CHEMICAL PESTICIDES: MODE OF ACTION AND TOXICOLOGY
CONTENTS CHAPTER INTRODUCTION MOTIVATION PESTICIDES AND OPINION THE ?Y IN THE SOUP LOW-TECH FOOD PRODUCTION CONCLUSION A GREAT MARKET THE NUMBER OF CHEMICALS USED AS PESTICIDES AMOUNTS OF PESTICIDES PRODUCED MARKETING DIRTY DOZENS NOMENCLATURE, DE?NITIONS, AND TERMINOLOGY TOXICOLOGY, ECOTOXICOLOGY, AND ENVIRONMENTAL TOXICOLOGY PESTICIDES, BIOCIDES, COMMON NAMES, CHEMICAL NAMES, AND TRADE NAMES CHEMICAL STRUCTURES ARE VERSATILE HELPFUL READING BIOCHEMISTRY AND CELL BIOLOGY GENERAL TOXICOLOGY INSECT BIOCHEMISTRY, PLANT PHYSIOLOGY, AND NEUROPHYSIOLOGY PESTICIDES SIDE EFFECTS OF PESTICIDES CHAPTER WHY IS A TOXICANT POISONOUS? SEVEN ROUTES TO DEATH ENZYME INHIBITORS DISTURBANCE OF THE CHEMICAL SIGNAL SYSTEMS TOXICANTS THAT GENERATE VERY REACTIVE MOLECULES THAT DESTROY CELLULAR COMPONENTS WEAK ORGANIC BASES OR ACIDS THAT DEGRADE THE PH GRADIENTS ACROSS MEMBRANES TOXICANTS THAT DISSOLVE IN LIPOPHILIC MEMBRANES AND DISTURB THEIR PHYSICAL STRUCTURE TOXICANTS THAT DISTURB THE ELECTROLYTIC OR OSMOTIC BALANCE OR THE PH STRONG ELECTROPHILES, ALKALIS, ACIDS, OXIDANTS, OR REDUCTANTS THAT DESTROY TISSUE, DNA, OR PROTEINS HOW TO MEASURE TOXICITY ENDPOINTS ENDPOINTS IN ECOTOXICOLOGY AND PEST CONTROL ENDPOINTS IN HUMAN TOXICOLOGY DOSE AND EFFECT DOSE AND RESPONSE DOSE–RESPONSE CURVES FOR THE STABLE ?Y SCATTER IN DOSE–RESPONSE DATA LD50 AND RELATED PARAMETERS ACUTE AND CHRONIC TOXICITY INTERACTIONS DE?NITIONS ISOBOLES MECHANISMS OF INTERACTIONS EXAMPLES PIPERONYL BUTOXIDE DELTAMETHRIN AND FENITROTHION ATRAZINE AND ORGANOPHOSPHATE INSECTICIDES PESTICIDES INTERFERING WITH PROCESSES IMPORTANT TO ALL ORGANISMS PESTICIDES THAT DISTURB ENERGY PRODUCTION ANABOLIC AND CATABOLIC PROCESSES SYNTHESIS OF ACETYL COENZYME A AND THE TOXIC MECHANISM OF ARSENIC THE CITRIC ACID CYCLE AND ITS INHIBITORS FLUOROACETATE INHIBITORS OF SUCCINIC DEHYDROGENASE THE ELECTRON TRANSPORT CHAIN AND PRODUCTION OF ATP ROTENONE INHIBITORS OF ELECTRON TRANSFER FROM CYTOCHROME B TO C1 INHIBITORS OF CYTOCHROME OXIDASE UNCOUPLERS INHIBITION OF ATP PRODUCTION ORGANOTIN COMPOUNDS DIAFENTHIURON SUMMARY HERBICIDES THAT INHIBIT PHOTOSYNTHESIS WEAK ORGANIC ACIDS FREE RADICAL GENERATORS D1 BLOCKERS UREA DERIVATIVES TRIAZINES INHIBITORS OF CAROTENE SYNTHESIS AMITROLE ACLONIFEN BE?UBUTAMID PROTOPORPHYRINOGEN OXIDASE INHIBITORS GENERAL