2,5-Hexanedione (2,5-HD) is believed to be the ultimate neurotoxic metabolite of the industrial neurotoxic solvents n-hexane and methyl-n-butyl ketone. Tri-o-cresyl phosphate (TOCP) is also a neurotoxic contaminant found in the commercial preparation tricresyl phosphate. These studies were initiated to investigate the absorption, distribution, excretion and metabolism of these neurotoxic chemicals in various species. It was also of interest to study the role of pharmacokinetics and metabolism in species sensitivity to neurotoxic agents. Analytical methods using capillary gas chromatography (GC) and high performance liquid chromatography (HPLC) were developed to analyze the parent compounds and their metabolites. Five metabolites of TOCP were synthesized and their structures were verified by various spectroscopic techniques. The metabolism of (14C)2,5-HD in the chicken was investigated following a dermal application of 50 mg/kg dose. The metabolism and disposition of TOCP was investigated following dermal application of (14C) labeled compound on the male cat. Also being investigated is the metabolism and disposition of orally administered TOCP to rats, cats and chickens.
