How safe is bisphenol A? Fundamentals of toxicity: Metabolism, electron transfer and oxidative stress

SummaryThe FDA recently announced concern about the safety of bisphenol A (BPA) and the need for more research. In the current controversy, scant attention is being paid to toxicity at the fundamental, molecular level, which is the topic of this report. Important information is provided by extensive studies on metabolism. The principal pathway is detoxification, mainly by conjugation leading to a glucuronide. A minor route entails oxidation by hydroxylation to a catechol followed by further transformation to an o-quinone. The catechol-o-quinone couple is capable of redox cycling with generation of reactive oxygen species (ROS) and oxidative stress (OS). o-Quinones are highly electron affinic with very favorable reduction potentials that permit electron transfer (ET) under physiological conditions. Only small amounts are sufficient to generate large quantities of ROS catalytically. There is extensive evidence for production of ROS, which buttresses ET by o-quinone as a plausible source. In addition, there are numerous reports on toxicity to body constituents by BPA. Those adversely affected include the liver, DNA, genes, CNS, reproductive system and kidney. Since a plethora of prior studies links ROS–OS with toxicity, it is reasonable to propose a similar connection for BPA. Cell signaling also plays a role. There are various other factors involved with toxic responses, including age, with the fetus and infants being the most vulnerable. A report concludes that human exposure to BPA is not negligible. The present overview represents a novel, integrated approach to BPA toxicity. A similar article was recently published in this journal which deals with toxicity of prevalent phthalate plasticizers.