PRINCIPLES OF TOXICOLOGY

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TABLE 3.4 Important Cytochrome P450s a 68 Forms Present in Substrates/ Subfamily Rat Rabbit Human Mouse Tissue Reactions Inducers Inhibitors 3A 1,2 6 3,4,5,7 11,13 erythromycin N deM, glucocorticoids DEX, cimetidine, TAO MI complex, PCN, macrolides, TAO naringenin cyclosporine, quinidine, clotrimazole, testosterone, and cortisol phenobarbital 6β-OH, mephenytoin (rat), benzphetamine, nifedipine, and other dihydropyridines 4A 1,2,3,8 4,5,6,7 9,11 10,12 liver, kidney Lauric acid and peroxisome proliferators, prostaglandin ω-OH DEHP, clofibrate pregnancy (4A4) 4B 1 1 1 lung valproic acid a Abbreviations: deE = deethylation deM = demethylation DEHP = di(2-ethylhex yl)phthalate DEX = dex amethasone EH = ex trahepatic GI = gastrointestinal tract Kid = kidney MI = metabolic-intermediate 3MC = 3-methylcholanthrene NBI = N-benzylimidazole OH = hydrox ylation PAH = polycyclic aromatic hydrocarbons PCB = polychlorinated biphenyls PCN = pregeneolone 16α carbonitrile PB = phenobarbital RIF = rifampicin TAO = troleandomycin TCDD = 2,3,7,8-tetrachlorodibenzo-p-diox in
Figure 3.8 Cytochrome P450–catalyzed oxidations. 3.2 BIOTRANSFORMATION REACTIONS 69
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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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Page 31 and 32: 16 GENERAL PRINCIPLES OF TOXICOLOGY
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Page 73 and 74: BIOTRANSFORMATION: A BALANCE BETWEE
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Page 77 and 78: Figure 3.5 Diagrammatic rendition o
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Page 87 and 88: TABLE 3.6 Changes in Rat Hepatic Dr
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Page 91 and 92: TABLE 3.7 Induction of Xenobiotic-M
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Page 103 and 104: Figure 4.1 Formation of blood. Matu
Page 105 and 106: TABLE 4.2 Leukemias and Lymphomas 4
Page 107 and 108: 4.3 THE MYELOID SERIES 93 to contra
Page 109 and 110: function and response to stimuli, (
Page 111 and 112: Hypoxia can result from a variety o
Page 113 and 114: 4.7 INORGANIC NITRATES/NITRITES AND
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Page 117 and 118: 4.10 BONE MARROW SUPPRESSION AND LE
Page 119 and 120: 4.12 TOXICITIES THAT INDIRECTLY INV
Page 121 and 122: 4.15 ANTIDOTES FOR HYDROGEN SULFIDE
Page 123 and 124: REFERENCES AND SUGGESTED READING 10
Page 125 and 126: 112 HEPATOTOXICITY: TOXIC EFFECTS O
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120 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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