Implications for human health of the extensive bisphenol A literature showing adverse effects at low doses: a response to attempts to mislead the public.

Implications for human health of the extensive bisphenol A literature showing adverse effects at low doses: A response to attempts to mislead the public Bisphenol A is the chemical monomer used in the manufacture of resins that line cans, polycarbonate plastic (including many food and beverage containers), and as an additive in many other products. We respond here to an article published in Toxicology (202:1, 2004) entitled: " Fraud, errors and gamesmanship in experimental toxicology " by Dr. Iain Purchase in which he criticized research we had conducted on bisphenol A, a chemical that shows oestrogenic activity. Those who read the article by Dr. Purchase were led to believe that no studies had been published that confirmed our seminal publication concerning oestrogenic effects of very low doses of bisphenol A (Nagel et al., 1997). The presumed absence of any replications (by us or anyone else) of our low-dose study of bisphenol A led Dr. Purchase to identify our discussions of these findings as a form of " gamesmanship ". In reality, our article was the first of a very large number of published studies showing that bisphenol A has a wide range of adverse effects below the dose predicted to be safe for humans (the reference dose or tolerable daily intake). In the initial article by Nagel et al. (1997), we calculated that in vivo oestrogenic activity of bisphenol A in fetal mice would be detected at a 20 ␮g/kg/day dose of bisphenol A. This prediction had major public health implications in that the prediction was that bisphenol A should exhibit biological activity below the reference dose of 50 ␮g/kg/day. 1. our prior demonstration of very high potency of oestrogens during fetal development (vom Saal et al., 1997), and 2. our finding of limited binding of bisphenol A to oestrogen-binding proteins in human plasma, which results in a markedly elevated free plasma concentration of bisphenol A relative to oestradiol (Reviewed in: Nagel et al., 1999). Our calculations (that were described in detail in the initial article by Nagel) led us to propose that this very low (and presumably safe) maternal dose of bisphenol A would produce a change in development of the reproductive system (including a permanently enlarged prostate) in fetal mice that would be similar to effects reported in response to a very small increase in the endogenous hormone oestradiol and very low maternal doses of the potent oestrogenic …