PRINCIPLES OF TOXICOLOGY - Biology East Borneo

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200 IMMUNOTOXICITY: TOXIC EFFECTS ON THE IMMUNE SYSTEMTABLE 10.4 Examples of Agents that Produce Dermal Contact SensitivityDrugsMetalsBenzocaine BerylliumThimerosal CadmiumNeomycin ChromatesResins GoldAcrylic resins MercuryEpoxy resins NickelFormaldehyde resins SilverPhenolic resins ZirconiumOther industrial chemicalsEthylenediamineParaphenylenediamine and other dyesAntioxidantsChlorinated hydrocarbonsDinitrochlorobenzeneMe rcaptansIgE-mediated. Table 10.5 lists examples of common agents associated with respiratory allergy.Occupational asthma represents a special kind of inhalation disorder that is distinct from typicalrespiratory allergy. In general, a longer sensitization period is required, and symptoms may resemblean early-phase reaction, a late-phase reaction, or both. IgE may be responsible for some, but not all,of the manifestations of occupational asthma. In fact, the role of the immune system in occupationalasthma may be different for asthma initiated or provoked by high-molecular-weight compounds,low-molecular-weight compounds, and irritatants.The potential for immunosuppression from occupational and environmental exposure tochemicals has been suggested by numerous in vitro studies and experiments in laboratory animals.Direct evidence for clinical immunosuppression following workplace or environmental exposuresis extremely limited. However, there are many well-documented examples of the development orexacerbation of autoimmunity from chemical exposure. Most of these examples (shown in Table10.6) are drugs, and for agents such as procainamide, up to 80 percent of patients treatedchronically will develop increased levels of autoimmune antibodies. Many of these drugs producesigns and symptoms resembling systemic lupus erythematosus, while others produce autoimmunedisease of the kidney, liver, thyroid, and other organs; scleroderma; or autoimmune hemolyticanemia. Evidence suggests that several environmental contaminants may also have the ability toeither produce or worsen autoimmune disease, although the association with autoimmune diseaseis often less well substantiated.TABLE 10.5 Examples of Agents that Product Respiratory AllergyMoldsDusts and Small ParticulatesAspergillus Coffe eCladosporum EnzymesHormodendrum FlourPenicillium MitesRhizopus SawdustPollens (various) Pet danderCockroach proteins
10.6 SPECIFIC CHEMICALS THAT ADVERSELY AFFECT THE IMMUNE SYSTEM 201TABLE 10.6 Examples of Agents Associatedwith Autoimmune DiseaseDrugsAcebutalolAllopurinolAlprenololAmiodaroneAmpicillinBleomycinCaptoprilCarbamazepineCephalosporinChlorpromazineChlorthalidoneDapsoneDiphenylhydantoinEthosuximideFenoprofenIodineIsoniazidLithiumLovastatinMefenamic acidMethyldopaMinocyclineNitrofurantoinPenicillaminePhenylbutazonePropylthiouracilQuinidineSulfonamidesAmino acidsL-TryptophanL-CanavanineEnvironmental/industrial chemicalsAromatic aminesCadmiumChlordaneChorpyrifosChromiumFormaldehydeGoldHydrazineMe rcuryParaquatPentachlorophenolPerchlorethyleneSilicon (silica)ThalliumTrichloroethyleneVinyl chloride
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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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Page 168 and 169: 8 Dermal and Ocular Toxicology: Tox
Page 170 and 171: 8.2 FUNCTIONS 159corneum is the pri
Page 172 and 173: 8.3 CONTACT DERMATITIS 161TABLE 8.2
Page 174 and 175: 8.3 CONTACT DERMATITIS 163mucous me
Page 176 and 177: 8.3 CONTACT DERMATITIS 165light to
Page 178 and 179: 8.4 SUMMARY 167The structure of the
Page 180 and 181: 9 Pulmonotoxicity: Toxic Effects in
Page 182 and 183: 9.1 LUNG ANATOMY AND PHYSIOLOGY 171
Page 192 and 193: 9.2 MECHANISMS OF INDUSTRIALLY RELA
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Page 196 and 197: 9.3 SUMMARY 185Industrially Related
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Page 200 and 201: 190 IMMUNOTOXICITY: TOXIC EFFECTS O
Page 218 and 219: 11 Reproductive ToxicologyREPRODUCT
Page 220 and 221: 11.1 MALE REPRODUCTIVE TOXICOLOGY 2
Page 228 and 229: 11.2 FEMALE REPRODUCTIVE TOXICOLOGY
Page 234 and 235: 11.3 DEVELOPMENTAL TOXICOLOGY 225de
Page 236 and 237: 11.3 DEVELOPMENTAL TOXICOLOGY 227af
Page 238 and 239: 11.3 DEVELOPMENTAL TOXICOLOGY 229ri
Page 240 and 241: 11.3 DEVELOPMENTAL TOXICOLOGY 231to
Page 242 and 243: 11.4 CURRENT RESEARCH CONCERNS 233T
Page 244 and 245: 11.4 CURRENT RESEARCH CONCERNS 235
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Page 248 and 249: 12 Mutagenesis and Genetic Toxicolo
Page 250 and 251: 12.2 GENETIC FUNDAMENTALS AND EVALU
Page 252 and 253: 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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