Adverse outcomes of the newly emerging bisphenol A substitutes

BPA and its analogues are facing increasingly stringent regulations restricting their use due to the increasing knowledge of their harmful effects. It is therefore expected that novel BPA analogues and alternatives will replace them in plastic products, cans and thermal paper to circumvent restrictions imposed by legislation. This raises concerns about the safety of "BPA-free" products, as they contain BPA substitutes whose safety has not been sufficiently assessed prior to their market introduction. The regulatory agencies have recognised BPAP, BPBP, BPC2, BPE, BPFL, BPG, BPP, BPPH, BPS-MAE, BPS-MPE, BP-TMC, BPZ and the alternatives BTUM, D-90, UU and PF201 as compound with insufficient data regarding their safety. We demonstrate that the mentioned compounds are present in consumer products, food and the environment, thus exhibiting toxicological risk not only to humans, but also to other species where their toxic effects have already been described. Results of in silico, in vitro and in vivo studies examining the endocrine disruption and other effects of BPA analogues show that they disrupt the endocrine system by targeting various nuclear receptors, impairing reproductive function and causing toxic effects such as hepatotoxicity, altered behaviour and impaired reproductive function. In vitro and in vivo data on BPA alternatives are literally non-existent, although these compounds are already present in commonly used thermal papers. However, in silico studies predicted that they might cause adverse effects as well. The aim of this article is to comprehensively collate the information on selected BPA substitutes to illustrate their potential toxicity and identify safety gaps.