Studies on pesticides and related toxicants are designed to evaluate conditions for their safe and effective use, to develop better pesticides with improved selectivity, and to generate fundamental knowledge of general importance for the agricultural, medical and environmental sciences. Insecticide chemistry investigations emphasize synthesis and degradation of neurotoxicants including pyrethroids, isobutylamides and nitromethylene heterocycles and involve the identification and preparation of photoproducts and metabolites and the mechanisms of photodecomposition and photostabilization. Research on the toxicology of neuroactive insecticides considers the aforementioned neurotoxicants plus the polychlorocycloalkanes and trioxabicyclooctanes as to their labile sites and metabolic pathways, bioactivation and detoxification, interactions with antidotes and synergistic toxicants, and mode of action at neurophysiological and receptor levels. The goals in studies on organophosphorus acetylcholinesterase inhibitors are to resolve the chiral toxicants, examine the bioactivity of the individual enantiomers, recognize unusual bioactivation processes, identify the activation and detoxification reactions, and consider possible antidotes. Bicyclophosphorus esters, bicycloorthocarboxylates, polychlorocycloalkanes, and other cyclic or cage convulsants are used to investigate structure-activity relationships in their toxicity to mammals and insects and their potency in disrupting the gamma-aminobutyric acid-A receptor/chloride ionophore complex. Research on novel target sites considers: the binding site for the insecticide ryanodine relative to excitation-contraction coupling and the calcium-regulated calcium channel of the junctional region of the sarcoplasmic reticulum of mammalian muscle; compounds interfering with synthesis of chitin in insects; and herbicides and herbicide antidotes that alter amino acid biosynthesis in plants. Studies on hazardous pesticides focus on toxicants with halogen-, nitrogen-, sulfur- and oxygen-containing toxophoric groups. The goal is to provide a chemical explanation for their mutagenic, carcinogenic and hepatotoxic properties.
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