicitystudies, 2955296Administrative controls:carbon dioxide exposure studies, 549control technologies for hazardous materials, 540Adverse effects, dose-response data and, 27-28Aerosols:metals as, 329pulmonotoxicity and absorption of, 174-175Aflatoxins, sources of, 419Age characteristics:arsenic risk assessment studies, 489490dose-response data, 23-24xenobiotic metabolism, 82Aggregation of disease, epidemiologic studies, 520“Aging” pesticides, absorption and metabolism, 348Agonists, natural venoms and toxin neurotoxicity,411413Air exposure measurements:antimony carcinogenicity risk studies, 495496occupational health hazards control, samplingtechniques, 534-536Air pollutant gases, pulmonotoxicity, 180Alcohol. See also Ethanoltoxicology, 382-384R-OH, 382-383simple alcohols, 383-384Aldehydes, toxicology, 385-388Alicyclic solvents, toxicity, 378-379Aliphatic organic solvents:toxicity, 377-378,402404toxicology, 398402Alkaloidal toxins:in flowering plants, 421in mushrooms, 418419Alkanes:halogenated alkanes, toxicology, 391-397toxicity, 377-378Alkylating agents:carcinogenicity, 274genetic toxicity and 247,249Alkylbenzenes, toxicology of, 380-381Alkyl cyanides, toxicology, 404405Allergens, allergic contact dermatitis, 162Allergic reaction:contact dermatitis, 161-162Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,Robert C. James, and Stephen M. Roberts.ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.575
576 INDEXAllergic reaction (continued)defined 5hymenoptera toxins, 427immunotoxicity, 194metals exposure, dermal contact, 330pulmonotoxicity and respiratory response, 184occupation-related disorders, 184Allowable daily intake (ADI) measurement, riskassessment studies, 45 1454Alveocapillary membrane complex, pulmonotoxicity,gas/vapor exposure, 1788179Amatoxins, toxicology, 417-418Amebic dysentery, natural toxins and, 416417Ames assay:carcinogenicity, 273mutagenicity testing with, 252Amine compounds:relative base strength, 399relative toxicity, 399toxicology, 3988402Aminita mushrooms, toxicology, 417418Amino acid conjugation, biotransformation, 74Amino acids, genetic toxicology and, 242-243Aminoazo dyes, carcinogenicity, 274y-Aminobutyric acid (GABA), neurotransmitterinhibition, 15 1Aminopterin, developmental toxicology of, 230Aminotransferase activities, hepatoxicity andmeasurement of, 127Ammonia, aquatic toxicity interactions, 25Amphibian venoms, toxicology, 423425Analytical observational studies, characteristics of,514Anaphylaactic-type reaction, immunotoxicity and194Anaplasia, defined, 266Androgens:developmental toxicology of, 230male reproductive toxicology and, 2 17Anemia:classification of, 92hypoxia and, 97lead poisoning and 108red blood cell (RBC) development and, 91-92Aneuploidy, chromosomal aberrations and, 250Aniline, toxicology, 400402Animal species/strain:carcinogenicity studies:human differences and, 2977299reliability of extrapolation, 2999301xenobiotic metabolism, enzyme variations, 79981Animal studies:antimony carcinogenicity risks, rodent studies,491494carcinogenic activity, 2899299human anatomic differences, 297-298human cellular and biochemical differences,298.-299human physiologic differences, 298relevant animal models, 297data problems in, 14extrapolation to human exposure, 28-33carcinogenicity studies, reliability in, 299-301environmental exposure guidelines, 31-32exposure routes, 29-3 1risk assessment studies, 443445safe human dose (SHD) approach, 29immunotoxicity assessment, 197-I 99limits of, 21-22Animal venoms and toxins:arthropod toxins and venoms, 426427coelentrate (cnidarian) venoms, 428429fish venoms and toxins, 425426mollusc venoms and toxins, 427428reptiles and amphibians, 423425toxic marine invertebrates, 429430Annelida, venom toxicology in, 430Anoxia:neurotoxicity and, 150-I 5 1red blood cell impairment and, 96697Antagonism, dose-response data and, 24-26Anthropogenic sources, metals exposure