PRINCIPLES OF TOXICOLOGY

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15 Properties and Effects of Pesticides EFFECTS PROPERTIES OF PESTICIDES AND EFFECTS OF PESTICIDES JANICE K. BRITT The term “pesticide” encompasses a group of chemical compounds that are used for the elimination or control of pests. Pesticides are grouped into classes based on their target of action and include such groups as insecticides, fungicides, herbicides, rodenticides, and molluscicides. Pesticides have economic and public health benefits and have been used over the years for the control of vectorborne diseases such as malaria and Rocky Mountain Spotted Fever, for the promotion of agricultural production in the United States as well as in other countries, and by homeowners for the control of domestic pests (e.g., household and garden pests). Individuals may be exposed to pesticides either occupationally (e.g., from working in a pesticide formulating plant or from commercial pesticide application) or environmentally (e.g., from food products such as fruits and vegetables treated for pests). Individuals may also be exposed to pesticides at their residences (e.g., from use as home or garden insecticide). The most commonly used pesticides have recently been reported by the U.S. Environmental Protection Agency (USEPA) (see Table 15.1). The registration and regulatory requirements concerning pesticides are governed under the Federal Insecticide, Fungicide, and Rodenticide Act, also known as FIFRA. Rules aimed at the protection of TABLE 15.1 Most Commonly Used Pesticides in the United States Most Commonly Used Pesticides in U.S. Agricultural Crop Production Atrazine Metolachlor Metam sodium Methyl bromide Dichloropropene Most Commonly Used Pesticides in Nonagricultural Sectors of the United States Home and garden market 2,4-Dichlorophenoxyacetic acid Glyphosate Dica mba MCPP Diazinon Industrial/commercial/government uses 2,4-Dichlorophenoxyacetic acid Chlorpyrifos Glyphosate Methyl bromide Copper sulfate Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams, Robert C. James, and Stephen M. Roberts. ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc. 345
346 PROPERTIES AND EFFECTS OF PESTICIDES agricultural and greenhouse workers who used pesticides were passed in 1992 by the USEPA and are located in 40 Code of Federal Regulations Parts 156 and 170. The Occupational Safety and Health Administration (OSHA) as well as the American Conference of Governmental Industrial Hygienists (ACGIH) also publishes guidelines for occupational exposures to pesticides in air. This chapter will discuss the classes of the most commonly used pesticides and will include a discussion of the following with respect to these pesticide classes: • Uses • Mechanism of action • Pharmacokinetics • Acute and chronic effects from exposure • Biological monitoring • Treatment of pesticide overexposure • Regulatory information 15.1 ORGANOPHOSPHATE AND CARBAMATE INSECTICIDES Introduction, Use, and History of Organophosphates and Carbamates Organophosphate compounds have become widely used pesticides as replacements for the more persistent organochlorine insecticides (discussed in Section 15.2). Organophosphate insecticides do not bioaccumulate in tissues and organisms or accumulate in the environment as do the organochlorines. In fact, chlorpyrifos, an organophosphate compound, has become a widely used termiticide, serving as a substitute for the more persistent organochlorine compounds used in the past. However, because of the acute toxicity of some of the organophosphate compounds, another class of pesticide— pyrethrins (discussed in Section 15.3)—are becoming more widely used. Examples of commonly used organophosphates include Dursban (chlorpyrifos), Knox Out 2FM (diazinon), and Vapona (dichlorvos) (see Figure 15.1 for examples of organophosphate insecticides). Examples of carbamate pesticide products commonly used are Sevin (carbaryl) and Temik (aldicarb) (see Figure 15.2 for examples of carbamate insecticides). It should be noted that organophosphate compounds are used not only as pesticides; chemicals in this class are also used as therapeutic agents for the treatment of glaucoma and myasthenia gravis in humans. For example, the organophosphate echothiophate iodide is used to treat glaucoma. The first organophosphate insecticide developed was tetraethyl pyrophosphate (TEPP), developed in Germany during World War II as a substitute for nicotine. Because TEPP, although an effective compound, was unstable in the environment, there was an effort to develop more stable compounds. This effort resulted in the development of the organophosphate insecticide parathion in 1944. (CH 3) 2CH N CH 3 N S O P OC 2H 5 CH 3O CH 3O OC2H5 Diazinon Malathion Figure 15.1 Examples of organophosphate insecticides. S P S CHCOOC 2H 5 CH 2COOC 2H 5
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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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274 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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396 PROPERTIES AND EFFECTS OF ORGAN
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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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