PRINCIPLES OF TOXICOLOGY

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Follicle-stimulating hormone (FSH), female reproductive toxicology, 22 I --223 Food chemicals, developmental toxicology and endocrine disruption, 232-235 Forensic toxicology, as research discipline, 6 Formaldehyde, toxicology, 385-388 Foxgloves, cardiac glycosides in, 419421 Frameshift mutation, genetic alteration and, 247-248 Free radicals, chemical mutagenesis and 239-240 Frequency-response graphs, 11, 15-16 Fulminant hepatic failure, hepatoxicity and, 124 Fumigants, 361.-362 ethylene oxide, 362 methyl bromide, 362 sulthydryl fluoride, 362 Fungicides, 358.-360 chlorothalonil, 359 copper compounds, 360 dithiocarbamates/thiocarbamates, 359 Fungi toxins, toxicology, 417419 Gap junctions, neurotransmitter activity, 147-149 Gases: lung absorption of, 45 pulmonotoxicity and exposure to, 178-179 Gas exchange mechanisms, pulmonotoxicity, 172-173 Gastrointestinal tract: metals ingestion, 329 arsenic, 336 cadmium exposure, 338-339 lead poisoning, 340.-341 mercury toxicology, 341-342 zinc toxicology, 342.-343 toxic agent absorption, 4143 determinant factors, 4243 organic acids and bases, 42 Gender characteristics: dose-response data, 23 xenobiotic metabolism, 8 1 Gene mutation tests, genetic toxicity assessment and, 247,249 Gene pool protection, occupationally-acquired mutagens and, 257 Genetically based developmental disorders: embryonic and fetal toxic responses and, 228 vs. developmental toxicology, 224-225 Genetic alteration mechanisms, genetic toxicology and, 245-25 1 Genetic damage biomarkers, occupational monitoring with, 260 Genetic disorders, table of, 250 Genetic makeup, dose-response data and, 25-26 Genotoxicity: antimony carcinogenicity risks, short-term studies with, 493 carcinogenesis and 270-272 metabolic activation, 277 risk assessment, 307-308 INDEX 585 chromosome structure and function, 244 epigenetic carcinogens, 273,278 genetic alteration mechanisms, 245-25 1 induction and consequences of genetic change: historical background, 239-240 occupational mutagens, spontaneous mutations, naturally occmring mutagens, 240-241 mammalian mutagenicity tests, 253-257 dominant lethal assays, 255 germ cell assays, 254 heritable translocation assay, 255 micronucleus testing, 255 primary DNA damage testing, 256 spermhead morphology assay, 255 transgenic mouse assays, 256 in vitro testing, 256-257 mitosis, meisosis and fertilization, 244-245 nonmammalian mutagenicity tests, 251-253 bacterial test systems, 252 Drosophila test systems, 253 plant assays, 253 transcription and translation fundamentals, 241-244 Germ cell assays, mutagenicity testing, 254 “Ginger jake” paralysis, organophosphate-induced delayed neuropathy (OPIDN), 349-350 Ginseng, saponins in, 419942 1 Glomerular filtration, glomerulus structure and, 13 1 Glomerular filtration rate (GFR): kidney loss and, 137 nephrotoxicity measurement, 1355136 Glomerulus, structure and function, 13 1 Glucose-6-phosphate dehydrogenase (G6PDH), red blood cell changes and 10 1 Glucuronidation: biotransformation reactions, 62, 72 microsomal enzymes, 62 Glutathione conjugation: aromatic amine exposure and, 101 biotransformation, 73-74 Glycols, toxicology, 384 Glycoproteins: hematopoiesis, 88-90 immunotoxicity, 192-193 Glycosides, in flowering plants, 419421 Glyphosate, structure and properties, 358 Gonadotropin releasing hormone (GnRH): female reproductive toxicology, 221-223 male reproductive toxicology, 2 16-2 17 Good laboratory practice (GLP) procedures, chronic animal bioassay, 290 G proteins, bacterial toxins, 416 Granulocyte-colony stimulating factor (GCS-F), hematopoiesis, 88-90 Granulocyte-macrophage colony stimulating factor (GM-CSF), hematopoiesis, 88.-90 Granulocytes, formation of, 93-94 Granulocytopenia, hematopoiesis, 90 Granulocytosis, hematopoiesis, 90
586 INDEX Hair, toxic agent excretion, 53 Haldane effect, carbon monoxide binding affinity, 97.-98 Halogenated alkanes, toxicology, 39 l-397 Halogenated hydrocarbons: dermal toxicity, acneiform dermatoses, 164 nephrotoxicity, 140 Halogenated methanes, toxicology, 3922397 Halotanes, spontaneous abortion and, 227 Halothane hepatitis, hepatocellular degeneration and death, 120 Haplens, immunotoxicity, 192 Hazard, defined 5 Hazard assessment, occupational health hazards control and, 531-536 anticipation of effects, 53 l--532 evaluation of effects, 533-536 recognilion of effects, 532-533 Hazard identification: ethical issues concerning, 507 risk assessment procedures, 438,442445 animal studies, 443445 cpidcmiologic studies and case reports, 443 toxicology research, 6 Hazard index approach, risk evaluation using, 466-468 arsenic risk assessment studies, 487-490 petroleum hydrocarbons exposure and risk studies, 484-486 Hazard quotient (H(2) calculations: risk assessment studies, 452454 arsenic risk assessment, 487490 petroleum hydrocarbons exposure and risk, 484486 risk evaluation using, 466468 Health care facilities, occupational hazard control case study of, 544-546 Health risk assessment: epidemiologic studies and, 515-516 VS. ecological risk assessment, 442 Health status, dose-response data and, 26 “Healthy worker effect,” bias in epidemiologic studies, 5 19-520 Heat-shock proteins, nephrotoxicity and 137 Hemangiosarcoma, hepatoxicity and, 123 Hematology, clinical terminology for, 90 Hematopoiesis, hematotoxicity and 88-90 Hematotoxicity: amine compounds, 399-402 anemias, 92 aromatic amine compounds, 400402 autoimmune hemolytic anemia, 10 1 basic concepts, 87-88 bone marrow suppression, 102-104 chemical leukemogenesis, 104 clinical terms and definitions, 90 hematopoiesis mechanisms, 88-90 inorganic nitrates/nitrites and chlorate salts, 999100 leukemias and lymphomas, 91 bone marrow suppression, 102-104 lymphoid series, 94-95 metals exposure: arsenic, 336 beryllium, 337~-338 lead poisoning, 340-341 methemoglobinemia, 100-101 myeloid series, 91-94 platelets (thrombocytes), 92-93 polymorphonuclear neutrophils (PMNs), 92.