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
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...
importance of this disagreement stems from two facts:
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.
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.
two crucial studies are by Ashby
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.
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.
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
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"
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