Toxicology of Insecticides

1 Introduction.- 1.1. Toxicolog.- 1.2. General Patterns of Pesticide Us.- 1.3. Economic and Legal Aspects of Pesticide Us.- 1.4. Reference.- 2 General Principles of Insecticide Toxicology.- 2.1. Evaluation of Toxicity.- 2.1.1. Toxicity Tests Against Insects and Other Invertebrates.- 2.1.1a. Graphical Method for Estimating LD50.- 2.1.1b. Goodness-of Fit (x2 Test) and Confidence Limit.- 2.1.1c. Symptomatological Observation.- 2.1.2. Toxicological Evaluation in Higher Animals.- 2.1.2a. Selection of Test Animals.- 2.1.2b. Acute Toxicity Data.- 2.1.2c. Chronic Toxicity and Other Nonacute Toxicity Tests.- 2.1.2d. Observation of Toxic Symptoms.- 2.2. Analytical Methods for Insecticides.- 2.2.1. Chromatographic Analysis of Insecticide Residues.- 2.2.1a. Sampling, Extraction, and Cleanup.- 2.2.1b. Separation and Detection of Residues.- 2.2.2. Other Confirmatory Techniques for Residue Analysis.- 2.2.2a. Chemical Reactions.- 2.2.2b. Spectroscopic Methods.- 2.2.2c. Biological and Biochemical Assay.- 2.3. References.- 3 Classification of Insecticides.- 3.1. History and General Groupings of Insecticidal Compounds.- 3.2. Chlorinated Hydrocarbon Insecticides.- 3.2.1.DDT Analogue.- 3.2.2. Benzene Hexachloride.- 3.2.3. Cyclodiene Compound.- 3.3. Organophosphorus Insecticide.- 3.3.1. Pyrophosphates and Related Compounds.- 3.3.2. Phosphorohalides and Cyanides.- 3.3.3. Dialkylarylphosphates, Phosphorothioates, and Phosphorodithioates.- 3.3.4. Trialkylphosphates and Thiophosphates.- 3.4. Carbamate Insecticides.- 3.4.1. Naphthylcarbamates.- 3.4.2. Phenylcarbamates.- 3.4.3. Heterocyclic Dimethylcarbamates.- 3.4.4. Heterocyclic Methylcarbamates.- 3.4.5. Oximes.- 3.5. Thiocyanate Insecticides.- 3.6. Dinitrophenols.- 3.7. Fluoroacetate Derivatives.- 3.8. Acaricidal Chemicals: Sulfonates, Sulfones, Sulfides, and Nitrogen-Containing Compounds.- 3.9. Fumigants.- 3.10. Inorganic Insecticides.- 3.10.1. Arsenicals.- 3.10.2. Inorganic Fluorides.- 3.11. Botanical Insecticides.- 3.11.1. Nicotinoids.- 3.11.2. Rotenoids.- 3.11.3. Pyrethroids.- 3.11.3a. Pyrethrum.- 3.11.3b. Synthetic Pyrethroids.- 3.12. Synergists.- 3.13. References.- 4 Modes of Action of Insecticides.- 4.1. Introduction.- 4.2. Classification of Insecticides by Their Actions.- 4.3. The Nervous System.- 4.3.1. Mammalian Nervous System.- 4.3.1a. The Somatic System.- 4.3.1b. The Autonomic Nervous System.- 4.3.1c. The Electric (Axonic) Conduction of Nerve Impulses.- 4.3.1d. The Chemical Transmission of Nerve Impulses.- 4.3.2. Insect Nervous System.- 4.4. Chlorinated Hydrocarbon Insecticides.- 4.4.1. DDT and Its Analogues.- 4.4.1a. Symptomatology and Characteristics.- 4.4.1b. Action of DDT on Nerves and Theories of Its Mode of Action.- 4.4.1c. Theories of Structure-Toxicity Relationships.- 4.4.2. ?-BHC (Lindane).- 4.4.2a. Symptomatology.- 4.4.2b. Theories of Structure-Toxicity Relationships.- 4.4.3. Cyclodiene Insecticides.- 4.4.3a. Symptomatology.- 4.4.3b. Theories of Structure-Toxicity Relationships.- 4.5. Naturally Occurring Botanical Insecticides.- 4.5.1. Pyrethroids and Synergists.- 4.5.2. Nicotinoids.- 4.5.3. Rotenoids.- 4.6. Organofluorine Compounds: Fluoroacetate and Its Analogues.- 4.7. Anticholinesterases: Organophosphorus and Carbamate Insec ticides.- 4.7.1. Organophosphorus Compounds.- 4.7.1a. Symptoms.- 4.7.1b. Inhibition.- 4.7.1c. Recovery.- 4.7.1d. Aging.- 4.7.2. Carbamates.- 4.7.2a. Action.- 4.7.2b. Symptoms.- 4.8. Inhibitors of Respiratory Enzymes.- 4.8.1. Inhibitors of the Electron Transport System.- 4.8.2. Inhibitors of Oxidative Phosphorylation.- 4.9. Inhibitors of Mixed-Function Oxidases.- 4.10. Chlordimeform and Its Analogues.- 4.11. References.- 5 Metabolism of Insecticides by Animals and Plants.- 5.1. General Types of Metabolic Activities.