PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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TABLE 16.1 Physicochemical Properties of Representative Solvents and Related MaterialsChemical CAS No. Molecular FormulaMolecularWeight(g/mol)MeltingPoint (°F)Boiling Point(°F)Vapor Pressure(mm Hg)Water Solubility(mg/L) Vapor Density Specific GravityHalogenatedCarbon tetrachloride 56-23-5 CCl4 153.8 –9 170 91 793 5.32 1.59Chloroform 67-66-3 CHCl3 119.4 –82 143 160 7,920 4.12 1.48Methyl bromide 74-83-9 CH3Br 95.0 –137 38 1,444 900 3.36 1.73Methyl chloride 74-87-3 CH3Cl 50.5 –144 –12 3,800 15,200 2.15 ND aMethylene chloride 75-09-2 CH2Cl2 62.5 –139 104 350 13,000 ND 1.33Trichloroethene 79-01-6 C2HCl3 131.4 –99 189 58 1,100 4.53 1.5Vinyl chloride 75-01-4 CH2CHCl 84.9 –256 7 3.3 2,760 1.78 0.91NonhalogenatedAcetaldehyde 75-07-0 CH3CHO 44.1 –190 69 740 Miscible 1.52 0.79Acetone 67-64-1 (CH3)2CO 58.1 –140 133 180 Miscible ND 0.79Acrolein 107-02-8 C2H3CHO 56.1 –126 127 210 208,000 1.94 0.84Aniline 62-53-3 C6H5NH2 93.1 21 363 0.6 34,000 3.22 1.02Benzene 71-43-2 C6H6 78.1 42 176 75 1,750 2.7 0.88Benzidine 92-87-5 NH2(C6H4)2NH2 184.3 239 752 low 400 6.36 1.25Benzo(a)pyrene 50-32-8 C20H12 252 179 >360 >1 0.00162 8.7 1.35Carbon disulfide 75-15-0 CS2 76.1 –169 116 297 1,190 2.67 1.26Dimethylaniline 121-69-7 C6H5N(CH3)2 121.2 36 378 1 1,450 4.17 0.961,4-Dioxane 123-91-1 C4H8O2 88.2 50 213 30 Miscible 3.03 1.03Ethanol 64-17-5 C2H5OH 46.1 –173 173 44 Miscible 1.59 0.79Ethyl acetate 141-78-6 C4H8O2 88.1 –118 171 100 64,000 3 0.89Ethyl ether 60-29-7 (C2H5)2O 74.1 –177 94 440 69,000 2.55 0.71Ethylene glycol 107-21-1 C2H4(OH)2 62.1 9 388 0.06 1,000 2.14 1.11Formaldehyde 50-00-0 HCHO 30.0 –134 –6
TABLE 16.1 (Continued)Chemical CAS No. Molecular FormulaMolecularWeight(g/mol)MeltingPoint (°F)Boiling Point(°F)Vapor Pressure(mm Hg)Water Solubility(mg/L) Vapor Density Specific GravityMethanol 67-56-1 CH3OH 32.1 –144 147 96 Miscible ND 0.79Methyl ethyl ketone 78-93-3 CH3OC2H5 72.1 –86.3 79.6 77.5 353,000 (10°C) 2.41 0.81Naphthalene 91-20-3 C10H8 128.2 176 424 0.08 31 4.42 1.15Nitrobenzene 98-95-3 C6H5NO2 123.1 42 411 0.3 (77°F) 2,090 4.3 1.2Nitromethane 75-52-5 CH3NO2 61.0 –20 214 28 110,000 2.11 1.14Phenol 108-95-2 C6H5OH 94.1 109 359 0.4 82,800 3.24 1.06Pyridine 110-86-1 C5H5N 79.1 –44 240 16 Miscible 2.72 0.98Styrene 100-42-5 C6H5(C2H4) 104.2 –23 293 5 310 3.6 0.91Tetrahydrofuran 109-99-9 C4H8O 72.1 –163 150 131 Miscible 2.5 0.89Toluene 108-88-3 C6H5CH3 92.1 –139 232 21 526 3.2 0.87a No data.370
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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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Page 334 and 335: 14 Properties and Effects of Metals
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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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