Reproductive toxicity of MCPA (4-chloro-2-methylphenoxyacetic acid) in the rat

The reproductive effects of the administration of 4-chloro-2-methylphenoxyacetic acid (MCPA) to rats were evaluated through two generations, from prior to mating, throughout mating, to gestation and lactation, MCPA was administered in the diet at doses of 0, 50, 150, or 450 ppm to 25 male and female immature rats (F-0 parents) for 10 weeks, F-0 parents were then mated to produce a first litter (F-1a), retained only until weaning, and were subsequently remated to produce a second litter, F-1b. Groups Of male and female F-1b animals were then dosed as were their parents for 10 weeks postweaning, and the breeding was repeated to produce F-2a and F-2b animals, The study concluded with the F-2b weanlings, MCPA was administered continuously throughout the study, Only minimal, non-treatment-related observations were noted, which included rhinorrhea tin both treated and control animals in the F-0 generation) and malocclusion and alopecia tin both the F-0 and F-1b generations), There were no consistent dose-related effects on reproductive function for parental animals of either sex in either generation, Statistically significant differences were noted in body weights and body weight gains in the 450-ppm dose group for both male and female pups in Fz, and F-2b There were no treatment-related macroscopic or microscopic observations noted for any animal in this study, The no-observable-effect level (NOEL) for reproductive function in rats administered MCPA continuously for two successive generations was determined to be 150 ppm (approximately 22 mg/kg/day), The NOEL for general systemic toxicity, based on body weight effects in adult animals in the F-1b generation was 150 ppm. The NOEL for effects on the offspring of the F-1b generation, manifested as reduced pup weights and pup weight gains was also 150 ppm (approximately 8 mg/kg/day), Based upon the results of this study, MCPA, administered for two generations to Crl:CD(SD)BR Albino rats, is considered not to be a reproductive toxicant.