- 5.2. Primary Metabolic Processes.- 5.2.1. Oxidation Through Mixed-Function Oxidase Systems.- 5.2.2. Reduction.- 5.2.3. Hydrolytic Processes: Metabolism of Esters and Ethers.- 5.2.4. Glutathione-Mediated Metabolism.- 5.2.4a. Glutathione-Catalyzed Metabolism.- 5.2.4b. Glutathione S-Transferases.- 5.3. Conjugation Systems: Secondary Metabolic Processes.- 5.3.1. Glucuronide or Glucuronic Acid Conjugation.- 5.3.2. Sulfate Conjugation or Ethereal Sulfate Synthesis.- 5.3.3. Glycine Conjugation or Hippuric Acid Synthesis.- 5.3.4. Cysteine Conjugation or Mercapturic Acid Synthesis.- 5.3.5. Histidine, Lysine, and Glutamine Conjugation.- 5.3.6. Glucoside Formation.- 5.3.7. Cyanide-Thiocyanate Detoxification.- 5.3.8. Methylation.- 5.3.9. Acetylation and Coupling with CoA.- 5.3.10. Glutathione Conjugations.- 5.3.11. Other Examples and Possibilities of Conjugations.- 5.4. Metabolic Reactions Characteristic of Each Group of Insecti- cidal Chemicals.- 5.4.1. Chlorinated Hydrocarbon Insecticides.- 5.4. la. Dehydrochlorination.- 5.4.1b. Reductive and Hydrolytic Dechlorination.- 5.4.1c. Oxidative Reactions.- 5.4.1d. Metabolism of Aliphatic Chlorinated Hydrocarbons: Fumigants and Metabolic Fragments.- 5.4.1e. Metabolism of Halogenated Aromatic Compounds.- 5.4.1f. DDT Metabolism.- 5.4. lg. Methoxychlor Metabolism.- 5.4.1h. BHC Metabolism.- 5.4. li. Aldrin and Dieldrin Metabolism.- 5.4. lj. Isodrin and Endrin Metabolism.- 5.4.1k. Metabolism of Heptachlor and Chlordane Analogues.- 5.4.1l. Endosulfan Metabolism.- 5.4.2. Metabolic Reactions Specific to Organophosphates.- 5.4.2a. General Reactions.- 5.4.2b. Enzyme Systems Involved in the Degradation of Organophosphates.- 5.4.2c. Schradan and Dimefox Metabolism.- 5.4.2d. Trichlorfon, Dichlorvos, and Naled Metabolism.- 5.4.2e. Bidrin, Azodrin, Phosphamidon, Mevinphos, and Ciodrin Metabolism.- 5.4.2f. Metabolism of Parathion and Analogues.- 5.4.2g. Diazinon, Chlorfevinphos, and Coumaphos Metabolism.- 5.4.2h. Demeton, Phorate, and Disulfoton: Oxidation of Thioether Side-Groups.- 5.4.2i. Metabolism of Malathion, Acethion, and Dimethoate: Degradation Through Hydrolytic Cleavage of Side-Chains.- 5.4.3. Metabolism of Carbamate Insecticides.- 5.4.3a. General Patterns.- 5.4.3b. Oxidative Metabolism of Carbamates.- 5.4.3c. Carbaryl Metabolism.- 5.4.3d. Substituted Phenylcarbamate.- 5.4.3e. Oxime Insecticide: Aldicarb Metabolism.- 5.4.4. Metabolism of Botanical and Other Insecticides.- 5.4.4a. Nicotine Metabolism.- 5.4.4b. Rotenone Metabolism.- 5.4.4c. Pyrethrin I, Allethrin, Dimethrin, and Phthalthrin Metabolism.- 5.5. References.- 6 Entry of Insecticides into Animal Systems.- 6.1. Penetration of Insecticides Through the Insect Cuticle.- 6.1.1. Morphology of the Insect Cuticle.- 6.1.2. Insect Cuticles as Membranes.- 6.1.3. Factors Influencing the Rate of Penetration: Chemical Nature of Insecticides.- 6.1.4. Factors Influencing Penetration of Insecticides : Effects of Cuticular Components.- 6.1.5. Effect of Carriers and Solvents.- 6.1.5a. Oil.- 6.1.5b. Detergents.- 6.1.5c. Dusts.- 6.2. Routes of Insecticide Entry into Insects.- 6.3. Routes of Insecticide Entry into Higher Animals.- 6.3.1. Penetration of Insecticides Through Mammalian Skin.- 6.3.2. Other Routes of Entry into Higher Animals.- 6.4. References.- 7 Dynamics of Insecticide Movement in the Animal Body.- 7.1. Total Intake-Elimination Dynamics.- 7.2. Transport of Insecticides by Blood and Body Fluid.- 7.3. Distribution and Redistribution Within the Animal Body.- 7.3.1. Distribution After Acute Administration.- 7.3.2. Distribution After Chronic Dosing and Dynamics of Redistribution.- 7.4. Factors Affecting Storage and Release.- 7.5. Penetration and Distribution into Vital Organs and Tissues.- 7.5.1. Nervous System.- 7.5.2. Transfer to Fetus and Reproductive Organs.