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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.

Authors
Abou-Donia-MB; Nomeir-AA; Bower-JH; Makkawy-HA
Source
Toxicology 1990 Dec; 65(1):61-74
NIOSHTIC No.
00200378
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Grant; Organo-phosphorus-compounds; In-vivo-studies; Blood-plasma; Laboratory-animals; Biotransformation; Tissue-distribution; Mathematical-models; Pharmacodynamics; Metabolic-study
Contact
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
CODEN
TXCYAC
CAS No.
78-30-8
Publication Date
19901217
Document Type
Journal Article
Funding Amount
1567389
Funding Type
Grant
Fiscal Year
1991
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-00823
Issue of Publication
1
ISSN
0300-483X
Source Name
Toxicology
State
NC
Performing Organization
Duke University, Durham, North Carolina
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