PRINCIPLES OF TOXICOLOGY

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REFERENCES AND SUGGESTED READING 237 Cagen, S. Z., J. M. Jr., Waechter, S. S. Dimond, W. J. Breslin, J. H. Butala, F. W. Jekat, R. L. Joiner, R. N. Shiotsuka, G. E. Veenstra, and L. R. Harris, “ Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A.” Toxicological Sciences 50(1): 36–44 (1999). Carney, E. W., A. M. Hoberman, D. R. Farmer, R. W. Jr., Kapp, A. I. Nikiforov, M. Bernstein, M. E. Hurtt, W. J. Breslin, S. Z. Cagen, and G. P. Daston. “Estrogen modulation: tiered testing for human hazard evaluation.” American Industrial Health Council, Reproductive and Developmental Effects Subcommittee. Reproductive Toxicology 11(6): 879–892 (1997). Colborn, T., F. S. Vom Saal, and A. M. Soto, “Developmental effects of endocrine-disrupting chemicals in wildlife and humans.” Environmental Health Perspectives 101: 378–384 (1993). Crisp, T. M., E. M. Clegg, R. L. Cooper, W. P. Wood, D. G. Anderson, K. P. Baetcke, J. L. Hoffman, M. S. Morrow, D. J. Rodier, J. E. Schaeffer, L. W. Touart, M. G. Zeeman, and Y. M. Patel, “Environmental endocrine disruption: An effects assessment and analysis.” Environmental Health Perspectives 106 (Supplement 1): 11–56 (1998). Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), “Endocrine Disruptor Screening and Testing Advisory Commitee (EDSTAC) Final Report.” Washington, D.C. USEPA, editor, (1998). Faber, K. A., and C. L., Jr., Hughes, ”Clinical Aspects of Reproductive Toxicology” in Witorsch, R. J., ed., Reproductive Toxicology. 2nd edition. New York: Raven Press, Ltd, (1995). Gorospe, W. C., and M. Reinhard, “Toxic Effects on the Ovary of the Nonpregnant Female.” in Witorsch, R. J., ed., Reproductive Toxicology. 2nd edition. New York: Raven Press, Ltd, (1995). Koop, C. E., “The Latest Phoney Chemical Scare.” The Wall Street Journal, June 22, 1999. Manson, J. M., and L. D. Wise, “Teratogens.” in Amdur, M. O., Doull, J., and Klaassen C. D., eds., Casarett and Doull’s Toxicology: The Basic Science of Poisons. 4th edition. New York: Pergamon Press (1991). Matt, D. W., and J. F. Borzelleca, “Toxic Effects on the Female Reproductive System During Pregnancy, Parturition, and Lactation.” in Witorsch, R. J., ed., Reproductive Toxicology. 2nd edition. New York: Raven Press, Ltd, (1995). Mattison, D. R., D. R. Plowchalk, M. J. Meadows, A. Z. Al-Juburi, J. Gandy, and A. Malek, “Reproductive Toxicity: Male and Female Reproductive Systems as Targets for Chemical Injury.” Medical Clinics of North America 74: 391–411 (1990). McLachlan, J. A., Retraction: Synergistic activation of estrogen receptor with combinations of environmental chemicals, Science 277: 462–463 (1997). NagDas, S. K. “Effect of chlorpromazine on bovine sperm respiration.” Archives of Andrology 28: 195–200 (1992). Nair, R. S., F. W. Jekat, D. H. Waalkens-Berendsen, R. Eiben, R. A. Barter, and M. A. Martens, “Lack of Developmental/Reproductive Effects with Low Concentrations of Butyl Benzyl Phthalate in Drinking Water in Rats.” The Toxicologist, 48(1-S): 218 (1999). National Research Council, Committee on Hormonally Active Agents in the Environment, Board on Environmental Studies and Toxicology, Commission on Life Sciences, 1999. “ Hormonally Active Agents in the Environment.” National Academy Press, Washington. Nimrod, A. C. and W. H. Benson, “Environmental estrogenic effects of alkylphenol ethoxylates.” Critical Reviews in Toxicology 26: 335–364 (1996). Olsen, G. W., K. M. Bodner, J. M. Ramlow, C. E. Ross, and L. I. Lipshultz, “Have sperm counts been reduced 50 percent in 50 years? A statistical model revisited.” Fertility and Sterility 63: 887–893 (1995). Peltola, V., E. Mantyla, I. Huhtaniemi, and M. Ahotupa, “Lipid peroxidation and antioxidant enzyme activities in the rat testis after cigarette smoke inhalation or administration of polychlorinated biphenyls or polychlorinated naphthalenes.” Jo. of Androl. 