Chemical pesticides : mode of action and toxicology

Chapter 1 Introduction 1.1 Motivation 1.2 Pesticides and opinion 1.2.1 The fly in the soup 1.2.2 Low-tech food production 1.2.3 Conclusion 1.3 A great market 1.3.1 The number of chemicals used as pesticides 1.3.2 Amounts of pesticides produced 1.3.3 Marketing 1.3.4 Dirty dozens 1.4 Nomenclature, definitions, and terminology 1.4.1 Toxicology, ecotoxicology, and environmental toxicology 1.4.2 Pesticides, biocides, common names, chemical names, and trade names 1.4.3 Chemical structures are versatile Helpful reading Biochemistry and cell biology General toxicology Insect biochemistry, plant physiology, and neurophysiology Pesticides Side effects of pesticides Chapter 2 Why is a toxicant poisonous? 2.1 Seven routes to death 2.1.1 Enzyme inhibitors 2.1.2 Disturbance of the chemical signal systems 2.1.3 Toxicants that generate very reactive molecules that destroy cellular components 2.1.4 Weak organic bases or acids that degrade the pH gradients across membranes 2.1.5 Toxicants that dissolve in lipophilic membranes and disturb their physical structure 2.1.6 Toxicants that disturb the electrolytic or osmotic balance or the pH 2.1.7 Strong electrophiles, alkalis, acids, oxidants, or reductants that destroy tissue, DNA, or proteins 2.2 How to measure toxicity 2.2.1 Endpoints 2.2.1.1 Endpoints in ecotoxicology and pest control 2.2.1.2 Endpoints in human toxicology 2.2.2 Dose and effect 2.2.3 Dose and response 2.2.3.1 Dose–response curves for the stable fly 2.2.3.2 Scatter in dose–response data 2.2.4 LD50 and related parameters 2.2.5 Acute and chronic toxicity 2.3 Interactions 2.3.1 Definitions 2.3.2 Isoboles 2.3.3 Mechanisms of interactions 2.3.4 Examples 2.3.4.1 Piperonyl butoxide 2.3.4.2 Deltamethrin and fenitrothion 2.3.4.3 Atrazine and organophosphate insecticides Chapter 3 Pesticides interfering with processes important to all organisms 3.1 Pesticides that disturb energy production 3.1.1 Anabolic and catabolic processes 3.1.2 Synthesis of acetyl coenzyme A and the toxic mechanism of arsenic 3.1.3 The citric acid cycle and its inhibitors 3.1.3.1 Fluoroacetate 3.1.3.2 Inhibitors of succinic dehydrogenase 3.1.4 The electron transport chain and production of ATP 3.1.4.1 Rotenone 3.1.4.2 Inhibitors of electron transfer from cytochrome b to c1 3.1.4.3 Inhibitors of cytochrome oxidase 3.1.4.4 Uncouplers 3.1.5 Inhibition of ATP production 3.1.5.1 Organotin compounds 3.1.5.2 Diafenthiuron 3.1.5.3 Summary 3.2 Herbicides that inhibit photosynthesis 3.2.1 Weak organic acids 3.2.2 Free radical generators 3.2.3 D1 blockers 3.2.3.1 Urea derivatives 3.2.3.2 Triazines 3.2.4 Inhibitors of carotene synthesis 3.2.4.1 Amitrole 3.2.4.2 Aclonifen 3.2.4.3 Beflubutamid 3.2.5 Protoporphyrinogen oxidase inhibitors 3.3 General SH reagents and free radical generators 3.3.1 Mercury 3.3.2 Other multisite fungicides 3.3.2.1 Perhalogenmercaptans 3.3.2.2 Alkylenebis(dithiocarbamate)s and dimethyldithiocarbamates 3.3.2.3 Fungicides with copper 3.4 Pesticides interfering with cell division 3.4.1 Fungicides 3.4.1.1 Benomyl 3.4.1.2 Thiofanate-methyl 3.4.1.3 Carbendazim 3.4.1.4 Thiabendazole 3.4.1.5 Diethofencarb 3.4.2 Herbicides 3.4.2.1 Trifluralin 3.4.2.2 Carbetamide 3.5 Pesticides inhibiting