Evaluation of the developmental and reproductive toxicity of chlorpyrifos in the rat

Chlorpyrifos (O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)-phosphorothioate), an organophosphate insecticide, was evaluated for its potential to produce developmental and reproductive toxicity in rats following oral exposure. Pregnant Fischer 344 rats were given doses of 0 (corn oil vehicle), 0.1, 3.0, or 15 mg chlorpyrifos/kg/day, by gavage, on Gestation Days 6 through 15. Maternal effects noted at the two higher dose levels included decreased cholinesterase levels at 3.0 mg/kg/day and cholinergic signs (excessive salivation and tremors), decreased cholinesterase levels, and decreased body weight gain at 15 mg/kg/day. No maternal effects were apparent at 0.1 mg/kg/day. Although maternal toxicity was observed at these two higher exposure levels, no developmental effects were noted at any dose. In a two-generation reproduction study, Sprague-Dawley rats were maintained on diets supplying 0, 0.1, 1.0, or 5.0 mg chlorpyrifos/kg/day. Parental effects included decreased plasma and erythrocyte cholinesterase at 1.0 mg/kg/day, and decreased plasma, erythrocyte, and brain cholinesterase and histopathologic alterations of the adrenal zona fasciculata at 5.0 mg/kg/day. The histopathologic alterations of the adrenal were characterized as very slight to slight vacuolation (consistent with fatty change) in males, and very slight vacuolation and/or altered tinctorial properties in females. No effects on the reproductive or fertility indices or on the histopathology of reproductive tissues were observed at any dose level, and no neonatal effects were observed at 0.1 or 1.0 mg/kg/day in the F1 or F2 litters. Parental toxicity at the high dose was accompanied by decreased pup body weight and increased pup mortality in the F1 litters only. These data show that oral administration of chlorpyrifos to rats at parentally toxic dose levels was not embryolethal, embryo/fetotoxic, or teratogenic and did not adversely affect fertility or the function or structure of the reproductive organs. Although effects on neonatal growth and survival were observed at a maternally toxic dose level in one generation, this effect was not observed in the subsequent generation and, therefore, may not have been related to treatment.