Bisphenol A--Why an adverse outcome pathway framework needs to be applied.
Bisphenol A (BPA) is one of the most widely used and extensively studied chemicals. Numerous studies have reported in vitro effects or animal adverse findings at BPA doses lower than the no observed adverse effect levels (NOAELs) established in regulatory toxicity studies and used for human health risk assessment. Intensive discussions on the adequacy and relevance of test systems have not satisfactorily resolved whether positive or negative animal and/or in vitro findings are more relevant for human health risk assessment purposes. BPA imperfectly mimics endogenous estrogens at membrane-bound estrogen receptors in the fM-nM concentration range, and may have downstream pleiotropic effects such as human seminoma proliferation and mammary gland hyperplasia after in utero exposure which are not detectable in regulatory toxicology studies. We argue that a structured approach like the OECD Adverse Outcome Pathway (AOP) framework is needed to help researchers in designing relevant studies, and risk assessors in evaluating them. The huge amount of experimental data generated for BPA has highlighted data gaps in basic biology and the shortcomings of current approaches to hazard characterization and risk assessment. Establishing AOPs for BPA, and other endocrine active chemicals, will require major scientific as well as training investments by all responsible stakeholders.
Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: rex.fitzgerald@unibas.ch.
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RE
FitzGerald
Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland.
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MF
Wilks
D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D006801:Humans; D019055:No-Observed-Adverse-Effect Level; D010636:Phenols / Q000633:toxicity*; D011960:Receptors, Estrogen / Q000187:drug effects; D018570:Risk Assessment; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds
Adverse outcome pathway; Bisphenol A; Human health risk assessment; Membrane-bound estrogen receptor