Tissue Distribution, Elimination, and Metabolism of O-Ethyl O-4-Nitrophenyl Phenylphosphonothioate in Hens Following Daily Dermal Doses

Abstract

The absorption, distribution, elimination, and metabolism of the insecticide O-ethyl O-4-nitrophenyl phenylphosphonothionate (EPN) were studied in the hen. A daily dermal dose of 0.5 mg/kg (0.56 μCi/dose) of [14C]EPN (O-ethyl O-4-nitrophenyl [14C] phenylphosphonothioate) was applied for 10 consecutive days to hens. Three treated hens were killed at each of the following time intervals: 1,5,10, and 15 days after the administration of the last dose. A total of 65% of the cumulative dose was excreted in the combined urinary and fecal excrement 15 days after the last dose. Small amounts of radioactivity were deposited in the egg yolk (0.8%) and the egg albumen (0.3%). No 14C02 was detected in the expired air. Radioactivity in the tissues reached a peak of 12% of the total administered dose one day after the last dose; 14C decreased to 1.5% of the total dose (12% of the peak value) 15 days after the administration of the last. dose. The concentration of radioactivity was highest in the liver, followed by the kidney, gall bladder, bile, small intestine, ceca, large intestine, and skin. Relatively low concentrations of 14C were detected in the central and peripheral nervous tissues. O-Ethyl phenylphosphonic acid (EPPA) was identified as the major urinary-fecal metabolite followed by phenylphosphonic acid (PPA) and O-ethyl phenylphosphonothioic acid (EPPTA). EPN accounted for most of the radioactivity in tissues except in the liver. In this tissue most of the radioactivity was identified as EPPA, EPPTA, and PPA.

Acute toxicity and metabolism of pesticides in birds

“…The same author's group has further compared the fate of [Ph- 14 C] EPN in hens with a single administration either orally by gavage or topically daily to skin at the bird's neck for 10 days at similar dosages. 130,131) Most of the dose (64-74%) was excreted by both administration types with the major 14 C residues present in the liver, kidney, and bile. Although the same metabolites were detected, the radioactivity in both non-conjugated and water-soluble fractions by the extraction of the excreta gradually increased as time passed after the single oral administration.…”

NIOSH skin notation (SK) profile: ethyl p-nitrophenyl phenylphosphorothioate (EPN) [CAS No. 2104-64-5].

“…When cats were administered 0.5 mg/ kg [ 14 C] EPN dermally for 10 consecutive days, 62% of the cumulative dose was recovered in the urine, 10% in the feces, and none in the expired air [Abou-Donia et al 1983e]. In hens administered 0.5 mg/kg (0.56 micro Curie per dose [μCi/dose]) of [ 14 C] EPN dermally for 10 consecutive days, a total of 65% of the cumulative dose was excreted in the combined urinary and fetal excrement 15 days after the last dose, and no radioactivity was detected in the expired air [Abou-Donia et al 1983a]. These toxicokinetic studies indicate that in cats and hens, EPN is absorbed through the skin following dermal exposure.…”