PRINCIPLES OF TOXICOLOGY

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TABLE 13.13 Continued 1-Nitropyrene 4-Nitropyrene N-Nitroso-n-butyl-N-(3-carboxypropyl)amine N-Nitroso-n-butyl-N-(4-hydroxybutyl)amine N-Nitrosodi-n-butylamine N-Nitrosodiethanolamine N-Nitrosodi-n-propylamine N-Nitroso-N-ethylurea (N-ethyl-N-nitrosourea (ENU) 4-(N-Nitrosomethylamino)-1-(3-pyridyl)- 1-butanone N-Nitroso-N-methylurea N-Nitrosomethylvinylamine N-Nitrosomorpholine N-Nitrosonornicotine N-Nitrosopiperidine N-Nitrosopyrrolidine N-Nitrososarcosine Norethisterone Ochratoxin A 4,4-Oxydianiline Oxymetholone Phenacetin Phenazopyridine hydrochloride Phenoxybenzamine hydrochloride Phenytoin Polybrominated biphenyls (PBBs) Polychlorinated biphenyls (PCBs) Polycyclic aromatic hydrocarbons (PAHs) Procarbazine hydrochloride Progesterone a Color Index. was a “cancer epidemic” in this nation attributable to environmental exposure to pollutants shown to cause cancer in animals has been found to be inaccurate. In the absence of large percentages of cancers attributable to environmental contaminants or occupational exposures, then, we are faced with determining how much of our cancer risk is inevitable (due to aging processes or perhaps genetic predisposition) or could be offset by changes to lifestyle factors such as smoking and diet. Genetic Makeup of Individuals 13.9 CANCER AND OUR ENVIRONMENT 307 1,3-Propane sultone β-propiolactone Propylene oxide Propylthiouracil Quartz [under “silica, crystalline (respirable size)”] Reserpine Saccharin Safrole Selenium sulfide Silica, crystalline (respirable size) Streptozotocin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Tetrachloroethylene (perchloroethylene) Tetranitromethane Thioacetamide Thiourea Toluene diisocyanate o-Toluidine o-Toluidine hydrochloride Toxaphene 2,4,6-Trichlorophenol 1,2,3-Trichloropropane Tridymite Tris(2,3-dibromopropyl) phosphate Urethane (Urethan; ethyl carbamate) 4-Vinyl-1-cyclohexene diepoxide The understanding of the role that genetics plays in carcinogenesis increased greatly in the 1990s and the relationship between genetic makeup and carcinogenesis is rapidly becoming a dominant area of cancer research. To date there have been more than 600 genetic traits associated with an increased risk of neoplasia. This relatively recent area of research is focused on how changes in the phenotypic expression of certain enzymes may alter the activation, detoxification, or repair mechanisms and thereby enhance the genetic damage produced by a particular chemical exposure. Genetic predisposition now accounts for perhaps 5–10 percent of all cancers, and it has been identified as a component
308 CHEMICAL CARCINOGENESIS TABLE 13.14 IARC Carcinogens Exposure circumstances Aluminum production Auramine, manufacture of Boot and shoe manufacture and repair Coal gasification Coke production Furniture/cabinetmaking Hematite mining with exposure to radon Iron and steel founding Isopropanol manufacture (strong-acid process) Magenta, manufacture of Painter Rubber industry Strong-inorganic-acid mists containing sulfuric acid Agents and groups of agents Aflatoxins, naturally occurring 4-Aminobiphenyl Arsenic and arsenic compounds Asbestos Azathioprine Benzene Benzidine Beryllium and beryllium compounds N,N-Bis(2-chloroethyl)-2-naphthylamine (Chlomaphazine) Bis(chloromethyl) ether and chloromethyl methyl ether 1,4-Butanediol dimethanesulfonate (Busulphan; Myleran) Cadmium and cadmium compounds Chlorambucil 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1nitrosourea (methyl-CCNU; Semustine) Chromium VI compounds Ciclosporin Cyclophosphamide Diethylstilboestrol (DES) Epstein–Barr virus Erionite Ethylene oxide Estrogen therapy, postmenopausal Estrogens, nonsteroidal Estrogens, steriodal Group 1: Carcinogenic to Humans (75) Helicobacter pylori (infection with) Hepatitis B virus (chronic infection with) Hepatitis C virus (chronic infection with) Human immunodeficiency virus type 1 (infection with) Human papillomavirus type 16 Human papillomavirus type 18 Human T-cell lymphotropic virus type I Melphalan 8-Methoxypsoralen (methoxsalen) MOPP and other combined chemotherapy, including alkylating agents Mustard gas (sulfur mustard) 2-Naphthylamine Nickel compounds Opisthorchis viverrini (infection with) Oral contraceptives, combined Oral contraceptives, sequential Radon and its decay products Schistosoma haematobium (infection with) Silica, crystalline Solar radiation Talc containing asbestiform fibers Tamoxifen 2,3,7,8-Tetrachlorodibenzo-para-dioxin Thiotepa Treosulfan Vinyl chloride Mixtures Alcoholic beverages Analgesic mixtures containing phenacetin Betel quid with tobacco Coal tar pitches Coal tars Mineral oils, untreated and mildly treated Salted fish (Chinese style) Shale oils Soots Tobacco products, smokeless Tobacco smoke Wood dust (continued)
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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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Page 265 and 266: 256 MUTAGENESIS AND GENETIC TOXICOL
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358 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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22.2 EXPOSURE LIMITS 525 The TLVs
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modified “reference doses” to r
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observation process, followed by re
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• Hazard-specific training to ens
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22.3 PROGRAM MANAGEMENT 533 Conside
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Figure 22.1 22.3 PROGRAM MANAGEMENT
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fundamental viability of the work p
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Figure 22.2. 22.3 PROGRAM MANAGEMEN
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• Physical assessment and fit tes
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The study was designed to minimize
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TABLE 22.3 Margins of Safety at For
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top, and numerous slots with smalle
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TABLE 22.5 Comparison of Time-Weigh
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• Housing or building code violat
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• Environmental exposure limits,
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GLOSSARY Glossary absorption The mo
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GLOSSARY 557 antipyretic An agent t
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GLOSSARY 559 chloracne An acne-like
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GLOSSARY 561 eczema A superficial i
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GLOSSARY 563 hemolytic anemia Anemi
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GLOSSARY 565 lipoprotein Any of a g
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GLOSSARY 567 necrosis Death of one
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pernicious anemia The progressive,
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GLOSSARY 571 cells have both endoth
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GLOSSARY 573 tolerance The ability
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576 INDEX Allergic reaction (contin
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578 INDEX Biotransformation (contin
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580 INDEX Children’s health statu
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582 INDEX Diet and nutrition (conti
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584 INDEX Estrogens: endocrine disr
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586 INDEX Hair, toxic agent excreti
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588 INDEX hnmunoglobulins: autoimmu
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590 INDEX Loop of Henle, structure
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592 INDEX Mixed exposure patterns,
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594 INDEX Nutritional deficiencies,
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596 INDEX Pesticides (continued) Pe
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598 INDEX Relative potency factor (
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600 INDEX Solvents (continued) phys
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602 INDEX Tumorigenesis (continued)
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PRINCIPLES OF TOXICOLOGY

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