Developmental toxicity of a commercial herbicide mixture in mice: I. Effects on embryo implantation and litter size.

Abstract

We investigated the developmental toxicity in mice of a common commercial formulation of herbicide containing a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D), mecoprop, dicamba, and inactive ingredients. Pregnant mice were exposed to one of four different doses of the herbicide mixture diluted in their drinking water, either during preimplantation and organogenesis or only during organogenesis. Litter size, birth weight, and crown-rump length were determined at birth, and pups were allowed to lactate and grow without additional herbicide exposure so that they could be subjected to additional immune, endocrine, and behavioral studies, the results of which will be reported in a separate article. At weaning, dams were sacrificed, and the number of implantation sites was determined. The data, although apparently influenced by season, showed an inverted or U-shaped dose-response pattern for reduced litter size, with the low end of the dose range producing the greatest decrease in the number of live pups born. The decrease in litter size was associated with a decrease in the number of implantation sites, but only at very low and low environmentally relevant doses. Fetotoxicity, as evidenced by a decrease in weight and crown-rump length of the newborn pups or embryo resorption, was not significantly different in the herbicide-treated litters.

Developmental effects of herbicides in mice.

“…In Table 2 of our paper (Cavieres et al 2002), we showed that in all seasons every treatment group had fewer young than the control group. Only occasional points were statistically significant.…”

“…We concluded that most researchers will find only trends and not significant effects because treatment group sample sizes in individual experiments are too small. Lamb et al (2003) referred to discrepancies between our paper (Cavieres et al 2002) and the PhD thesis by Cavieres (2001). The analysis in our paper (Cavieres et al 2002) was performed on the original computer data files, which we consider to be the ultimate source.…”

“…Lamb et al (2003) referred to discrepancies between our paper (Cavieres et al 2002) and the PhD thesis by Cavieres (2001). The analysis in our paper (Cavieres et al 2002) was performed on the original computer data files, which we consider to be the ultimate source. The thesis (Cavieres 2001) was based on an earlier analysis of the data and contains many other measurements not included in our paper.…”

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

“…The dose spacing in this study was designed to address the low dose hypothesis proposed by Cavieres et al (2002). (The Cavieres et al research is summarized in Supplementary Appendix VII.)…”

“…Numbers of corpora lutea, implantation sites, resorptions and live embryos were similar between the dose groups and control. The Dinamarca et al study demonstrated that the finding of decreased implantations reported in mice exposed to 2,4-D by Cavieres et al (2002) could not be replicated, even with an exposure period correctly designed to explore this possibility. The only limitations we identified in the Dinamarca et al study was the failure to identify the specific purity of the "pure" test substance, and the lack of confirmatory dose analyses.…”