Lack of selective developmental neurotoxicity in rat pups from dams treated by gavage with chlorpyrifos

Pregnant Sprague-Dawley rats were given chlorpyrifos (O,O-diethyl-O-[3,5,6- trichloro-2-pyridinyl] phosphorothioate; CPF) in corn oil by gavage from ge station day 6 (GD 6) through lactation day 10 (LD 10) at dosages of 0, 0.3, 1, or 5 mg/kg/day in a developmental neurotoxicity study that conformed to U.S. Environmental Protection Agency 1991 guidelines. GD 0 was the day whe n evidence of mating was observed and postnatal day 0 (PND 0) was the day o f birth. Toxicity was limited to the highest dosage level (5 mg/kg/day) and , in the dams, consisted of muscle fasciculation, hyperpnea, and hyperreact ivity. A nonsignificant overall trend toward weight gain and feed consumpti on was also observed in the high-dosage dams, with a statistically signific ant Group x Time interaction for reduced weight gain in the 5-mg/kg/day gro up near the end of gestation. Although many developmental indices were norm al, pups from high-dosage dams had increased mortality soon after birth, ga ined weight more slowly than controls, and had several indications of sligh tly delayed maturation. The early deaths and delayed maturation were attrib uted to maternal toxicity, though a possible contributing role of direct pu p toxicity in delayed development cannot be eliminated. In spite of the app arent delay in physical development, high-dosage pups tested just after wea ning had normal learning and memory as tested on a T-maze spatial delayed-a lternation task. Habituation, a primitive form of learning, was tested in 2 tasks (motor activity and auditory startle) and was not affected. No overt effects were noted in either dams or pups at 1 or 0.3 mg/kg/day, Based on these data, chlorpyrifos produced maternal and developmental toxicity in th e 5-mg/kg/day-dosage group, There was no evidence of selective developmenta l neurotoxicity following exposure to chlorpyrifos.