Distribution and metabolism of O-Ethyl O-4-nitrophenyl phenylphosphonothioate after a single oral dose in one-week old chicks.
Abou-Donia-MB; Hernandez-YM; Ahmed-NS; Abou-Donia-SA
Arch Toxicol 1983 Sep; 54(1):83-96
The metabolism and tissue distribution of O-ethyl-O-4-nitrophenyl- phosphonothioate (2104645) (EPN) were studied in chicks. One week old Leghorn-chicks were given 1mg/kg carbon-14 (C-14) labeled EPN orally. They had been pretreated with 15mg/kg atropine-sulfate to prevent cholinergic symptoms. Expired air, feces, and urine samples were collected periodically for 12 days and assayed for C-14 activity. Selected birds were killed 0.5, 2, 4, 8, or 12 days post dosing to determine the tissue distribution of EPN derived C-14 activity. The excreta and tissues were analyzed for EPN metabolites. No radioactivity was detected in the expired air. Cumulative urinary and fecal excretion of C-14 activity amounted to 91.3% of the dose after 4 days and 93.9% after 7 days. Total tissue EPN burdens peaked at 16.9% of the dose after 0.5 days and decreased to 0.6% of the dose after 4 days. Most of the radiolabel was found in the gastrointestinal tract contents at these time points. Smaller amounts were found in the bile and liver. Among the nervous tissues, the highest level of radioactivity was found in the peripheral nerves followed by the spinal cord and brain in that order. No radioactivity was detected in the gastrointestinal tract contents or tissues by day 12. Elimination of the total EPN body burden showed first order kinetics with a halflife of 16 hours. The authors conclude that following oral dosing to chicks, EPN is readily absorbed from the gastrointestinal tract and distributed to the tissues. The faster rate of metabolism and clearance of neurotoxic organophosphates in young animals may contribute to their resistance to organophosphate induced delayed neurotoxicity.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Tissue-distribution; Organo-phosphorus-compounds; In-vivo-studies; Laboratory-animals; Biotransformation; Pharmacodynamics
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Neurotoxic Disorders; Neurotoxic-effects
Archives of Toxicology
Duke University, Durham, North Carolina