PRINCIPLES OF TOXICOLOGY

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Area under the tissue concentration-time curve (AUC), risk assessment studies, exposure pathways and dosages, 448449 Aromatic amines: carcinogenicity, 275 hemolytic anemia and 100-101 toxicology, 400402 Aromatic hydrocarbon solvents, toxicity, 379-382 polycyclic aromatic hydrocarbon (PAH) carbons, 381-382 substituted aromatic compounds, 380-381 Aromatic nitro compounds, toxicity, 402404, 403-404 Arrhythmias, cardiotoxicity and 419424 Arsenic: carcinogenicity of, 333-334 risk assessment studies of, 4866490 toxicology of, 336.-337 Arteriosclerosis, platelet formation and 93 Arthropod toxins and venoms, toxicology, 426427 Asbestosis, industrial-related exposure, 182 Asclepius, digitalis compounds in, 419 Asthma: immunotoxic agents, 200 industrial or occupational-related incidence, 185 urticaria and 163 Atropine, organophosphateicarbamate pesticides exposure treatment, 35 1 Attribution, evaluations for, occupational health practices for, 5055506 Autoimmune disease: hemolytic anemia, oxidative stress and 101 immunotoxic agents, 201 Autoimmunity, immunotoxicity, 195 Average daily intake (ADI): arsenic risk assessment studies, 487490 petroleum hydrocarbons exposure and risk studies, 485486 Safe Human Dose (SHD) calculations, 29 Bacillus thuringiensis, chemical structure, 355 Bacterial test systems, nonmammalian mutagenicity tests, 252 Bacterial toxins, toxicology of, 415416 Bagassosis, 184 Base analogues, genetic toxicity and, 247 Basepair changes, genetic toxicity and 247 Basophilic stippling, lead poisoning and 108 Basophils, formation of, 93-94 Batrachatoxin, toxicology 425 Bee venom, toxicology 427 Behavioral tests, neurotoxicity assessment, 153 organophosphate/carbamate pesticides, 350 Benchmark dose (BMD), risk assessment studies, 452454 Benign tumors: defined 266 vs. malignant tumors, 267-268 Benzene exposure: INDEX 577 bone marrow suppression, 1022104 chemical leukemogenesis, 104 solvent carcinogenicity, 376 solvent toxicology, 377,3799382 Benzene hexachloride compounds (BHCs), organochlorine insectides, mechanisms of, 352 Benzidine, toxicology, 401402 Benzo(a)pyrene (BaP): genetic alteration and 247 toxicology, 381-382 Beryllium: carcinogenicity of, 333-334 dermal exposure to, 330 toxicology of, 337-338 Beryllosis, immunotoxicity, 202 Bias, in epidemiologic studies, 5 19-520 Bile flow, cholestasis, 122 Bilirubin conjugation, hepatoxicity and 126 Bioactivation: detoxification and 83-85 solvent exposure, 373 Bioavailability measurements, arsenic risk assessment studies, 487490 Biological exposure indices (BEI), organophosphate/carbamate pesticides, 351-352 Biological insecticides, 353-355 Bacillus thuringiensis, 355 pyrethrum and pyrethrins, 354 rotenone, 355 synthetic pyrethroids, 354-355 Biological monitoring: arsenic risk assessment studies, 489490 organochlorine insectides, 353 organophosphateicarbamate pesticides, 350-35 1 risk assessment studies, exposure pathways and dosages, 449 Biomarkers: of metal exposure, 335-336 risk assessment studies, exposure pathways and dosages, 449 Biotransformation: bioactivation-detoxification balance, 83-85 defined 57 liver’s role in, 113 metals speciation, 328 reactions: acetylation, 74-77 amino acid conjugation, 74-77 glucouronidation, 72 hydrolyses, 70-7 1 methylation, 74-77 oxidation, 65.-70 reductions, 72 sulfation, 72, 74 xenobiotic-metabolizing enzyme inhibition, 77-83 sites of, 62-64
