PRINCIPLES OF TOXICOLOGY

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Rodenticides, 360.-361 sodium fluoroacetate, 361 thallium sulfate, 360-361 Rosary bean seeds, peptide and protein toxins in, 421422 Rotenone, chemical structure, 355 Route specificity, metals carcinogenicity and 333-334 Rubella virus, developmental toxicology and 224 Safe Human Dose (SHD) approach: calculation of, 29 risk assessment studies, 450454 dose metrics, 459460 Safety, defined 5 Safety and health professions, toxic agent distribution studies, 35-37 foreign compound absorption and disposition, 35536 target tissue significance, 36-37 Safety factors. See Uncertainty factors Salmonella species: Ames assay, carcinogenicity, 273 bacterial test systems, 252 Sampling techniques: carbon dioxide exposure studies, 5477549 evaluation of hazardous effects, 534-536 lead-based paint case study, 550-552 Saponins, in flowering plants, 4 19-42 1 Sarcomas, hepatoxicity and 123 Satellite, chromosome structure and function, 244 Saturated aliphatic solvents, toxicity, 3777378 Scorpion venom, toxicology, 426 Sea anemones, venom toxicology, 428429 Second messenger system, natural venoms and toxins and 414415 Secretory systems, tubular secretion and 133 Sertoli cells, cell-type specific toxicity, 214-215, 218 Serum albumin levels, hepatoxicity and 125 Serum bilirubin levels, hepatoxicity and 125 Serum enzymes, hepatoxicity and measurement of, 126 Serum sickness syndrome, 194 antivenin therapy and 43 1 Service delivery, for occupational medicine, 5066507 Shellfish toxins, toxicology, 417 Short-term cancer bioassays: antimony carcinogenicity risks, 493 carcinogenic potential assessment, 29 l-292 Short-term exposure limit (STEL), solvent exposure, 368,372 Sickle cell anemia, mutation mechanisms in, 25 1 Signal transduction pathways: natural venoms and toxins, 414-415 oncogenes, 281-283 Silicosis, industrial-related exposure, 182 Simple liver acinus, liver morphology, 114 Sinus cavities, pulmonotoxicity, 170 INDEX 599 Sister chromatid exchange (SCE), occupational monitoring with, 260 Skin: defensive role of, 159 functions, 158-160 histology, 1577158 toxic agent absorption, 43 toxic agent excretion, 53 Skin cancer, dermal toxicity, 164 Smoking: cadmium toxicology and 338-339 cancer incidence and 3 13-3 15 carboxyhemoglobin and, 98 developmental loxicology and 230 female reproductive toxicology, 221-222 lung cancer incidence, 180-l 8 1 platelet formation and, 93 pulmonotoxicity, 180-l 8 1 Sodium channel inactivation, natural venoms and toxin neurotoxicity, 413414 Sodium fluoroacetate, toxicity, 361 Sodium ions, action potential mechanisms, 1466147 Soil screening levels (SSLs): antimony carcinogenicity risk studies, 495496 arsenic risk assessment studies, 487490 risk assessment using, 480 Solenopsins, fire ant venom, 427 Solvents: absorption, distribution and excretion mechanisms, 372-373 acute toxic effects, 376-377 aldehydes toxicity, 385-388 alicyclic solvent toxicity, 378.-379 aromatic hydrocarbon solvent toxicity, 379-382 polycyclic aromatic hydrocarbon (PAH) carbons, 381-382 substituted aromatic compounds, 380.-381 carboxylic acid toxicity, 389-390 carcinogenicity, 375-376 central nervous system depression, 374 ester toxicity, 390 ether toxicity, 390-391 exposure potential, 367-368 glycols, 384 halogenated alkane toxicity, 391-397 methane compounds, 392-397 immunotoxicity, 203 ketone toxicity, 388G389 male reproductive toxicology, 2 13 Sertoli cell specificity, 2 15 membrane/tissue irritation, 374-375 neuronal membrane disruption by, 149 nitrile (alkyl cyanide) toxicity, 404405 nitro compound toxicity, 402404 nitrogen-substituted solvent toxicity, 398.-402 aromatic amino acid compounds, 400402 occupational exposure limits (OELs), 368, 371 peripheral nervous system effects, 374 phenol toxicity, 3844385
