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Disposition of [14C]tri-o-cresyl phosphate and its metabolites in various tissues of the male cat following a single dermal application.

Authors
Nomier-AA; Abou-Donia-MB
Source
Drug Metab Dispos 1984 Nov; 12(6):705-711
NIOSHTIC No.
00232169
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Metabolic-study; Metabolites; Laboratory-animals; Skin-exposure; Organo-phosphorus-compounds
Contact
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
CODEN
DMDSAI
CAS No.
78-30-8; 1222-87-3
Publication Date
19841101
Document Type
Journal Article
Funding Amount
1567389.00
Funding Type
Grant
Fiscal Year
1985
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-00823
Issue of Publication
6
ISSN
0090-9556
Priority Area
Neurotoxic Disorders; Neurotoxic-effects
Source Name
Drug Metabolism and Disposition
State
NC
Performing Organization
Duke University, Durham, North Carolina
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