Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers


  Welshons, WV, KA Thayer, BM Judy, JA Taylor, EM Curran and FS vom Saal. 2003. Large effects from small exposures. I. Mechanisms for endocrine disrupting chemicals with estrogenic activity. Environmental Health Perspectives 111:994-1006.

Part II of this series

One of the larger controversies in endocrine disruption science has arisen because of industry failures to replicate work by vom Saal et al. finding that extremely low level exposures to bisphenol A during fetal development can lead to enlarged and hypersensitized prostates in mice. More on vom Saal's work...

The importance of this disagreement stems from two facts:

  • Traditional toxicology did not anticipate adverse effects of endocrine disrupting compounds at such low levels, in this case 2 ppb fed to the pregnant female. If effects at low levels were widely acknowledged, wholesale changes would be required in chemical regulation.
  • More specifically, bisphenol A is an extremely profitable compound. Studies from Germany and Japan make it now clear that many people carry serum levels of bisphenol A that are above those found by vom Saal and others a variety of developmental changes.

Industrial scientists have published in scientific meetings, reported at public meetings, and commented to the press that they cannot replicate effects at this level and that therefore no tightening of regulations about exposure to bisphenol A are warranted.

The two crucial studies are by Ashby et al. and Cagen et al. According to Welshons and his co-authors in this paper (of whom three were on the original vom Saal paper), a careful comparison of the vom Saal data with those of Ashby and Cagen reveals that the control animals in both these industry studies were obese and had enlarged prostates, and that in neither did the experimental group respond to either bisphenol A or the positive control, DES.

Welshons et al. here interpret Ashby and Cagen's failure to obtain a response to BPA or DES to be analogous to the experiment with estradiol plus DES reported in this paper: With 3 ppt of an estrogenic substance (DES) the low level response to estradiol which they obtained without estrogenic contamination was completed eliminated. They suggest that the enlarged prostates of Ashby and Cagen's control animals indicate estrogenic contamination, the presence of which eliminated the low level response to bisphenol A and DES.

It should be noted that a third industry study reported yet another failure to replicate vom Saal's work. A letter from the American Chemistry Council (a trade association representing the chemical industry) to the National Toxicology Program's (NTP) peer-review of low dose impacts, represents this paper as having found no effects of BPA on prostate weight at 0.005, 0.05, 0.5 or 5 mg/L drinking water (0.001 to 10 mg/kg/day)."

The NTP panel concluded in its report (p A-86), however, that in fact the study did find low dose alterations in prostate weight consistent with vom Saal et al: "The 0.05 mg/l [50 ppb] (p<0.01) the 5 mg/l [5 ppm] (p<0.0001) and the 50 mg/l [50 ppm] (p<0.02) were significantly increased relative to control." They also reported that hypothetical explanations offered by this paper and used to dismiss vom Saal's findings as false positives were "seriously flawed" and "illogical" (p A-90).

Nonetheless, industry continues to insist that low level effects of bisphenol A do not occur, e.g., on industry's bisphenol A website (accessed 11 March 2003). When does the liability clock for continued misrepresentation of science start ticking?






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