15: 353–361 (1994). Safe, S. H., “Do environmental estrogens play a role in development of breast cancer in women and male reproductive problems?” Human and Ecological Risk Assessment 1: 17–23 (1995). Schardein, J. L. Chemically Induced Birth Defects. New York: Marcel Dekker, Inc (1985). Schilling, K., C. Gembardt, and J. Hellwig, “Reproduction toxicity of di-2-ethylhexyl phthalate (DEHP)” The Toxicologist, 48; (1-S): 692 (1985, 1999). Sharpe, R. M., J. S. Fisher, M. M. Millar, S. Jobling, and J. P. Sumpter, “Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production.” Environmental Health Perspectives 103(12): 1136–1143 (1995). Shepard, T. H., Catalog of Teratogenic Agents. 6th edition. Baltimore: Johns Hopkins University Press (1989).
238 REPRODUCTIVE <strong>TOXICOLOGY</strong> Sundaram, K., and R. J. Witorsch, “Toxic Effects on the Testes.” in Witorsch, R. J., ed., Reproductive Toxicology. 2nd edition. New York: Raven Press, Ltd, (1995). Thomas, J. A. “Toxic Responses of the Reproductive System.” In Amdur, M. O., Doull, J., and Klaassen, C. D., eds., Casarett and Doull’s Toxicology: The Basic Science of Poisons. 4th edition. New York: Pergamon Press (1991). vom Saal, F. S., B. G. Timms, M. M. Montano, P. Palanza, K. A. Thayer, S. C. Nagel, M. D. Dhar, V. K. Ganjam, S. Parmigiani, and W. V. Welshons, “ Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses.” Proceedings of the National Academy of Sciences 94(5): 2056–2061 (1997).
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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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Page 195 and 196: 184 PULMONOTOXICITY: TOXIC EFFECTS
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Page 199 and 200: 10 Immunotoxicity: Toxic Effects on
Page 201 and 202: 10.2 BIOLOGY OF THE IMMUNE RESPONSE
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Page 205 and 206: certain situations immunosuppressio
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Page 213 and 214: animal origin have also been shown
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Page 217 and 218: PART II Specific Areas of Concern P
Page 219 and 220: 210 REPRODUCTIVE TOXICOLOGY continu
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Page 225 and 226: 216 REPRODUCTIVE TOXICOLOGY gonadot
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Page 229 and 230: Figure 11.3 Cycle of follicular dev
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Page 235 and 236: 226 Figure 11.5 Developmental tree
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Page 249 and 250: 240 MUTAGENESIS AND GENETIC TOXICOL
Page 257 and 258: 248 Figure 12.5 Example of DNA addu
Page 267 and 268: TABLE 12-3 NTP and Gene-Tox Evaluat
Page 275 and 276: 266 CHEMICAL CARCINOGENESIS 13.1 TH
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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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300 CHEMICAL CARCINOGENESIS TABLE 1
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302 CHEMICAL CARCINOGENESIS with ex
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314 CHEMICAL CARCINOGENESIS Figure
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316 CHEMICAL CARCINOGENESIS similar
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322 CHEMICAL CARCINOGENESIS Figure
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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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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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