enzymes in nucleic acid synthesis 3.5.1 Sporulation-inhibiting fungicides 3.5.2 Inhibition of incorporation of uridine into RNA Chapter 4 Bacillus thuringiensis and its toxins 4.1 The mechanism of action of ن-endotoxins 4.2 Biotechnology 4.3 Engineered plants 4.4 Biology 4.5 Commercial products Chapter 5 Specific enzyme inhibitors 5.1 Inhibitors of ergosterol synthesis 5.1.1 Inhibition of HMG-CoA reductase 5.1.2 Inhibition of squalene epoxidase 5.1.3 DMI fungicides 5.1.4 Examples of DMI fungicides from each group 5.1.4.1 Azoles and triazoles 5.1.4.2 Pyridines and pyrimidines 5.1.4.3 Piperazines 5.1.4.4 Amines 5.1.4.5 Morpholines 5.1.5 Conclusions 5.2 Herbicides that inhibit synthesis of amino acids 5.2.1 The mode of action of glyphosate 5.2.2 Degradation of glyphosate 5.2.3 Selectivity 5.2.4 Mode of action of glufosinate 5.2.5 Inhibitors of acetolactate synthase 5.3 Inhibitors of chitin synthesis 5.3.1 Insecticides 5.3.2 Fungicides 5.4 Inhibitors of cholinesterase 5.4.1 Acetylcholinesterase 5.4.2 Organophosphates 5.4.2.1 Naturally occurring organophosphorus insecticides 5.4.3 Carbamates 5.4.3.1 Molecular structure and potency of inhibition 5.4.4 Development of organophosphorus and carbamate insecticides 5.4.4.1 Parathion and similar compounds 5.4.4.2 Aliphatic organophosphates 5.4.4.3 Examples of carbamates 5.5 Other enzymes inhibited by organophosphates and carbamates 5.5.1 The butyrylcholinesterases 5.5.2 The neurotoxic target enzyme (NTE) 5.5.3 Carboxylesterases Chapter 6 Interference with signal transduction in the nerves 6.1 Potency of nerve poisons 6.2 Selectivity 6.3 The nerve and the nerve cell 6.4 Pesticides that act on the axon 6.4.1 Impulse transmission along the axon 6.4.2 Pesticides 6.4.3 Pyrethroids 6.4.4 DDT and its analogues 6.5 Pesticides acting on synaptic transmission 6.5.1 Inhibitory synapses 6.5.2 Pesticides 6.5.2.1 Lindane 6.5.2.2 Fipronil 6.5.2.3 Cyclodiene insecticides 6.5.2.4 Avermectins 6.5.3 The cholinergic synapses 6.5.3.1 Atropine 6.5.3.2 Nicotinoids and neonicotinoids 6.5.3.3 Cartap 6.5.4 Calcium channels as possible targets for insecticides 6.6 Summary Chapter 7 Pesticides that act as signal molecules 7.1 Insect hormones 7.1.1 Insect endocrinology 7.1.2 Juvenile hormone 7.1.2.1 American paper towels 7.1.2.2 Juvenile hormone agonists as pesticides 7.1.2.3 Antagonists 7.1.3 Ecdysone 7.1.3.1 Phyto-ecdysones 7.1.3.2 Synthetic ecdysteroids used as insecticides 7.1.3.3 Azadirachtin 7.2 Behavior-modifying pesticides 7.2.1 Definitions 7.2.2 Pheromones 7.2.3 Structure–activity relationships 7.2.3.1 Alarm and trail pheromones 7.2.3.2 Aggregation pheromones 7.2.4 Pheromones used as pesticides and lures 7.2.4.1 Coleoptera 7.2.4.2 Lepidoptera 7.2.4.3 Fruit flies 7.2.4.4 Aphid food deterrent 7.2.4.5 Mosquito repellents 7.5 Plant hormones Chapter 8 Translocation and degradation of pesticides 8.1 The compartment model 8.1.1 The bioconcentration factor 8.1.2 The half-life 8.1.3 The area under the curve 8.1.4 Example 8.1.4.1 Disappearance of dieldrin in sheep 8.1.4.2 Dieldrin uptake in sheep 8.2 Degradation of pesticides by microorganisms 8.2.1 Degradation by adaption 8.2.2 Degradation by co-metabolism 8.2.3 Kinetics of degradation 8.2.4 Importance of chemical structure for degradation 8.2.5 Examples 8.2.5.1 Co-metabolism and adaptation 8.2.5.2 Parathion and other pesticides with nitro groups 8.2.5.3 Ester hydrolysis of carbaryl 8.2.5.4 Mineralization of dalapon 8.2.6 The degraders 8.3 Soil adsorption 8.3.1 Why are chemicals adsorbed? 