Developmental toxicity of flupyrazofos, a new organophosphorus insecticide, in rats

Flupyrazofos is a new type of pyrazole organophosporus insecticide, which has a high activity against the diamond-back moth (Plutella xylostella). The potential of this agent to induce developmental toxicity was investigated in the Sprague-Dawley rat. One hundred mated females (sperm in vaginal LAVAGE=day 0) were distributed among three treated groups and a control group. Flupyrazofos was administered by gavage to pregnant rats from days 7-17 of gestation at dose levels of 0, 5, 12 and 30 mg/kg/day. All dams were subjected to the caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 30 mg/kg, maternal effects including mortality (4.3%), clinical signs of toxicity, decreased food intake, suppressed body weight, and increased weight of adrenal glands, kidney and heart were observed in dams. Litter values for corpora lutea, implantations, sex ratio and litter size were within the normal range. However, a reduction in the fetal weight and an increase in the incidence of fetal skeletal retardations were observed. At 12 mg/kg, toxic effects including mortality (4.2%), nasal discharge and some fetal skeletal retardation were observed. There were no signs of either maternal toxicity or embryotoxicity at 5 mg/kg. The results show that flupyrazofos induces fetal growth retardation only at maternally toxic doses in rats and the no-observed-adverse-effect levels (NOAELs) of this agent are considered to be 5 mg/kg for both dams and fetuses.