Obesity is not the only concern documented for

Obesity is not the only concern documented for BPA. Epidemiological studies have identified neurocognitive effects of BPA and newly incident coronary artery disease, and laboratory studies strongly suggest BPA is an ovarian toxicant. The rapidly rising evidence of adverse effects has prompted manufacturers to substitute BPA with various bisphenols (BPS, BPP, BPZ, and BPF, to name a few). These chemicals were not required to be proven as safer alternatives because of the Toxic Substances Control Act, which, until June, 2016, when President Obama signed legislation updating the law, presumed chemicals to be innocent until proven guilty in terms of toxicity in the USA, requiring little toxicity testing data before approval for widespread use by the Environmental Protection Agency. What little we know about one BPA replacement, BPS, suggests serious concerns. BPS has been found to be as oestrogenic in laboratory studies and as toxic to embryos as BPA, and even more persistent in the environment. Is it glutathione s-transferase obesogenic in humans? In , Buyun Liu and colleagues examine data from the 2013–14 National Health and Nutrition Examination Survey to study cross-sectional associations of urinary concentrations of BPA, BPF, and BPS with obesity in adults. Their analysis confirms persistent associations of BPA with obesity, despite lower exposures than previously studied. Although associations of urinary BPF or BPS with body-mass index or obesity were not significant, Liu and colleagues\' analyses raise more questions than answers about whether non-A bisphenols are obesogenic. The authors used statistical models to examine effects of each bisphenol independent of the other; however, no potency data are available to aggregate effects of model relationships in aggregate across the bisphenols, and examination of interactions to evaluate synergy or antagonism were not done. Exposures to BPF and BPS were much lower and less prevalent than BPA and the cross-sectional evaluation of adult obesity is an important limitation of the study design given the known life-course origins, especially early life exposures that can have a big impact on adult obesity. Longitudinal studies are needed, especially to examine pregnancy and early childhood exposures, as are studies that assess the period after the introduction of BPA. Most longitudinal cohort studies of BPA exposure are limited by missing measurements of non-A bisphenols and missing associations could be caused by imprecision in the measurement of bisphenol exposure. Although these issues complicate interpretation of human studies, they exemplify the problem of so-called regrettable substitution. The economic benefits of substituting BPA in the linings of aluminium cans with an alternative free of health effects (US$1·74 billion per year) were found to nearly outweigh the costs of a natural alternative oleoresin ($2·2 billion per year), and this analysis was limited to benefits associated with reductions in BPA-attributable childhood obesity and coronary artery disease. Oleoresin is not necessarily a feasible alternative for all canned foods, but substitution of BPA with BPF, BPS, or another bisphenol might result in the same associations with adverse health outcomes as BPA, after years of studies in the laboratory and human beings. The European Commission has the opportunity to set the platform for a stronger regulatory framework for bisphenols and other endocrine disrupting chemicals (EDCs) that necessitate the use of safer alternatives when laboratory and other studies suggest that they cause adverse effects. The stakes are high; EDC-associated diseases and disabilities extend well beyond bisphenols to a broader array of synthetic chemicals, with effects including adverse neurodevelopmental outcomes, diabetes, cardiovascular disease, and male and female reproductive disorders. The costs of EDC exposures are estimated to be €163 billion in the European Union and $340 billion in the USA. Although these estimates are based on known exposures, they suggest the large, potential societal benefits of proactive and thorough screening of new chemicals before they can be introduced into the market, and reconsidering the use of non-A bisphenols and other potentially regrettable substitutes.