PRINCIPLES OF TOXICOLOGY

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INDEX Absorbed dose, defined, 4 Absorption mechanisms: in human body, 35-36 metals pharmacokinetics, 328 organophosphateicarbamate pesticides, 347--348 solvent exposure, 3722373 toxic agents, 4145 gastrointestinal tract, 4143 lungs, 43345 skin, 43 Acceptable ambient-air level (AAAL), environmental exposure guidelines with, 3 1-32 Acetaldehyde, toxicology, 387-388 Acetone, toxicology, 3899390 Acetophone, toxicology, 389 Acetylation, biotransformation, 74 Acetylcholine (ACh): neurotransmitter activity, 148-149 reptile and amphibian venom toxicology, 424425 synaptic neurotoxicity, 15 1 Acetylcholinesterase (AChE): neurotransmitter activity, 148-149 organophosphateicarbamate pesticides, 347 organophosphate-induced delayed neuropathy (OPIDN), 350 synaptic neurotoxicity, 15 1 Acid anhydride, immunotoxicity, 203 Acneiform dermatoses, dermal toxicity, 163-164 Acquired immunity, immunotoxicity, 190 Acrolein, toxicology, 386, 388 Activation, xenobiotic metabolism, enzyme activity, 15 Active transport, toxic agents, 40 Acute accidental poisoning, toxicity data in studies of, 13 Acute exposure: defined 4 herbicides, 356 metals toxicity, 33 1 organochlorine insectides, 353 organophosphate/carbamate pesticides, 348-349 Acute myelogenous leukemia (AML), benzene exposure, 103-104 Acute renal failure (ARF), nephrotoxicity and, 137 Acute toxicity: defined, 4 errors in measurement of, 20 relative ranking system for, 19-20 Acute transforming retroviruses, oncogenes, 280 Adenomas: classification, 267-268 hepatoxicity and 123 Administration routes of carcinogens, carcinogenicity studies, 2955296 Administrative controls: carbon dioxide exposure studies, 549 control technologies for hazardous materials, 540 Adverse effects, dose-response data and, 27-28 Aerosols: metals as, 329 pulmonotoxicity and absorption of, 174-175 Aflatoxins, sources of, 419 Age characteristics: arsenic risk assessment studies, 489490 dose-response data, 23-24 xenobiotic metabolism, 82 Aggregation of disease, epidemiologic studies, 520 “Aging” pesticides, absorption and metabolism, 348 Agonists, natural venoms and toxin neurotoxicity, 411413 Air exposure measurements: antimony carcinogenicity risk studies, 495496 occupational health hazards control, sampling techniques, 534-536 Air pollutant gases, pulmonotoxicity, 180 Alcohol. See also Ethanol toxicology, 382-384 R-OH, 382-383 simple alcohols, 383-384 Aldehydes, toxicology, 385-388 Alicyclic solvents, toxicity, 378-379 Aliphatic organic solvents: toxicity, 377-378,402404 toxicology, 398402 Alkaloidal toxins: in flowering plants, 421 in mushrooms, 418419 Alkanes: halogenated alkanes, toxicology, 391-397 toxicity, 377-378 Alkylating agents: carcinogenicity, 274 genetic toxicity and 247,249 Alkylbenzenes, toxicology of, 380-381 Alkyl cyanides, toxicology, 404405 Allergens, allergic contact dermatitis, 162 Allergic reaction: contact dermatitis, 161-162 Principles 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 INDEX Allergic reaction (continued) defined 5 hymenoptera toxins, 427 immunotoxicity, 194 metals exposure, dermal contact, 330 pulmonotoxicity and respiratory response, 184 occupation-related disorders, 184 Allowable daily intake (ADI) measurement, risk assessment studies, 45 1454 Alveocapillary membrane complex, pulmonotoxicity, gas/vapor exposure, 1788179 Amatoxins, toxicology, 417-418 Amebic dysentery, natural toxins and, 416417 Ames assay: carcinogenicity, 273 mutagenicity testing with, 252 Amine compounds: relative base strength, 399 relative toxicity, 399 toxicology, 3988402 Aminita mushrooms, toxicology, 417418 Amino acid conjugation, biotransformation, 74 Amino acids, genetic toxicology and, 242-243 Aminoazo dyes, carcinogenicity, 274 y-Aminobutyric acid (GABA), neurotransmitter inhibition, 15 1 