-93 red blood cells (RBC): erythrocytes, 91-92 oxygen transport: chemical impairment, 97-99 hemoglobin, 95.-96 red blood cells: antidotes for, 107 basophilic stippling, 108 cyanide poisoning, 105 hydrogen sulfide poisoning, 1055106 hypoxia, 96-97 oxygen transport: hemoglobin, 95-96 reptile and amphibian venoms, 423 425 solvent toxicology, benzene toxicity, 380 Hemoglobin: anemia and, 91.-92 hypoxia and, 97 nitrite/chlorate exposure and, 99-100 protein structure, 95-96 red blood cell (RBC) development, 9 1 Hemolytic anemia: autoimmune hemolytic anemia, 101 methemoglobin and, 100-101 Hemoproteins, biotransformation oxidations, 66 Hepatic encephalopathy, hepatoxicity and 125 Hepatic enzymes, hepatoxicity and measurement of, 126 Hepatocellular alteration, hepatoxicity and, 124 Hepatocellular carcinomas, hepatoxicity and, 123 Hepatocellular degeneration and death, 116-l 20 apoptosis, 117 calcium homeostasis, loss of, 120 endoplasmic reticulum damage, 116 immune reactions, 120 lipid peroxidation, 119 lysosomal damage, 117 macromolecular irreversible binding, 119-120 mitochondrial damage, 116 necrosis mechanisms, 117- 118 nuclei damage, 116-l 17 plasma membrane damage, 116 Hepatocytes, liver morphology, 115 Hepatotoxicity: cholestasis, 122 cirrhosis, 123 evaluation of, 124-127 blood tests, 125-127 morphologic evaluation, 125 toxicity symptoms, 124125
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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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TABLE 12-3 NTP and Gene-Tox Evaluat
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266 CHEMICAL CARCINOGENESIS 13.1 TH
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268 CHEMICAL CARCINOGENESIS TABLE 1
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270 CHEMICAL CARCINOGENESIS researc
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272 CHEMICAL CARCINOGENESIS Figure
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276
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280 CHEMICAL CARCINOGENESIS 13.4 MO
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286 CHEMICAL CARCINOGENESIS make a
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288 Figure 13.8 A genetic model of
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290 CHEMICAL CARCINOGENESIS Increas
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292 CHEMICAL CARCINOGENESIS may be
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294 CHEMICAL CARCINOGENESIS • The
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296 CHEMICAL CARCINOGENESIS evaluat
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298 CHEMICAL CARCINOGENESIS In rats
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302 CHEMICAL CARCINOGENESIS with ex
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316 CHEMICAL CARCINOGENESIS similar
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324 CHEMICAL CARCINOGENESIS Knudson
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326 PROPERTIES AND EFFECTS OF METAL
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332 TABLE 14.2 Target Organ Toxicit
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346 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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Page 559 and 560: GLOSSARY Glossary absorption The mo
Page 561 and 562: GLOSSARY 557 antipyretic An agent t
Page 563 and 564: GLOSSARY 559 chloracne An acne-like
Page 565 and 566: GLOSSARY 561 eczema A superficial i
Page 567 and 568: GLOSSARY 563 hemolytic anemia Anemi
Page 569 and 570: GLOSSARY 565 lipoprotein Any of a g
Page 571 and 572: GLOSSARY 567 necrosis Death of one
Page 573 and 574: pernicious anemia The progressive,
Page 575 and 576: GLOSSARY 571 cells have both endoth
Page 577 and 578: GLOSSARY 573 tolerance The ability
Page 579 and 580: 576 INDEX Allergic reaction (contin
Page 581 and 582: 578 INDEX Biotransformation (contin
Page 583 and 584: 580 INDEX Children’s health statu
Page 585 and 586: 582 INDEX Diet and nutrition (conti
Page 587: 584 INDEX Estrogens: endocrine disr
Page 591 and 592: 588 INDEX hnmunoglobulins: autoimmu
Page 593 and 594: 590 INDEX Loop of Henle, structure
Page 595 and 596: 592 INDEX Mixed exposure patterns,
Page 597 and 598: 594 INDEX Nutritional deficiencies,
Page 599 and 600: 596 INDEX Pesticides (continued) Pe
Page 601 and 602: 598 INDEX Relative potency factor (
Page 603 and 604: 600 INDEX Solvents (continued) phys
Page 605 and 606: 602 INDEX Tumorigenesis (continued)
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