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


background on bisphenol A

Elsby, R, JL Maggs, J Ashby and BK Park. 2001. Comparison of the modulatory effects of human and rat liver microsomal metabolism on the estrogenicity of bisphenol A: implications for extrapolation to humans. Journal of Pharmacology and Experimental Therapeutics 297-103-113.

Elsby et al. show that rat experiments may underestimate the effects of bisphenol A on humans because of differences in the way that these two species metabolize the contaminant. Rats more efficiently convert BPA into a non-estrogenic metabolite than do humans. The human fetus shows even less ability to make this conversion, as the metabolic pathway responsible for conversion does not appear to develop until after birth.

What did they do?

Elsby et al. undertook a series of in vitro experiments using microsomes taken from human and rat livers. They exposed the preparations to bisphenol A and then examined the metabolites of BPA present following exposure, characterizing them with liquid chromatography-mass spectrometry and high performance liquid chromatography. Elsby et al. also determined the estrogenicity of the preparations after BPA exposure using a yeast estrogenicity assay.

What did they find?

BPA incubated with female rat livers yielded one major and two minor metabolites. Elsby et al. identified the major metabolite as the monoglucoronide of BPA, which is not estrogenic. One of the minor metabolites did demonstrate estrogenic activity, but at a lower level than BPA.

The preparation using human liver microsomes converted BPA to the glucuronide metabolite at a significantly lower rate than did the rat microsomes.

Examining the estrogenicity of the metabolized preparation using the yeast estrogenicity assay, they found that rat microsomes were more effective at reducing estrogenicity than human microsomes.

What do their findings mean?

According to the authors their results "suggest that assessment of the estrogenicity of BPA using the immature rat uterotrophic assay might well underestimate the potency of BPA in humans." This is an important finding given that this assay is a standard part of toxicity texting for estrogenic substances.




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