PRINCIPLES OF TOXICOLOGY

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7.3 Agents that Act on the Synapse 151 7.4 Interactions of Industrial Chemical with Other Substances 151 7.5 General Population Exposure to Environmental Neurotoxicants 152 7.6 Evaluation of Injury to the Nervous System 152 7.7 Summary 154 References and Suggested Reading 155 8 Dermal and Ocular Toxicology: Toxic Effects of the Skin and Eyes 157 William R. Salminen and Stephen M. Roberts 8.1 Skin Histology 157 8.2 Functions 158 8.3 Contact Dermatitis 160 8.4 Summary 167 References and Suggested Reading 168 CONTENTS ix 9 Pulmonotoxicity: Toxic Effects in the Lung 169 Cham E. Dallas 9.1 Lung Anatomy and Physiology 169 9.2 Mechanisms of Industrially Related Pulmonary Diseases 181 9.3 Summary 185 References and Suggested Reading 186 10 Immunotoxicity: Toxic Effects on the Immune System 189 Stephen M. Roberts and Louis Adams 10.1 Overview of Immunotoxicity 189 10.2 Biology of the Immune Response 189 10.3 Types of Immune Reactions and Disorders 194 10.4 Clinical Tests for Detecting Immunotoxicity 195 10.5 Tests for Detecting Immunotoxicity in Animal Models 197 10.6 Specific Chemicals that Adversely Affect the Immune System 199 10.7 Multiple-Chemical Sensitivity 203 10.8 Summary 205 References and Suggested Reading 205 PART II SPECIFIC AREAS <strong>OF</strong> CONCERN 207 11 Reproductive Toxicology 209 Robert P. DeMott and Christopher J. Borgert 11.1 Male Reproductive Toxicology 210 11.2 Female Reproductive Toxicology 218 11.3 Developmental Toxicology 224 11.4 Current Research Concerns 232 11.5 Summary 236 References and Suggested Reading 236
x CONTENTS 12 Mutagenesis and Genetic Toxicology 239 Christopher M. Teaf and Paul J. Middendorf 12.1 Induction and Potential Consequences of Genetic Change 239 12.2 Genetic Fundamentals and Evaluation of Genetic Change 241 12.3 Nonmammalian Mutagenicity Tests 251 12.4 Mammalian Mutagenicity Tests 253 12.5 Occupational Significance of Mutagens 257 12.6 Summary 261 References and Suggested Reading 263 13 Chemical Carcinogenesis 265 Robert C. James and Christopher J. Saranko 13.1 The Terminology of Cancer 266 13.3 Carcinogenesis by Chemicals 268 13.4 Molecular Aspects of Carcinogenesis 280 13.5 Testing Chemicals for Carcinogenic Activity 289 13.6 Interpretation Issues Raised by Conditions of the Test Procedure 292 13.7 Empirical Measures of Reliability of the Extrapolation 299 13.8 Occupational Carcinogens 301 13.9 Cancer and Our Environment: Factors that Modulate Our Risks to Occupational Hazards 304 13.10 Cancer Trends and Their Impact on Evaluation of Cancer Causation 319 13.11 Summary 321 References and Suggested Reading 323 14 Properties and Effects of Metals 325 Steven G. Donkin, Danny L. Ohlson, and Christopher M. Teaf 14.1 Classification of Metals 325 14.2 Speciation of Metals 327 14.3 Pharmacokinetics of Metals 328 14.4 Toxicity of Metals 331 14.5 Sources of Metal Exposure 334 14.6 Toxicology of Selected Metals 336 14.7 Summary 343 References and Suggested Reading 343 15 Properties and Effects of Pesticides 345 Janice K. Britt 15.1 Organophosphate and Carbamate Insecticides 346 15.2 Organochlorine Insecticides 352 15.3 Insecticides of Biological Origin 353
Page 1 and 2: PRINCIPLES OF TOXICOLOGY
Page 3 and 4: This book is printed on acid-free p
Page 5 and 6: vi CONTRI BUTORS PAUL J. MIDDENDORF
Page 7: viii CONTENTS 4 Hematotoxicity: Che
Page 11 and 12: xii CONTENTS III APPLICATIONS 435 1
Page 13 and 14: PREFACE Purpose of This Book Princi
Page 15 and 16: ACKNOWLEDGMENTS A text of this unde
Page 17 and 18: PART I Conceptual Aspects Principle
Page 19 and 20: 4 GENERAL PRINCIPLES OF TOXICOLOGY
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44 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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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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