Disposition of [14C]tri-o-cresyl phosphate and its metabolites in various tissues of the male cat following a single dermal application.
Drug Metab Dispos 1984 Nov; 12(6):705-711
Carbon-14 labeled tri-o-cresyl-phosphate (78308) (TOCP) was dermally applied to cats, and the disposition of TOCP and its metabolites was determined. The study examined this process in the brain, spinal cord, and sciatic nerve along with liver, kidneys, lungs and plasma of cats. Adult male cats received a single dermal dose of 50mg/kg and were sacrificed 0.5, 1, 2, 5, or 10 days after dosing. The highest plasma concentration of TOCP was recorded at 12 hours, with the metabolites peaking between 24 and 48 hours. TOCP had a half life of 1.2 days in the plasma and its disappearance followed a monoexponential kinetic. The major metabolites found in the plasma were di-o-cresyl-hydrogen-phosphate and o-cresyl-dihydrogen- phosphate. The dihydroxymethyl metabolite was noted in trace amounts. Saligenin-cyclic-o-tolyl-phosphate (1222873) was detected in the plasma at all times and is thought to be the active neurotoxic metabolite. The brain, spinal cord, and sciatic nerve contained predominantly TOCP itself. The liver, kidneys, and lungs contained primarily metabolites. The liver, kidneys and lungs contained o-hydroxybenzoic-acid as the major metabolite followed by di-o-cresyl-hydrogen-phosphate. The brain, spinal cord and sciatic nerve contained di-o-cresyl-hydrogen-phosphate and o-cresyl- dihydrogen-phosphate as the most predominant metabolites. Saligenin- cyclic-o-tolyl-phosphate was not found to any great degree due to its instability or high reactivity with many tissue enzymes.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Metabolic-study; Metabolites; Laboratory-animals; Skin-exposure; Organo-phosphorus-compounds
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Neurotoxic Disorders; Neurotoxic-effects
Drug Metabolism and Disposition
Duke University, Durham, North Carolina