Disposition of [14C]tri-o-cresyl phosphate and its metabolites in various tissues of the male cat following a single dermal application.
The disposition and metabolism of a single dermal dose of 50 mg (5.8 muCi)/kg of tri-o-cresyl [phenyl-U-14C]phosphate (TOCP) were investigated in adult male cats. TOCP was applied on a preclipped area on the back of the animals neck. Three treated cats were sacrificed at each time interval 0.5, 1, 2, 5, and 10 days following application. Plasma, brain, spinal cord, sciatic nerve, liver, kidneys, and lungs were extracted and analyzed for TOCP and its various metabolites by high performance liquid chromatography and liquid scintillation counting. TOCP reached its highest concentration in plasma at 12 hr, while its metabolites attained their maximum concentration levels between 24 and 48 hr after dosing. The disappearance of TOCP from the plasma followed a monoexponential kinetics with a half-life of 1.2 days. Di-o-cresyl hydrogen phosphate and o-cresyl dihydrogen phosphate were the major metabolites in the plasma while dihydroxymethyl TOCP was present in trace amounts. Appreciable concentrations of saligenin cyclic-o-tolyl phosphate, which is believed to be the active neurotoxic metabolite, were detected in the plasma at all time points. TOCP was the predominant compound in the brain, spinal cord, and sciatic nerve, while the liver, kidneys, and lungs contained mostly metabolites. The major metabolite identified in the liver, kidneys, and lungs was o-hydroxybenzoic acid (salicylic acid) followed by di-o-cresyl hydrogen phosphate whereas di-o-cresyl hydrogen phosphate and o-cresyl dihydrogen phosphate were the most abundant metabolites in the brain, spinal cord, and sciatic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)
Nomeir, AA; Abou-Donia, MB
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