578 INDEX Biotransformation (continued) solvent exposure, 373 toxic agent elimination, 5 1 Bipyridyl compounds, structure and characteristics, 356-358 Black widow spiders, venom toxicology in, 427 Bladder, structure and function, nephrotoxicity, 134 Blast forming unit-erythrocyte (BFU-E), red blood cell development, 91-92 Blood cells, formation and differentiation, 88-90 Blood flow, kidneys, 129-130 Blood pressure regulation, nephrotoxicity and 134 Blood tests, hepatoxicity and 1255127 Blood urea nitrogen (BUN), nephrotoxicity measurement, 136 B-lymphocytes: formation of, 94495 immunotoxicity, 190.--191 clinical assessment, 196 Bone marrow production, hematopoiesis, 88-90 Bone marrow suppression: causative chemical agents, 102 mechanisms of, 1022104 Botulinurn poisoning, toxicology, 415-416 BPDE, genetic alteration and, 2477248 Brain development, lead poisoning studies and, 2355236 Brain lesions, neurotoxicants and 150 Breakage-first hypothesis, chromosomal aberrations, 250-25 1 Brevetoxins, toxicology, 417 Bridging necrosis, hepatocellular degeneration and death, 117 British Anti-Lewisite (BAL), metals metabolism and storage, 330 Bromomethane, nephrotoxicity 140 Brown recluse spider, venom toxicology of, 426 Bufotenin, in amphibians, 425 Bufotoxins: in amphibian venoms, 425 cardiac glycosides in, 419 o-Bungarotoxin, reptile and amphibian venom toxicology, 424 425 B-Bungarotoxin, reptile and amphibian venom toxicology, 424425 Byssinosis, pulmonotoxicity and 184 Cadmium: carcinogenicity of, 333-334 female reproductive toxicology, 221 male reproductive toxicology, 2 12-2 13 nephrotoxicity, 13 8 occupational health surveillance program for exposure to, 505 toxicology of, 338-339 Caffeine, neurotoxicity, 152 Calcium, hepatocellular degeneration and death, homeostasis, loss of, 120 Calcum channels, natural venoms and toxin neurotoxicity, 4 13 Caloric restrictions, carcinogenicity studies, 296-297 Cancer: incidence and mortality in US., 319-321 risk assessment studies: nonthreshold modeling, 455459 pesticides, household exposure risk table, 470 volatile organic compounds (VOCs), indoor air exposure risk table, 469 somatic cell mutation theory of, 240 terminology of, 266 Cancer slope factor: lead carcinogenicity, 341 risk assessment studies, arsenic risk assessment, 4899490 solvent toxicology, 301 Carbamate insecticides, 346-352 absorption and metabolism, 3477348 acute effects, 348-349 biological monitoring, 350-351 chronic effects, 349 delayed neurotoxicity, 3499350 historical background 346-347 intoxication treatment, 35 1 mechanism of action, 347 neurobehavioral sequelae, 350 regulatory information, 35 l-352 Carbon black, antimony carcinogenicity risks compared with, 492 Carbon dioxide, occupational hazard control case study of, 547-549 Carbon disulfide: spontaneous abortion and, 227 toxicology, 406407 Carbon monoxide, oxygen transport impairment and 97-99 Carbon tetrachloride: nephrotoxicity, 140 toxicology, 377, 396-397 Carboxyhemoglobin, carbon monoxide binding affinity, 97-98 Carboxylic acids, toxicology, 3899390 Carcinogenicity studies. See Chemical leukogenesis; Mutagenesis alcohol as risk factor, 3 15 antimony, 490-496 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 cancer risk assessment studies, regulatory issues, 456459 chemical carcinogenesis: administration routes and vehicles, 295-296 anatomic differences, human-animal comparisons, 297-298
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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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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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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: 576 INDEX Allergic reaction (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
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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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