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Relevance of Reported Chromosomal Effects to Humans Has Not Been Established

April 1, 2003

Summary

A new paper in Current Biology reports that exposure to Bisphenol A (BPA) causes a chromosomal abnormality in the oocytes of female mice and might be read to suggest that the abnormality could lead to reproductive or developmental effects. However, reproductive and developmental effects were not examined in the new study and the experimental system used has not been validated or standardized for the evaluation of reproductive effects. Indeed, the authors of the study note that the relevance of the reported results to human health has not been established. The potential for BPA to cause reproductive or developmental effects has been comprehensively examined in two multi-generation studies. In these studies BPA did not cause reproductive or developmental effects at any environmentally relevant dose. The weight of scientific evidence provided by these studies, as well as others that have looked specifically at reproductive or developmental effects, clearly supports the safety of BPA and provides strong reassurance that there is no basis for human health concerns from exposure to environmentally relevant doses of BPA.

Relevance of Reported Chromosomal Effects to Humans Not Established

A new paper published today in Current Biology¹ reports that BPA causes a chromosomal abnormality known as meiotic aneuploidy in the oocytes of female mice. As noted in the paper, aneuploidy commonly occurs in humans and is considered to be the leading cause of miscarriage, congenital defects and mental retardation. Maternal age is known to have a potent effect on aneuploidy. Various potential environmental risk factors have also been suggested, including exposure to environmental chemicals. However, significant effects from environmental factors have been small and difficult to verify or disputed, making positive associations hard to establish.

Although the paper might be read to suggest that BPA or other environmental chemicals could have an effect on reproduction or development, no direct evidence to support this suggestion is reported in the paper since the experimental results did not examine reproduction or development. Indeed, as noted by the authors, additional research is needed to determine if their experimental system might provide a sensitive, reliable, and reproducible assay system for the evaluation of reproductive toxins. At this point, the experimental system has not been validated or standardized for use in assessing potential risk to human health. Consequently, as further noted by the authors, the relevance of the reported results to humans has not been established.

Environmentally Relevant Doses of BPA Do Not Cause Reproductive or Developmental Effects

Since the Hunt et al. study did not examine reproduction or development in their laboratory animals, additional research is needed to determine if the reported chromosomal abnormalities actually lead to functional effects. Although not referenced in the paper, extensive research has already been conducted to answer precisely this question.

Most notably, this includes a three-generation reproduction and development study on BPA conducted at the Research Triangle Institute under the direction of Dr. Rochelle Tyl ² , which is one of the most comprehensive studies of its kind ever conducted. In this study, Sprague-Dawley rats were fed a diet containing BPA at levels lower than those tested by Hunt et al. and ranging to levels more than a thousand times higher. A wide range of endpoints was examined to determine if BPA had any effect on the reproductive performance of the animals or on the development of the offspring. Analysis of the data for all of the endpoints for the parental and three offspring generations revealed no evidence for reproductive or developmental effects at any environmentally relevant dose. This exceptionally powerful study, which complied with Good Laboratory Practice standards and was conducted in accordance with internationally accepted guidelines, provides a definitive conclusion that BPA does not cause reproductive or offspring effects at low doses. Additional information on this study is available at http://www.bisphenol-a.org/development/whatsNew/20020702DefinitivePeer.html.

The results of a similar two-generation study commissioned by the Japanese National Institute of Health Sciences fully support the conclusions of the three-generation study.³ In this study, which also covered doses ranging from below to above the doses tested by Hunt et al., no effects on reproduction or development were found at any dose. In addition, this study also examined the offspring in two behavioral tests, including a learning test, and found no effects from exposure to BPA at any dose.

In addition, the results of a continuous breeding study in mice, conducted by the U.S. National Toxicology Program⁴, showed no effects on reproduction at a dose approximately 1000 times higher than the highest dose tested by Hunt et al.

Conclusion

The weight of scientific evidence provided by these studies clearly supports the safety of BPA and provides strong reassurance that there is no basis for human health concerns from exposure to environmentally relevant doses of BPA. Additional information on the weight of evidence is available at http://www.bisphenol-a.org/pdf/LowDoseUnprovenOctober2002.pdf (33kb, PDF).

Consistent with this conclusion, the use of polycarbonate plastic and epoxy resins for food contact applications has been and continues to be recognized as safe by the U.S. Food and Drug Administration, the European Commission Scientific Committee on Food, the United Kingdom Food Standards Agency, the Japanese Ministry for Health, Labor and Welfare, and other regulatory authorities worldwide.

1. "Bisphenol A Exposure Causes Meiotic Aneuploidy in the Female Mouse", P. A. Hunt, K. E. Koehler, M. Susiarjo, C. A. Hodges, A. Ilagen, R. C. Voigt, S. Thomas, B. F. Thomas, and T. J. Hassold, Current Biology (2003), 13:546-553.

2 "Three-Generation Reproductive Toxicity Study of Dietary Bisphenol A in CD Sprague-Dawley Rats", R. W. Tyl, C. B. Myers, M. C. Marr, B. F. Thomas, A. R. Keimowitz, D. R. Brine, M. M. Veselica, P. A. Fail, T. Y. Chang, J. C. Seely, R. L. Joiner, J. H. Butala, S. S. Dimond, S. Z. Cagen, R. N. Shiotsuka, G. D. Stropp, and J. M. Waechter, Toxicol. Sci. (2002) 68 (1): 121-146.

3 "Rat two-generation reproductive toxicity study of bisphenol A", M. Ema, S. Fujii, M. Furukawa, M. Kiguchi, T. Ikka, and A. Harazono, Reproductive Toxicology (2001), 15:505-523.

4 "Bisphenol A: Reproduction and Fertility Assessment in CD-1 Mice When Administered in the Feed", NTP Report No. RACB 84080. Information this study is available on the Internet at http://ntp-server.niehs.nih.gov/htdocs/RT-studies/RACB84080.html.