The candidate, Dr. Janice Chambers, intends to develop a career in biochemical toxicology, with emphasis on insecticide mechanisms of action and metabolism, and other related aspects of neurotoxicology, such as behavior. The current emphasis is on concepts related to the acute toxicity of organophosphorus insecticides, which act by inhibiting acetylcholinesterase (AChE). Her short term career goal is to establish a more productive program in metabolism of organophosphorus insecticides and toxic interactions of these compounds in the organism. Her long term career goal is to establish a recognized research program in insecticide neurotoxicology, with emphasis on mechanisms of action (including metabolism) in vertebrates. The proposed RCDA would reduce current teaching commitments of two courses per semester to two courses per year and likewise reduce committee assignments so that the candidate will be able to devote a far greater percentage of her time to research. This concentration will allow her the time not previously available to learn new methodologies to expand the scope of her research program into logical related areas, to better keep up with new developments in the field, to interact more effectively with her graduate students, and to write manuscripts on completed research results. Mississippi State University will reduce her annual teaching load to two courses in her field (Toxicology and Principles of Toxicology) and will reduce her committee obligations to service on only the Animal Research Committee. The research project to be conducted during the tenure of the RCDA will be an investigation of the monooxygenase-mediated activation and detoxication of phosphorothionate insecticides and the detoxication of the activated metabolites by brain (the target tissue) and liver, along with the potential mechanisms (esterases and other binding proteins) present in liver and blood which would protect the target AChE. This current project (ES 04394) will be expanded later into the areas of structure-activity relationships, toxicokinetics and enzyme kinetics.