An article published on March 1, 2017 in the peer-reviewed journal Nature Communications reports on the occurrence and endocrine disrupting effects of a chemical used as a substitute for bisphenol A (BPA, CAS 80-05-7). Zhaobin Zhang and colleagues from the College of Urban and Environmental Sciences, Peking University, Beijing, China, studied fluorene-9-bisphenol (BHPF, also called 9,9-bis(4-hydroxyphenyl)fluorene, CAS 3236-71-3). This chemical is used in the synthesis of ‘BPA-free’ polycarbonate plastics, epoxy resins, polyurethanes, polyesters, polyarylates, and polyethers.

The scientists found that BHPF has anti-estrogenic effects (blocking of estrogen receptor), both in vitro (in cell-based assays) and in vivo (in mice). The anti-estrogenic action of BHPF is opposite to what BPA normally does (BPA is estrogenic, i.e. it activates the estrogen receptor). Nonetheless, BHPF’s interference with the body’s hormone signaling may prove no less harmful, as BHPF-exposed mice, compared with unexposed animals, were found to have smaller wombs and a higher rate of miscarriages, and their pups were also smaller than normal. These findings in mice suggest that BHPF has the potential to contribute to fertility problems in humans as well.

Zhang and colleagues also tested the leaching of BHPF into hot water filled into 52 commercial drinking bottles made of ‘BPA-free’ plastics. All tested bottles, except three baby milk bottles, were bought in China. The three ‘BPA-free’ polycarbonate baby bottles were obtained from non-Chinese suppliers, because in China all polycarbonate baby milk bottles are currently prohibited. Detectable BHPF levels were found to leach into hot water from 23 out of 52 items tested, including all three tested baby milk bottles (mean concentration 5.6 ng/L), 11 of 18 polycarbonate bottles for adults (mean concentration 19.5 ng/L), 7 of 12 polycarbonate bottles and cups for children (mean concentrations 10.2 ng/L), and both of the two tested Tritan® copolyester products (at 9.5 ng/L (adult product) and 12.9 (children’s product)). A maximum concentration of 81.5 ng/L was found to leach from one polycarbonate bottle intended for adults.

To obtain the first estimates of human exposure, Zhang and colleagues measured BHPF levels in the blood of 100 student volunteers who reported to regularly drink from plastic bottles. BHPF was detected in the blood of 4 of 50 males and 3 of 50 females tested, with a mean level of 0.34 ng/ml and a maximum level of 0.7 ng/ml.

Plastics manufacturers seek to replace BPA due to public pressure and partial bans caused by concerns about its endocrine disrupting properties, making it for example a reproductive toxicant (FPF reported). However, some of the BPA substitutes were shown to produce similar endocrine disrupting effects (FPF reported). The toxicity of BPA substitutes should be carefully characterized in order to avoid multiplying “regrettable substitutions” (FPF reported).

In his articles published in Science 2.0 and American Chemistry Matters, Steven Hentges used the term “fake news” when discussing the Zhang’s  Nature Communications article. Hentges informed that BHPF is not authorized for use in food contact articles in the U.S., and based on this argued that there is “no evidence that [BHPF is] widely used as a replacement for BPA.” However, Zhang and colleagues’ research did not aim to address the situation in the U.S. in the first place. Their study mostly focused on the substance’s effects in the animals, in conjunction with a limited study on BHPF release from food contact articles of which all but three items were bought in China.

Read more

Kendra Pierre-Louis (March 1, 2017). “The ‘safer’ plastics designed to replace BPA may be just as bad for you.Popular Science

Andy Szal (March 3, 2017). “Study: BPA substitute could cause ‘adverse pregnancy outcomes’.ChemInfo

Steven Hentges (March 28, 2017). “BPA-free, here we go again!Science 2.0

Steven Hentges (March 29, 2017). “‘BPA-free’ meets ‘fake news’.American Chemistry Matters


Zhang, Z., et al. (2017). “Fluorene-9-bisphenol is anti-oestrogenic and may cause adverse pregnancy outcomes in mice.Nature Communications 8:14585.