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Reproductive toxicity of MCPA (4-chloro-2-methylphenoxyacetic acid) in the rat
E M Bellet1, B van Ravenzwaay, J Hellwig
1Chemical Consultants International, Inc, Overland Park, Kansas, USA. ccii@swbell.net
Abstract:
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 (F0 parents) for 10 weeks. F0 parents were then mated to produce a first litter (F1a), retained only until weaning, and were subsequently remated to produce a second litter, F1b. Groups of male and female F1b animals were then dosed as were their parents for 10 weeks postweaning, and the breeding was repeated to produce F2a and F2b animals. The study concluded with the F2b weanlings. MCPA was administered continuously throughout the study. Only minimal, non-treatment-related observations were noted, which included rhinorrhea (in both treated and control animals in the F0 generation) and malocclusion and alopecia (in both the F0 and F1b 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 F2a and F2b. 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 450 ppm (approximately 22 mg/kg/day). The NOEL for general systemic toxicity, based on body weight effects in adult animals in the F1b generation was 150 ppm. The NOEL for effects on the offspring of the F1b 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.
Insights
This study found that 4-chloro-2-methylphenoxyacetic acid (MCPA) did not cause reproductive toxicity in rats over two generations. The no-observable-effect level for reproductive function was 450 ppm, indicating MCPA is not a reproductive toxicant.
Area of Science:
- Toxicology
- Reproductive Toxicology
- Environmental Health
Background:
- 4-chloro-2-methylphenoxyacetic acid (MCPA) is a widely used herbicide.
- Assessing the reproductive effects of environmental chemicals is crucial for public health.
- Previous studies may not have fully evaluated multi-generational reproductive impacts.
Purpose of the Study:
- To evaluate the reproductive and developmental toxicity of MCPA in rats across two generations.
- To determine the no-observable-effect level (NOEL) for reproductive and systemic toxicity.
- To establish whether MCPA poses a risk to reproductive health.
Main Methods:
- Rats (F0 generation) were administered MCPA in their diet at doses of 0, 50, 150, or 450 ppm for 10 weeks prior to mating.
- Animals were mated to produce two litters (F1a and F1b), and F1b offspring were dosed and bred to produce F2a and F2b litters.
- Reproductive parameters, body weights, and macroscopic/microscopic findings were assessed throughout the two-generation study.
Main Results:
- No consistent dose-related effects on reproductive function were observed in parental or offspring generations.
- Minimal, non-treatment-related observations (e.g., rhinorrhea, malocclusion) occurred in both control and treated groups.
- Statistically significant reductions in pup body weight and weight gain were noted at the highest dose (450 ppm) in the F2 generation.
- The NOEL for reproductive function was 450 ppm; the NOEL for systemic toxicity and offspring effects was 150 ppm.
Conclusions:
- MCPA administered continuously for two generations did not exhibit reproductive toxicity in rats.
- The established NOELs indicate a margin of safety for reproductive and systemic effects.
- MCPA is considered not to be a reproductive toxicant based on this two-generation study.