Teratological assessment of trichlorphon in rats.

Trichlorphon was reported by Staples et al. (1976, 1979) and Martson and Voronina (1976) to have teratogenic effects in rats after gavage route of administration, but the teratogenic doses and treatment period listed by these authors are widely different. In the present study, trichlorphon was dissolved in deionized water or olive oil and administered by gavage consecutively once a day on days 8 through 15 of pregnancy at doses of 100, 200, 300 or 400 mg/kg, or once on day 13 at a dose of 400 mg/kg, in order to ascertain dose levels which affect the dams and fetuses. Control animals received the vehicle, deionized water or olive oil. On day 22 of pregnancy, the dams were killed and the fetuses were subjected to routine teratological examination. As a result, when administered consecutively, a significant decrease in maternal weight gain was observed at 300 mg/kg and above, regardless of the vehicles used. In addition, the maternal death occurred in approximately half the number of dams during the treatment period at 400 mg/kg. In fetal examinations, the incidence of skeletal anomalies was significantly higher at 300 mg/kg and above than in controls, and the incidences of external and visceral anomalies at 400 mg/kg. The major anomalies observed included clubbed limbs, fused vertebral arches, fused ribs, cleft palate and hydrocephaly. The minimum teratogenic doses and the types of fetal anomalies induced by trichlorphon were not affected by the two vehicles used. On the other hand, a single dose of 400 mg/kg, 5 times the dose level reported by Martson and Voronina, gavaged on day 13 of pregnancy produced neither maternal toxicity, nor fetal anomalies. In conclusion, the result of the present study was close to that of Staples et al. Trichlorphon was shown to induce teratogenic effects in rats at 300 mg/kg and above when administered by gavage consecutively on days 8 through 15 of pregnancy, correlated with dose levels that produced adverse maternal effects.