Pharmacokinetics and metabolism of a single subneurotoxic oral dose of tri-o-cresyl phosphate in hens.
Hens were given a single oral dose of 50 mg (4.6 microCi)/kg [14C] tri-o-cresyl phosphate (TOCP). Four groups of three hens each were killed after 0.5, 1, 2, and 5 days. The half-life of 14C in plasma was 2 days. TOCP and its metabolites in the plasma, liver, kidneys, and lungs were analyzed by high-performance liquid chromatography and liquid scintillation counting. TOCP reached its highest concentration in plasma between 0.5 and 1 day after administration. Under these experimental conditions, the disappearance of TOCP from the plasma followed monoexponential kinetics with a half-life of 2.2 days. Appreciable concentrations of saligenin cyclic-o-tolyl phosphate, the active neurotoxic metabolite, were detected in the plasma as well as in the liver, kidneys, and lungs at all time points and had half-lives of 2.06, 1.36, 1.11 and 4.44 days, respectively. The presence of this active metabolite of TOCP might contribute to the sensitivity of the hen to TOCP-induced delayed neurotoxicity. Other hydrolytic and oxidative products of TOCP were also identified in tissues.
Suwita
E
E
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Abou-Donia
M B
MB
D000284:Administration, Oral; D000818:Animals; D002645:Chickens; D003408:Cresols / Q000493:pharmacokinetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D014317:Tritolyl Phosphates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D003408:Cresols; D014317:Tritolyl Phosphates; C025541:tri-o-cresyl phosphate