8.3.2 Examples 8.3.2.1 Measurements of adsorption 8.3.3 Desorption 8.4 Evaporation 8.4.1 Example 8.5 Biotransformation in animals 8.5.1 Oxidation 8.5.2 Epoxide hydrolase 8.5.3 Glutathione transferase 8.5.4 Hydrolases 8.5.5 Glucoronosyltransferase and sulfotransferase 8.5.6 Stereospecific biotransformation 8.6 Designing pesticides that have low mammalian toxicity 8.6.1 Acephate 8.6.2 Malathion and dimethoate 8.6.3 Nereistoxin Chapter 9 Resistance to pesticides 9.1 Definitions 9.2 Resistance is an inevitable result of evolution 9.2.1 Time for resistance development 9.2.2 Questions about resistance 9.2.2.1 Are resistant insects more robust than sensitive ones? 9.2.2.2 Is resistance caused by one allele in one gene locus? 9.2.2.3 Do pesticides cause resistance? 9.3 Biochemical mechanisms 9.3.1 Increased detoxication 9.3.1.1 DDT dehydrochlorinase 9.3.1.2 Hydrolases 9.3.1.3 CYP enzymes in insects 9.3.1.4 CYP enzymes in plants 9.3.2 Insensitive target enzyme or target receptor site 9.3.2.1 Acetylcholinesterase 9.3.2.2 kdr resistance 9.3.3 Resistance in fungi 9.3.3.1 Benzimidazole 9.3.3.2 Sterol biosynthesis inhibitors 9.3.4 Atrazine resistance and plants made resistant by genetic engineering 9.3.5 Resistance to glyphosate 9.3.5.1 Summary 9.3.6 Resistance to older biocides used as pesticides 9.3.7 Resistance to third- and fourth-generation pesticides 9.4 How to delay development of resistance 9.4.1 Refuge strategy 9.4.2 Mixing pesticides with different modes of action and different detoxication patterns 9.4.3 Switching life-stage target 9.4.4 Increased sensitivity in resistant pests 9.4.5 Inhibition of detoxication enzymes 9.5 Conclusions Chapter 10 Pesticides as environmental hazards 10.1 Pesticides are poisons 10.1.1 Pesticides are xenobiotics 10.1.2 Various types of bias 10.1.2.1 Publication bias 10.1.2.2 Test bias 10.1.2.3 Extrapolation bias 10.1.3 Benchmark values 10.2 Required toxicological tests for official approval of a pesticide 10.3 Analysis of residues in food and the environment 10.3.1 Definitions 10.3.2 Sampling 10.3.3 Sample preparation 10.3.4 Analysis 10.3.4.1 Chromatographic methods 10.3.4.2 Biological methods 10.4 Pesticide residues in food 10.4.1 Toxicity classification of pesticides 10.4.1.1 Classification of carcinogenecity 10.4.2 Definitions of ADI and NOEL and tolerance limits 10.4.2.1 ADI 10.4.2.2 NOEL 10.4.2.3 Residue tolerance limits 10.4.3 Comparing health hazards of pesticides with other toxicants present in the market basket 10.5 Elixirs of death 10.5.1 Nomenclature and structure of dioxins 10.5.2 Dioxins in pesticides 10.5.2.1 Vietnam 10.5.2.2 Presence of dioxins in pesticides in general 10.5.3 Toxicology 10.5.4 The target 10.5.4.1 Dioxin and metabolism of caffeine 10.5.5 Analysis 10.5.5.1 Saturday, 12:30, July 10, 1976 10.5.6 Summary 10.6 Angry bird-watchers, youth criminals, and impotent rats 10.6.1 Clear Lake 10.6.2 Peregrine falcons and other birds of prey 10.6.2.1 Borlaug’s warning 10.6.2.2 DDT and impotence? 10.7 Conclusions