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Absorption, distribution, excretion and metabolism of a single oral dose of [14C]tri-o-cresyl phosphate (TOCP) in the male rat.
Abou-Donia MB; Nomeir AA; Bower JH; Makkawy HA
Toxicology 1990 Dec; 65(1):61-74
The distribution, excretion, and metabolism of tri-o-cresyl- phosphate (78308) (TOCP) were studied in rats. Male Sprague-Dawley- rats were given 50mg/kg carbon-14 (C-14) labeled TOCP orally. Urine, feces, and expired air were assayed for C-14 activity. Selected rats were killed 2, 6, or 12 hours or 1, 2, or 5 days after dosing to determine the tissue distribution of radiolabel. The plasma C-14 data were subjected to kinetic analysis. Plasma, liver, urine, and feces samples were analyzed for TOCP metabolites. TOCP was rapidly absorbed, TOCP derived C-14 activity being detected in all tissues within 2 hours of dosing. During the first 12 hours, most C-14 activity was found in the gastrointestinal tract and contents, plasma, urinary bladder, and liver. The least C-14 activity was found in the brain, spinal cord, muscles, and testes. Most tissue C-14 concentrations plateaued after 6 to 12 hours, decreasing thereafter. After 5 days, the highest C-14 concentrations were found in the liver, erythrocytes, skin, kidney, and lungs. Among the neural tissues, the most C-14 activity was found in the sciatic nerve. Approximately 63 and 36% of the dose was excreted in the urine and feces after 5 days, respectively. Very little C-14 activity was detected in the expired air. The decrease in activity in the plasma could be fitted to a two component exponential equation with a terminal halflife of 46 hours. Metabolites found in the plasma, liver, urine, and feces were identified. The authors conclude that after oral dosing TOCP is rapidly absorbed and distributed throughout the body and efficiently eliminated in male rats. The rapid metabolism and elimination of TOCP may be responsible, at least in part, for the lack of sensitivity of rats to organophosphate induced delayed neurotoxicity.
NIOSH-Publication; NIOSH-Grant; Organo-phosphorus-compounds; In-vivo-studies; Blood-plasma; Laboratory-animals; Biotransformation; Tissue-distribution; Mathematical-models; Pharmacodynamics; Metabolic-study; Author Keywords: Tri-o-cresyl phosphate; Organophosphorus compound-induced delayed neurotoxicity; Metabolism; Rat; Delayed neurotoxicity
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Issue of Publication
Duke University, Durham, North Carolina
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