- 7.6. Elimination of Insecticides: Excretion and Secretion.- 7.6.1. Biliary and Urinary Excretion.- 7.6.2. Secretion in Milk.- 7.7. References.- 8 Movement of Insecticides in the Environment.- 8.1. Introduction.- 8.2. Residues of Insecticides.- 8.2.1. General.- 8.2.2. Terrestrial Plants Including Agricultural Crops.- 8.2.3. Soils.- 8.3. Movement of Residues in the Environment.- 8.3.1. Water- and Air-Mediated Transport.- 8.3.2. Long-Range Transport.- 8.3.3. Mathematical Models for Insecticide Movement.- 8.4. References.- 9 Environmental Alteration of Insecticide Residues.- 9.1. Characteristics of Environmental Alteration.- 9.2. Characteristics of Microbial Metabolism.- 9.3. Metabolism of Chlorinated Hydrocarbon Insecticides by Microorganisms.- 9.3.1. DDT Analogues.- 9.3.2. BHC.- 9.3.3. Cyclodiene Insecticides.- 9.4. Metabolism of Organophosphate and Carbamate Insecticides by Microorganisms.- 9.5. Metabolism of Acaricidal Compounds by Microorganisms.- 9.6. Degradation by Sunlight and Other Physical Factors.- 9.6.1. Chlorinated Hydrocarbons.- 9.6.2. Aromatic Pesticides.- 9.7. References.- 10 Effects of Pesticides on Wildlife.- 10.1. General Survey of Residue Levels in Various Ecosystems.- 10.2. Hazards to Wildlife.- 10.2.1. Acute Toxicity.- 10.2.2. Chronic Toxicity.- 10.2.3. Factors Influencing Toxicity.- 10.2.3a. Age and Size.- 10.2.3b. Environmental Factors.- 10.2.4. Subtle Effects of Insecticides.- 10.2.4a. Birds.- 10.2.4b. Fish and Other Aquatic Organisms.- 10.3. Biological Transfer and Bioaccumulation.- 10.3.1. Route of Biological Transport.- 10.3.1a. General Pattern.- 10.3.1b. Aquatic Environments.- 10.3.1c. Terrestrial Environments.- 10.3.2. Bioaccumulation Through the Food Chain.- 10.3.2a. Aquatic Environments.- 10.3.2b. Terrestrial Environments.- 10.3.3. Factors Affecting the Degree of Bioaccumulation.- 10.3.3a. Physicochemical Characteristics of Insecticides.- 10.3.3b. Competition: “Biological Concentration” vs. “Biological Dilution”.- 10.3.3c. Rate of Food Consumption and Body Size.- 10.3.3d. Dynamics of Pesticide Bioaccumulation.- 10.4. References.- 11 Hazards to Man and Domestic Animals.- 11.1. Introduction.- 11.2. Acute Poisoning by Insecticidal Chemicals.- 11.2.1. Chlorinated Hydrocarbon Insecticides : General Group Characteristics and Method of Treatment.- 11.2.2. DDT Poisoning.- 11.2.2a. Animals.- 11.2.2b. Symptoms of DDT Poisoning in Animals.- 11.2.2c. Human Toxicology.- 11.2.3. BHC Poisoning.- 11.2.4. Aldrin and Dieldrin Poisoning.- 11.2.4a. Symptoms and Toxicity.- 11.2.4b. Autopsy Results on Dieldrin-Poisoned Animals.- 11.2.5. Organophosphate Poisoning.- 11.2.5a. Symptoms.- 11.2.5b. Cause of Death.- 11.2.5c. Example : Description of Malathion Poisoning.- 11.2.6. Carbamate Poisoning.- 11.2.6a. Symptoms and Treatment.- 11.2.6b. Example: Description of Carbofuran Poisoning.- 11.2.7. Botanical Insecticides.- 11.2.7a. Nicotine.- 11.2.7b. Rotenone.- 11.3. Chronic Toxicity and Studies on Subtle Effects.- 11.3.1. Studies on Occupational Exposure and Human Feeding Tests.- 11.3.1a. Chlorinated Hydrocarbon Insecticides.- 11.3.1b. Organophosphates and Carbamates.- 11.3.2. Nonfatal and Subtle Effects of Insecticides.- 11.3.2a. Pathological and Histological Changes.- 11.3.2b. Biochemical Changes.- 11.3.2c. Carcinogenicity-Tumorigenicity.- 11.3.2d. Mutagenicity and Teratogenicity.- 11.4. Insecticide Residues in Man.- 11.4.1. Geographical Variation in Residues Found in Man.- 11.4.2. Factors Influencing the Residue Levels in Man.- 11.4.3. The Meaning of Residues in Man.- 11.4.3a. Change in Residue Levels with Time.- 11.4.3b. Human Intake of Pesticides Through Residues.- 11.4.3c. Pharmacokinetics of Pesticide Residues in Man.- 11.4.3d. Assessment of Safety.- 11.5. References.- Author Index.