SH REAGENTS AND FREE RADICAL GENERATORS MERCURY OTHER MULTISITE FUNGICIDES PERHALOGENMERCAPTANS ALKYLENEBIS(DITHIOCARBAMATE)S AND DIMETHYLDITHIOCARBAMATES FUNGICIDES WITH COPPER PESTICIDES INTERFERING WITH CELL DIVISION FUNGICIDES BENOMYL THIOFANATE-METHYL CARBENDAZIM THIABENDAZOLE DIETHOFENCARB HERBICIDES TRI?URALIN CARBETAMIDE PESTICIDES INHIBITING ENZYMES IN NUCLEIC ACID SYNTHESIS SPORULATION-INHIBITING FUNGICIDES INHIBITION OF INCORPORATION OF URIDINE INTO RNA BACILLUS THURINGIENSIS AND ITS TOXINS THE MECHANISM OF ACTION OF ?-ENDOTOXINS BIOTECHNOLOGY ENGINEERED PLANTS BIOLOGY COMMERCIAL PRODUCTS SPECI?C ENZYME INHIBITORS INHIBITORS OF ERGOSTEROL SYNTHESIS INHIBITION OF HMG-COA REDUCTASE INHIBITION OF SQUALENE EPOXIDASE DMI FUNGICIDES EXAMPLES OF DMI FUNGICIDES FROM EACH GROUP AZOLES AND TRIAZOLES PYRIDINES AND PYRIMIDINES PIPERAZINES AMINES MORPHOLINES CONCLUSIONS HERBICIDES THAT INHIBIT SYNTHESIS OF AMINO ACIDS THE MODE OF ACTION OF GLYPHOSATE DEGRADATION OF GLYPHOSATE SELECTIVITY MODE OF ACTION OF GLUFOSINATE INHIBITORS OF ACETOLACTATE SYNTHASE INHIBITORS OF CHITIN SYNTHESIS INSECTICIDES INHIBITORS OF CHOLINESTERASE ACETYLCHOLINESTERASE ORGANOPHOSPHATES NATURALLY OCCURRING ORGANOPHOSPHORUS INSECTICIDES CARBAMATES MOLECULAR STRUCTURE AND POTENCY OF INHIBITION DEVELOPMENT OF ORGANOPHOSPHORUS AND CARBAMATE INSECTICIDES PARATHION AND SIMILAR COMPOUNDS ALIPHATIC ORGANOPHOSPHATES EXAMPLES OF CARBAMATES OTHER ENZYMES INHIBITED BY ORGANOPHOSPHATES AND CARBAMATES THE BUTYRYLCHOLINESTERASES THE NEUROTOXIC TARGET ENZYME (NTE) CARBOXYLESTERASES INTERFERENCE WITH SIGNAL TRANSDUCTION IN THE NERVES POTENCY OF NERVE POISONS THE NERVE AND THE NERVE CELL PESTICIDES THAT ACT ON THE AXON IMPULSE TRANSMISSION ALONG THE AXON PYRETHROIDS DDT AND ITS ANALOGUES PESTICIDES ACTING ON SYNAPTIC TRANSMISSION INHIBITORY SYNAPSES LINDANE FIPRONIL CYCLODIENE INSECTICIDES AVERMECTINS THE CHOLINERGIC SYNAPSES ATROPINE NICOTINOIDS AND NEONICOTINOIDS CARTAP CALCIUM CHANNELS AS POSSIBLE TARGETS FOR INSECTICIDES PESTICIDES THAT ACT AS SIGNAL MOLECULES INSECT HORMONES INSECT ENDOCRINOLOGY JUVENILE HORMONE AMERICAN PAPER TOWELS JUVENILE HORMONE AGONISTS AS PESTICIDES ANTAGONISTS ECDYSONE PHYTO-ECDYSONES SYNTHETIC ECDYSTEROIDS USED AS INSECTICIDES AZADIRACHTIN BEHAVIOR-MODIFYING PESTICIDES PHEROMONES STRUCTURE–ACTIVITY RELATIONSHIPS ALARM AND TRAIL