Distribution and metabolism of O-ethyl O-4-nitrophenyl phenylphosphonothioate after a single oral dose in one-week old chicks.

The toxicokinetics and metabolism of a single 1 mg (2.7 μCi/kg) oral dose of uniformly phenyl-labeled [14C]EPN (O-ethyl O-4-nitrophenyl [14C]phenylphosphonothioate) have been studied in 1-week old chicks. One control and three treated chicks were killed at each of the following time intervals: 0.5, 2, 4, 8, and 12 days. Radioactivity was rapidly absorbed from the gastrointestinal tract and distributed in all tissues. 14C in tissues reached a peak of 16.9% of the dose after 0.5 day and decreased to 0.6% at 4 days. The tissues of the gastrointestinal tract had the highest concentration of radioactivity, followed by bile and liver. Among nervous tissues, concentration of 14C was highest in the peripheral nerves. The spinal cord had the next highest concentration, while the brain had the least. After 4 days 91.3% of the 14C had been eliminated in the combined urinary-fecal excreta. By the end of the 12-day experiment this percentage reached 93.1%. No 14C was detected in the expired CO2. Following the oral administration of [14C]EPN, a monophasic body level curve was observed. The half-life for the elimination of 14C from chick body was 16 h, corresponding to a rate constant of 0.04 h−1. Most of the excreted 14C materials were identified as O-ethyl phenylphosphonic acid, phenylphosphonic acid, and O-ethyl phenylphosphonothioic acid.