PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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TABLE 3.4 Important Cytochrome P450s aSubfamilyForms Present inRat Rabbit Human MouseTissue3A 1,2 6 3,4,5,7 11,13 erythromycin N deM,TAO MI complex,cyclosporine, quinidine,testosterone, and cortisol6β-OH, mephenytoin(rat), benzphetamine,nifedipine, and otherdihydropyridines4A 1,2,3,8 4,5,6,7 9,11 10,12 liver, kidney Lauric acid andprostaglandin ω-OH4B 1 1 1 lung valproic acidSubstrates/Reactions Inducers Inhibitorsglucocorticoids DEX,PCN, macrolides, TAOclotrimazole,phenobarbitalperoxisome proliferators,DEHP, clofibratepregnancy (4A4)cimetidine,naringenina Abbreviations: deE = deethylationdeM = demethylationDEHP = di(2-ethylhex yl)phthalateDEX = dex amethasoneEH = ex trahepaticGI = gastrointestinal tractKid = kidneyMI = metabolic-intermediate3MC = 3-methylcholanthreneNBI = N-benzylimidazoleOH = hydrox ylationPAH = polycyclic aromatic hydrocarbonsPCB = polychlorinated biphenylsPCN = pregeneolone 16α carbonitrilePB = phenobarbitalRIF = rifampicinTAO = troleandomycinTCDD = 2,3,7,8-tetrachlorodibenzo-p-diox in68
Figure 3.8 Cytochrome P450–catalyzed oxidations.3.2 BIOTRANSFORMATION REACTIONS 69
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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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Page 68 and 69: 2.5 SUMMARY 53the transfer from liv
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Page 72 and 73: 58 BIOTRANSFORMATION: A BALANCE BET
Page 74 and 75: 60Figure 3.3 Xenobiotic metabolism
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Page 130 and 131: 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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REFERENCES AND SUGGESTED READING 12
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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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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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