from,334-335Antibodies, immunotoxicity, 1922193Anticholinesterase agents, synaptic neurotoxicity,151Anticipation of hazard effects, occupational healthhazards control and, 53 l-532Anticoagulants:clotting factor carboxylation and, 108developmental toxicology of, 230as rodenticides, 360Anticonvulsive agents, developmental toxicology and229Antigen presenting cells (APC):allergic contact dermatitis, 161-162immunotoxicity, 190-191macrophages as, 93-94Antigens, immunotoxicity, 190Antimony, carcinogenic risk assessment, 490496air and soil exposure equations, 495496human studies, 491putative mechanisms for, 4933494rodent studies, 491493short-term genetic toxicity studies, 493weight of evidence characterization, 494496Anti-neoplastic agents. See Chemotherapeutic agentsAntivenin therapy:horse antivenins, 423immunotherapy techniques, 43043 1pharmacokinetics, 43 1reptile and amphibian venoms, 425Apamin, in bee venom, 427Apoptosis:carcinogenesis and 285-289hepatocellular degeneration and death, 117, 119Applied dose, defined, 4Applied toxicology, as research discipline, 6
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CONTRIBUTORSLOUIS ADAMS, PH.D. Prof
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CONTENTSPREFACExvACKNOWLEDGMENTSxvi
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CONTENTSix7.3 Agents that Act on th
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CONTENTSxi15.4 Herbicides 35615.5 F
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CONTENTSxiii21.6 Population Issues
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xviPREFACE• The approach is scien
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PRINCIPLES OF TOXICOLOGY
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1 General Principles of ToxicologyG
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1.2 WHAT TOXICOLOGISTS STUDY 5Delay
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1.3 THE IMPORTANCE OF DOSE AND THE
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1.4 HOW DOSE-RESPONSE DATA CAN BE U
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1.5 AVOIDING INCORRECT CONCLUSIONS
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1.6 FACTORS INFLUENCING DOSE-RESPON
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1.6 FACTORS INFLUENCING DOSE-RESPON
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26 GENERAL PRINCIPLES OF TOXICOLOGY
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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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Page 528 and 529: 524 CONTROLLING OCCUPATIONAL AND EN
Page 560 and 561: 556 GLOSSARYaliphatic Organic compo
Page 562 and 563: 558 GLOSSARYbenign tumor A new tiss
Page 564 and 565: 560 GLOSSARYcytokinesis The divisio
Page 566 and 567: 562 GLOSSARYerythropoietic stimulat
Page 568 and 569: 564 GLOSSARYinhalation route The mo
Page 570 and 571: 566 GLOSSARYmitochondria Small sphe
Page 572 and 573: 568 GLOSSARYoral route The entry of
Page 574 and 575: 570 GLOSSARYporphyrin Any of a grou
Page 576 and 577: 572 GLOSSARYspirometry The measurem
Page 580 and 581: INDEX 577Area under the tissue conc
Page 582 and 583: INDEX 579animal studies, 297cellula
Page 584 and 585: INDEX 581speciation of, 327-328Corp
Page 586 and 587: INDEX 583organ-specific activities,
Page 588 and 589: INDEX 585Follicle-stimulating hormo
Page 590 and 591: INDEX 587fatty liver, 120-122hepato
Page 592 and 593: INDEX 589Isoniazid metabolism, path
Page 594 and 595: INDEX 591Mechanistic toxicology, as
Page 596 and 597: INDEX 593Nephropathy:defined 130nep
Page 598 and 599: INDEX 595neurobehavioral sequelae,
Page 600 and 601: INDEX 597Probability density functi
Page 602 and 603: INDEX 599Rodenticides, 360.-361sodi
Page 604 and 605: INDEX 601Safe Human Dose (SHD) appr
Page 606: INDEX 603drug metabolism factors, 7
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