PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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13.9 CANCER AND OUR ENVIRONMENT 305TABLE 13.13 Agents Listed in the Report on Carcinogens (8th Edition) from the National ToxicologyProgram, as Known or Suspected Human CarcinogensKnown Human CarcinogensAminobiphenyl (4-aminodiphenyl)ErioniteAnalgesic mixtures containing phenacetinLead chromateArsenic compounds, inorganicMelphalanAsbestosMethoxsalen [with ultraviolet A (UVA) therapy]AzathioprineMineral oilsBenzeneMustard gasBenzidine2-Naphthylamine (β-naphthylamine)Bis(chloromethyl) etherPiperazine Estrone Sulfate1,4-Butanediol dimethylsulfonate (Myleran)RadonChlorambucilSodium equilin sulfate1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosoureaSodium estrone sulfateSootsChloromethyl methyl etherStrontium chromateChromium hexavalentTarsCoal tarThiotepa [tris(1-aziridinyl)phosphine sulfide]Coke oven emissionsThorium dioxideCreosote (coal)Tris(1-aziridinyl)phosphine sulfide (thiotepa)Creosote (wood)Vinyl chlorideCyclophosphamideZinc chromateCyclosporin A (cyclosporine A; ciclosporin)DiethylstilbestrolAgents Reasonably Anticipated to be Human CarcinogensAcetaldehyde2-AcetylaminofluoreneAcrylamideAcrylonitrileAdriamycin (doxorubicin hydrochloride)2-Aminoanthraquinoneo-Aminoazotoluene1-Amino-2-methylanthraquinoneAmitroleo-Anisidine hydrochlorideAzacitidine (5-azacytidine)Benz[a]anthraceneBenzo[b]fluorantheneBenzo[j]fluorantheneBenzo[k]fluorantheneBenzo[a]pyreneBenzotrichlorideBeryllium aluminum alloyBeryllium chlorideBeryllium fluorideBeryllium hydroxideBeryllium oxideBeryllium phosphateBeryllium sulfate tetrahydrateBeryllium zinc silicateBeryl oreBis(chloroethyl) nitrosourea (BCNU)Bis(dimethylamino)benzophenoneBromodichloromethane1,3-ButadieneButylated hydroxyanisole (BHA)CadmiumCadmium chlorideCadmium oxideCadmium sulfateCadmium sulfideCarbon tetrachlorideCeramic fibersChlorendic acidChlorinated paraffins (C12, 60% chlorine)1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea(CCNU)Chloroform3-Chloro-2-methylpropene4-Chloro-o-phenylenediaminep-Chloro-o-toluidinep-Chloro-o-toluidine hydrochlorideChlorozotocin(continued)
306 CHEMICAL CARCINOGENESISTABLE 13.13 ContinuedCI a Basic Red 9 monohydrochlorideCisplatinp-CresidineCristobalite [under “Silica, crystalline(respirable size)” ]CupferronDacarbazine2,4-Diaminoanisole sulfate2,4-DiaminotolueneDibenz[a,h]acridineDibenz[a,j]acridineDibenz[a,h]anthracene7H-Dibenzo[c,g]carbazoleDibenzo[a,e]pyreneDibenzo[a,h]pyreneDibenzo[a,i]pyreneDibenzo[a,l]pyrene1,2-Dibromo-3-chloropropane1,2-Dibromoethane [ethylene dibromide (EDB)]1,4-Dichlorobenzene (p-dichlorobenzene)3,3-Dichlorobenzidine3,3-Dichlorobenzidine dihydrochlorideDichlorodiphenyltrichloroethane (DDT)1,2-Dichloroethane (ethylene dichloride)1,3-Dichloropropene (technical-grade)DiepoxybutaneN,N-Diethyldithiocarbamic acid 2-chloroallylesterDEHP; bis(2-ethylhexyl phthalate)]DiethylnitrosamineDiethyl sulfateDiglycidyl resorcinol ether1,8-Dihydroxyanthraquinone [Danthron]3,3-Dimethoxybenzidine4-Dimethylaminoazobenzene3,3-DimethylbenzidineDimethylcarbamoyl chloride1,1-Dimethylhydrazine (UDMH)DimethylnitrosamineDimethyl sulfateDimethylvinyl chloride1,6-Dinitropyrene1,8-Dinitropyrene1,4-DioxaneDirect Black 38Direct Blue 6Disperse Blue 1EpichlorohydrinEstradiol-17bEstroneEthinylestradiolEthyl acrylateEthylene oxideEthylene thioureaEthyl methanesulfonateFormaldehyde (gas)FuranGlasswoolGlycidol hexachlorobenzeneα-Hexachlorocyclohexaneβ-Hexachlorocyclohexaneγ-HexachlorocyclohexaneHexachlorocyclohexaneHexachloroethaneHexamethylphosphoramideHydrazineHydrazine sulfateHydrazobenzeneIndeno[1,2,3-cd]pyreneIron dextran complexKepone (chlordecone)Lead acetateLead phosphateLindaneMestranol2-Methylaziridine (propylenimine)5-Methylchrysene4,4-Methylenebis(2-chloraniline)4,4-Methylenebis(N,N-dimethylbenzenamine)Methylene chloride4,4-Methylenedianiline4,4-Methylenedianiline dihydrochlorideMethylmethanesulfonateN-Methyl-N-nitro-N-nitrosoguanidineMetronidazoleMirexNickelNickel acetateNickel carbonateNickel carbonylNickel hydroxideNickel hydroxideNickeloceneNickel oxideNickel subsulfideNitrilotriacetic acido-Nitroanisole6-NitrochryseneNitrofenNitrogen mustard hydrochloride2-Nitropropane(continued)
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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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Page 266 and 267: 12.5 OCCUPATIONAL SIGNIFICANCE OF M
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Page 274 and 275: 13 Chemical CarcinogenesisCHEMICAL
Page 276 and 277: 13.1 THE TERMINOLOGY OF CANCER 267H
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Page 298 and 299: 13.5 TESTING CHEMICALS FOR CARCINOG
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Page 330 and 331: 13.11 SUMMARY 321from non-Hodgkin
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Page 334 and 335: 14 Properties and Effects of Metals
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Page 356 and 357: 15.1 ORGANOPHOSPHATE AND CARBAMATE
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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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