Organophosphorus insecticides which currently represent the most important class of biodegradable insecticides, are inherently reactive molecules. Alterations of tissue macromolecules by covalent bonding of these insecticides or their metabolites will be studied as the basis of potential health hazards. By using radiolabeled parathion, paraoxon and related organophosphates, this project examines certain vital functions that may be affected by the macromolecular binding of organophosphates, and analyzes the metabolic factors that influence such binding, especially dialkylphosphorylation of proteins and sulfur binding. In view of the demonstrated side effects (teratogenicity, neuropathy and interference with detoxication), various cellular regulatory mechanisms and drug metabolizing systems will be examined with emphasis. Rats will be used as the principal experimental animals, but mice and chickens will also be used when appropriate.