Disposition, elimination, and metabolism of tri-o-cresyl phosphate following daily oral administration in Fischer 344 male rats.
Arch Toxicol 1990 Oct; 64(7):572-579
The role of the disposition, elimination and metabolism of daily doses of tri-o-cresyl-phosphate (78308) (TOCP) in male Fischer-344- rats in the development of testicular toxicity was investigated. Adult male rats were given carbon-14 labeled TOCP at 50mg/kg per day for a 10 day period. Rats were sacrificed at 24, 48, 72, or 96 hours after administration of the tenth dose. Neither signs of acute cholinergic nor delayed neurotoxic effects were seen. The daily doses were rapidly absorbed, distributed and eliminated. Concentrations of carbon-14 24 hours after the administration of the tenth dose were 35, 63, and 37 times those found 24 hours after a single dose in the brain, spinal cord, and sciatic nerve, respectively. A considerable amount of the carbon-14 in the brain of rats given ten doses of TOCP was identified as TOCP and its active metabolite saligenin-cyclic-o-tolyl-phosphate 1 day after the last dose. Only traces of these compounds were found 4 days later. The testis had 33 times the carbon-14 concentration in the daily dosed animals compared to rats given a single dose. The testis contained the highest concentration of any analyzed tissue of the metabolite saligenin-cyclic-o-tolyl-phosphate. Three possible pathways of metabolism for TOCP were suggested.
NIOSH-Publication; NIOSH-Grant; Metabolic-study; Laboratory-animals; Phosphates; Organo-phosphorus-compounds; Nervous-system-disorders; Neurotoxicity; Plasticizers; Reproductive-hazards
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Archives of Toxicology
Duke University, Durham, North Carolina