Aminopterin, developmental toxicology of, 230 Aminotransferase activities, hepatoxicity and measurement of, 127 Ammonia, aquatic toxicity interactions, 25 Amphibian venoms, toxicology, 423425 Analytical observational studies, characteristics of, 514 Anaphylaactic-type reaction, immunotoxicity and 194 Anaplasia, defined, 266 Androgens: developmental toxicology of, 230 male reproductive toxicology and, 2 17 Anemia: classification of, 92 hypoxia and, 97 lead poisoning and 108 red blood cell (RBC) development and, 91-92 Aneuploidy, chromosomal aberrations and, 250 Aniline, toxicology, 400402 Animal species/strain: carcinogenicity studies: human differences and, 2977299 reliability of extrapolation, 2999301 xenobiotic metabolism, enzyme variations, 79981 Animal studies: antimony carcinogenicity risks, rodent studies, 491494 carcinogenic activity, 2899299 human anatomic differences, 297-298 human cellular and biochemical differences, 298.-299 human physiologic differences, 298 relevant animal models, 297 data problems in, 14 extrapolation to human exposure, 28-33 carcinogenicity studies, reliability in, 299-301 environmental exposure guidelines, 31-32 exposure routes, 29-3 1 risk assessment studies, 443445 safe human dose (SHD) approach, 29 immunotoxicity assessment, 197-I 99 limits of, 21-22 Animal venoms and toxins: arthropod toxins and venoms, 426427 coelentrate (cnidarian) venoms, 428429 fish venoms and toxins, 425426 mollusc venoms and toxins, 427428 reptiles and amphibians, 423425 toxic marine invertebrates, 429430 Annelida, venom toxicology in, 430 Anoxia: neurotoxicity and, 150-I 5 1 red blood cell impairment and, 96697 Antagonism, dose-response data and, 24-26 Anthropogenic sources, metals exposure from, 334-335 Antibodies, immunotoxicity, 1922193 Anticholinesterase agents, synaptic neurotoxicity, 151 Anticipation of hazard effects, occupational health hazards control and, 53 l-532 Anticoagulants: clotting factor carboxylation and, 108 developmental toxicology of, 230 as rodenticides, 360 Anticonvulsive agents, developmental toxicology and 229 Antigen presenting cells (APC): allergic contact dermatitis, 161-162 immunotoxicity, 190-191 macrophages as, 93-94 Antigens, immunotoxicity, 190 Antimony, carcinogenic risk assessment, 490496 air and soil exposure equations, 495496 human studies, 491 putative mechanisms for, 4933494 rodent studies, 491493 short-term genetic toxicity studies, 493 weight of evidence characterization, 494496 Anti-neoplastic agents. See Chemotherapeutic agents Antivenin therapy: horse antivenins, 423 immunotherapy techniques, 43043 1 pharmacokinetics, 43 1 reptile and amphibian venoms, 425 Apamin, in bee venom, 427 Apoptosis: carcinogenesis and 285-289 hepatocellular degeneration and death, 117, 119 Applied dose, defined, 4 Applied toxicology, as research discipline, 6
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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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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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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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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: GLOSSARY 573 tolerance The ability
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
Page 593 and 594: 590 INDEX Loop of Henle, structure
Page 595 and 596: 592 INDEX Mixed exposure patterns,
Page 597 and 598: 594 INDEX Nutritional deficiencies,
Page 599 and 600: 596 INDEX Pesticides (continued) Pe
Page 601 and 602: 598 INDEX Relative potency factor (
Page 603 and 604: 600 INDEX Solvents (continued) phys
Page 605 and 606: 602 INDEX Tumorigenesis (continued)
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PRINCIPLES OF TOXICOLOGY

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