PRINCIPLES OF TOXICOLOGY

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500 OCCUPATIONAL AND ENVIRONMENTAL HEALTH Illnesses associated with hazardous exposures both in the workplace and in the general environment have been recognized for thousands of years. For example, the toxic effects of lead, including abdominal pain, pallor (anemia), and paralysis, appear to have been described by several observers among the ancient Greeks and Romans. In the first known textbook of occupational medicine, De Morbis Artificum Diatriba, the Italian physician Bernardino Ramizzini (1633–1717), often called the father of occupational medicine, described diseases of the occupations and instructed physicians of the time: “and to the questions recommended by Hippocrates, the physician should add one more— what is your occupation?” In the United States, Dr. Alice Hamilton (1869–1970) had a major role in establishing occupational medicine as a legitimate clinical discipline. Dr. Hamilton, the first woman appointed to the faculty of the Harvard Medical School, wrote in her autobiography: “American medical authorities had never taken industrial diseases seriously . . . employers could, if they wished, shut their eyes to the dangers their workmen faced, for nobody held them responsible, while the workers accepted the risks with fatalistic submissiveness.” Among her many legacies, Dr. Hamilton fought, without success, the introduction of tetraethyl lead into gasoline, correctly predicting that it would result in widespread lead contamination of the environment and adverse health effects in the exposed population. How big a problem is occupational diseases? Two kinds of numbers are informative: counts and rates. Suppose there are two industries, one employing 1,000 workers nationally, the other employing 50,000 workers nationally. Suppose that the incidence of work-related asthma is 12 per 100 workers per year in the first industry, and only 4 per 100 workers per year in the second industry. By this measure, the first industry is more hazardous. But 120 workers in the first industry develop asthma each year, compared to 2,000 workers in the second industry. From a public health point of view, the larger burden of illness in the second industry might merit more attention. Counts and rates both provide useful information, but they can yield different conclusions. There are two principal sources of data that help answer this question: employer reports, and insurance records. Employers are required by OSHA to record all work-related injuries and illnesses, and each year, a sample of employers provide information to the Bureau of Labor Statistics. This serves as the national data source on occupational illnesses. As for insurance, the Workers Compensation system acts as the health insurer for workers with occupational illnesses, and the records of claims made or claims paid also serves as a potential data source. In both cases, there is considerable under-reporting. Employers and workers may not recognize that an illness is work-related, or employers may deny a worker’s claim of work-relatedness. Employers may in some cases fail to report recognized cases. Sometimes, occupational illnesses arise long after the exposure, perhaps after employment has ended, making data recording difficult. Other sources of information on occupational illnesses exist. Examples include clinical laboratories, which can yield data on cases of elevated blood lead, and physician reporting of specific diseases. While such sources are important in specific settings, none has gained widespread use. TABLE 20.1 Leading Categories of Work-Related Diseases Occupational lung diseases: asbestosis, byssinosis, silicosis, coal worker’s pneumoconiosis, lung cancer, occupational asthma Musculoskeletal injuries: disorders of the back, trunk, upper extremity, neck, lower extremity, trauma-induced Raynaud’s phenomenon Occupational cancers (other than lung cancer): leukemia, mesothelioma, cancers of the bladder, nose, and liver Occupational cardiovascular diseases: hypertension, coronary artery disease, acute myocardial infraction Disorders of reproduction: infertility, spontaneous abortion, teratogenesis Neurotoxic disorders: peripheral neuropathy, toxic encephalitis, psychoses, extreme personality change (exposure-related) Noise-induced hearing loss Dermatologic conditions: dermatoses, burns (scaldings), chemical burns, contusions (abrasions) Psychological disorders: neuroses, personality disorders, alcoholism, drug dependency
20.1 DEFINITION AND SCOPE <strong>OF</strong> THE PROBLEM 501 TABLE 20.2. Number of Reported Occupational Illnesses by Category of Illness, Private Industry, 1998 (in thousands) Dust Disorders Disorders Associated Diseases Toxic Due to with Total Skin of the Respiratory Physical Repeated All Industry Cases Diseases Lungs Conditions Poisoning Agents Trauma Other All private industry 391.9 53.1 2.1 17.5 4.0 16.6 253.3 45.4 Agriculture, forestry and fishing 4.3 2.4
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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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Page 505: 20 Occupational and Environmental H
Page 509 and 510: 20.4 HUMAN RESOURCES IMPORTANT TO O
Page 511 and 512: treatment, or medical removal from
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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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