title: Dose-response and time-course of neurobehavioral changes following oral chlorpyrifos in rats of different ages.
abstract: Young rats have been shown in several laboratories to be more sensitive to the neurotoxic effects of acute exposure to chlorpyrifos. To examine the neurobehavioral effects of chlorpyrifos as a function of age and dose, we conducted dose-response and time-course assessments in rats of three different ages (postnatal day, or PND, 17, 27, and adults). Doses were selected to span the effective dose range in each age group: PND17 - 4, 10, 20 mg/kg; PND27 - 10, 25, 50 mg/kg; adult - 10, 50, 100 mg/kg. Rats were tested at the time of peak effect on the day of dosing, and again at 1 and 3 days, and at 1 and 2 weeks after a single oral dose. There were age- and sex-related differences in the recovery of these behavioral effects; the adult males recovered from the behavioral effects more quickly than the other age groups, and the adult females showed the slowest recovery (up to at least 3 days). Although these doses had been shown previously to produce a similar degree of cholinesterase inhibition, the neurobehavioral alterations fell into the following three patterns of effect as a function of age. (1) Some endpoints (e.g., gait abnormalities, tremor) showed a dose-response curve that was shifted to the right in the older animals. Calculated ED50 values indicated that the PND17 rats were three- to five-fold more sensitive than the adults. (2) Some measures showed less effect in the youngest rats; for example, maximal motor activity decreases were half as great as with adults. (3) A few effects that were typically observed in adults, e.g., salivation, were not seen at all in the PND17 rats. Thus, differential responses on these neurobehavioral endpoints were observed as a function of age. These data suggest that, for some endpoints, young rats are more sensitive to a range of chlorpyrifos doses; however, the magnitude of age-related differences depends on the specific endpoint and time of assessment, as well as age and sex of the test subject.
authors: National Health and Environmental Effects Research Laboratory, Neurotoxicology Division (MD-74B), US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. moser.ginger@epamail.epa.gov
authors: V C
authors: VC
authors: Moser
mesh_terms: D000284:Administration, Oral; D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
chemical_list: D007306:Insecticides; D004390:Chlorpyrifos