Toxicological Sciences 57, 250-263 (2000)
Copyright © 2000 by the Society of Toxicology
Neurotoxicology |
Lack of Selective Developmental Neurotoxicity in Rat Pups from Dams Treated by Gavage with Chlorpyrifos
* The Dow Chemical Company, Midland, Michigan 48674
Primedica, Argus Research Laboratories, Inc., Horsham, Pennsylvania 19044
CVP, Murrysville, Pennsylvania 15668–0068
§ Dow AgroSciences, LLC, Indianapolis, Indiana 46268
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 gestation 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 when evidence of mating was observed and postnatal day 0 (PND 0) was the day of birth. Toxicity was limited to the highest dosage level (5 mg/kg/day) and, in the dams, consisted of muscle fasciculation, hyperpnea, and hyperreactivity. A nonsignificant overall trend toward weight gain and feed consumption was also observed in the high-dosage dams, with a statistically significant Group x Time interaction for reduced weight gain in the 5-mg/kg/day group near the end of gestation. Although many developmental indices were normal, pups from high-dosage dams had increased mortality soon after birth, gained weight more slowly than controls, and had several indications of slightly delayed maturation. The early deaths and delayed maturation were attributed to maternal toxicity, though a possible contributing role of direct pup toxicity in delayed development cannot be eliminated. In spite of the apparent delay in physical development, high-dosage pups tested just after weaning had normal learning and memory as tested on a T-maze spatial delayed-alternation 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 the 5-mg/kg/day-dosage group. There was no evidence of selective developmental neurotoxicity following exposure to chlorpyrifos.
Key Words: chlorpyrifos; developmental neurotoxicity; spatial delayed alternation; motor activity; auditory startle; habituation; learning; memory; safety evaluation..
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