Tissue distribution, elimination, and metabolism of O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens following daily dermal doses.
Abou-Donia-MB; Abdel-Kader-HM; Abou-Donia-SA
J Amer Coll Toxicol 1983 Nov/Dec; 2(6):391-404
The absorption, tissue distribution, elimination, and metabolism of daily dermal small doses of carbon-14 labeled O-ethyl-O-4- nitrophenyl-phenylphosphonothioate (2104645) (EPN) were investigated in leghorn-hens. Three hens were treated with five daily dermal doses of EPN and then killed 1 day after the last dose in a preliminary experiment. In the main study, 12 hens were given ten daily dermal doses of 0.5mg/kg EPN. Hens were killed at 1, 5, 10, or 15 days after the tenth dose was administered. Hens treated with ten consecutive daily dermal doses of 0.5mg/kg EPN did not develop cholinergic or delayed neurotoxic effects. Administered in small daily doses, the EPN was efficiently absorbed, as indicated by the disappearance of radioactivity from the application site, disposition of carbon-14 in the tissues, and its excretion. No radioactivity was noted in the expired air. The findings indicated that the phenyl ring in the phenylphosphonothioate moiety of EPN was not completely degraded in the hen. The study confirmed the suggestion that pharmacokinetics and metabolism of organophosphorus compounds may contribute, at least in part, to species sensitivity to organophosphorus-induced delayed neurotoxicity.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Metabolic-study; Laboratory-animals; Body-burden; Organo-phosphorus-pesticides; Agricultural-chemicals; Nervous-system-disorders; Insecticides
Mohamed B. Abou-Donia, Department of Pharmacology, Duke University Medical Center, Durham, NC 27710
Journal of the American College of Toxicology
Duke University, Durham, North Carolina