600 INDEX Solvents (continued) physicochemical properties, 368-370 pyridine series toxicity, 405 R-OH alcoholic compound toxicity, 3822383 saturated alphatic solvent toxicity, alkanes, 377-378 simple alcohol compound toxicity, 383-384 spontaneous abortion and 227 structural principles, 368 sulfur-substituted solvent toxicity, 4055407 unsaturated alphatic solvent toxicity, olefins, 378 Somatic mutation theory: chemical carcinogenesis, 269 mutagenesis and, 240 Source isolation procedures, control technologies for hazardous materials, 538 Speciation of metals: biological factors, 328 nonbiological factors, 327 Specific immunity, immunotoxicity, 189 Spermatogenesis, toxic susceptibility, 210-212 Sperm cells: cell-type specific toxicity and development of, 2133214 endocrine disruption research and sperm cell counts, 2333235 Spermhead morphology assay, mutagenicity testing, 255 Spider venom, toxicology of, 427 Sponges, venom toxicology in, 430 Spontaneous abortion, developmental toxicology, 225227 Spontaneous mutations, genetic toxicology and 240-241 Standardized mortality ratio (SMR), epidemiologic studies, 5 1775 18 Standardized rate ratio (SRR), epidemiologic studies, 517 Staphylococcal alpha toxin, toxicology, 416 Statistical analysis, occupational health hazards control; air sampling procedures, 534.-536 Steatosis, hepatotoxicity and 120-121 Steroid hormones, male reproductive toxicology and 217 Sting rays, venom toxicology, 425 Stonefish, venom toxicology, 425 Storage mechanisms in body, metals exposure and 330 Study evaluation, risk assessment studies, animal vs. human information, 444-445 Styrene, toxicology of, 380-38 1 Subacute exposure, defined, 4 Subcellular fractionation, xenobiotic metabolism, 64 Subchronic exposure, defined, 4 Sublinear cumulative dose-response curve, 17-18 Substitution of chemicals, control technologies for hazardous materials, 537-538 “Sufficiently similar” chemicals, risk evaluation using, 4655468 Sulfatases, sulfation biotransformation, 72-73 Sulfation, biotransformation reactions, 72-73 Sulfhemoglobin, hydrogen sulfide poisoning and 106 Sulfotransferases, sulfation biotransformation, 72-73 Sulfur-substituted solvents, toxicology, 405407 Sulfiuyl fluoride, toxicity, 362 Supralinear cumulative dose-response curve, 17-l 8 Surrogate chemical risk technique, petroleum hydrocarbons exposure and risk studies, 4833486 Surveillance activities, occupational health practice and, 504-505 Sweat, toxic agent excretion, 53 Synapse, neurotoxic agents, 15 1 Synergism: dose-response data and 24426 endocrine disruption research and estrogen synergy, 234-235 Synthetic pyrethroids, chemical structure, 354 Systemic toxicity, defined, 4 Talcum powder, antimony carcinogenicity risks compared with, 492 Target organ dose: carcinogenic@ studies, reliability of extrapolation in animal studies, 2999301 defined, 4 metals toxicity, 332 petroleum hydrocarbons exposure and risk studies, 4855486 Target tissue, toxic agent absorption and distribution, 36-37 Tautomeric shifts, genetic toxicity and 247 Teratogens: embryonic and fetal toxic responses and 228 fetal alcohol sydrome, 230 Tetanus poisoning, toxicology, 415416 Tetracyclines, developmental toxicology of, 230 Tetraethyl pyrophosphate (TEPP), history of use, 346 Tetrodotoxin: in fish venoms, 425 mollusc venom and toxin toxicology, 428 toxicology, 4 16 Thalidomide: developmental toxicology and, 224 tissue organization disruption, 228-229 female reproductive toxicology, 223 Thallium sulfate, toxicity, 360-361 Therapeutic agents, nephrotoxicity of, 141-142 Therapeutic dosages, medications, table of, 470 Thiazoles, toxicology, 406407 Thiocarbamates, structure and toxicity, 359 Thiocyanate, cyanide poisoning and formation of, 105 Threshold distribution models, cancer risk assessment studies, 456459 Threshold dose: cumulative dose-response curve, 16-17 risk asscssmcnt studies, 4499454
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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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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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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 and 588: 584 INDEX Estrogens: endocrine disr
Page 589 and 590: 586 INDEX Hair, toxic agent excreti
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: 598 INDEX Relative potency factor (
Page 605 and 606: 602 INDEX Tumorigenesis (continued)
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