The absorption, distribution, excretion, and metabolism of a single oral dose of O-ethyl O-4-nitrophenyl phenylphosphonothioate in hens.
Abou-Donia-MB; Reichert-BL; Ashry-MA
Toxicol Appl Pharmacol 1983 Aug; 70(1):18-28
The pharmacokinetics and metabolism of a single oral 10mg/kg dose of carbon-14 labeled O-ethyl-O-4-nitrophenyl-phenylphosphonothioate (2104645) (EPN) were investigated in mature laying hens. Atropine- sulfate was administered immediately before EPN to protect the hens from acute toxicity. A single 10mg/kg dose was administered in a gelatine capsule. Hens were maintained in metabolism chambers. Hens were sacrificed at 0.5, 2, 4, 8, or 12 days after dosing. Most (74%) of the dose was excreted in the combined urinary and fecal excreta. Traces of radioactivity, 0.2%, were detected in expired carbon-dioxide. Most of the radioactive materials which were excreted were identified as phenylphosphonic-acid (1571331), O-ethyl- phenylphosphonic-acid, and O-ethyl-phenylphosphonothioic-acid. By 12 days after dosing, radioactivity in tissues reached a peak at 11.8%. The liver had the highest concentration of radioactivity, followed by the bile, kidney, adipose tissue, and muscle. The major compound identified in the brain, spinal cord, sciatic nerve, kidney and plasma was EPN. The half life of the elimination of EPN from plasma was 16.5 days, corresponding to a constant rate value of 0.04/day. This study indicated that a single oral toxic dose of EPN has a long elimination half life and exhibits high relative residence of EPN in tissues relative to plasma. The authors conclude that pharmacokinetics and metabolism of organophosphorus compounds may be important in species selectivity to organophosphorus ester induced delayed neurotoxicity.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Laboratory-animals; Metabolic-study; Tissue-distribution; Body-burden; Organo-phosphorus-pesticides; Agricultural-chemicals; Nervous-system-disorders
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Neurotoxic Disorders; Neurotoxic-effects
Toxicology and Applied Pharmacology
Duke University, Durham, North Carolina