PHEROMONES AGGREGATION PHEROMONES PHEROMONES USED AS PESTICIDES AND LURES COLEOPTERA LEPIDOPTERA FRUIT ?IES APHID FOOD DETERRENT MOSQUITO REPELLENTS PLANT HORMONES TRANSLOCATION AND DEGRADATION OF PESTICIDES THE COMPARTMENT MODEL THE BIOCONCENTRATION FACTOR THE HALF-LIFE THE AREA UNDER THE CURVE EXAMPLE DISAPPEARANCE OF DIELDRIN IN SHEEP DIELDRIN UPTAKE IN SHEEP DEGRADATION OF PESTICIDES BY MICROORGANISMS DEGRADATION BY ADAPTION DEGRADATION BY CO-METABOLISM KINETICS OF DEGRADATION IMPORTANCE OF CHEMICAL STRUCTURE FOR DEGRADATION CO-METABOLISM AND ADAPTATION PARATHION AND OTHER PESTICIDES WITH NITRO GROUPS ESTER HYDROLYSIS OF CARBARYL MINERALIZATION OF DALAPON THE DEGRADERS SOIL ADSORPTION WHY ARE CHEMICALS ADSORBED? MEASUREMENTS OF ADSORPTION DESORPTION EVAPORATION BIOTRANSFORMATION IN ANIMALS OXIDATION EPOXIDE HYDROLASE GLUTATHIONE TRANSFERASE HYDROLASES GLUCORONOSYLTRANSFERASE AND SULFOTRANSFERASE STEREOSPECI?C BIOTRANSFORMATION DESIGNING PESTICIDES THAT HAVE LOW MAMMALIAN TOXICITY ACEPHATE MALATHION AND DIMETHOATE NEREISTOXIN RESISTANCE TO PESTICIDES RESISTANCE IS AN INEVITABLE RESULT OF EVOLUTION TIME FOR RESISTANCE DEVELOPMENT QUESTIONS ABOUT RESISTANCE ARE RESISTANT INSECTS MORE ROBUST THAN SENSITIVE ONES? IS RESISTANCE CAUSED BY ONE ALLELE IN ONE GENE LOCUS? DO PESTICIDES CAUSE RESISTANCE? BIOCHEMICAL MECHANISMS INCREASED DETOXICATION DDT DEHYDROCHLORINASE CYP ENZYMES IN INSECTS CYP ENZYMES IN PLANTS INSENSITIVE TARGET ENZYME OR TARGET RECEPTOR SITE KDR RESISTANCE RESISTANCE IN FUNGI BENZIMIDAZOLE STEROL BIOSYNTHESIS INHIBITORS ATRAZINE RESISTANCE AND PLANTS MADE RESISTANT BY GENETIC ENGINEERING RESISTANCE TO GLYPHOSATE RESISTANCE TO OLDER BIOCIDES USED AS PESTICIDES RESISTANCE TO THIRD- AND FOURTH-GENERATION PESTICIDES HOW TO DELAY DEVELOPMENT OF RESISTANCE REFUGE STRATEGY MIXING PESTICIDES WITH DIFFERENT MODES OF ACTION AND DIFFERENT DETOXICATION PATTERNS SWITCHING LIFE-STAGE TARGET INCREASED SENSITIVITY IN RESISTANT PESTS INHIBITION OF DETOXICATION ENZYMES 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 OF?CIAL APPROVAL OF A PESTICIDE 10 3 ANALYSIS OF RESIDUES IN FOOD AND THE ENVIRONMENT 10 3 1 DE?NITIONS 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 CLASSI?CATION OF PESTICIDES 10 4 1 1 CLASSI?CATION OF CARCINOGENECITY 10 4 2 DE?NITIONS 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