Substitution of bisphenol A: a review of the carcinogenicity, reproductive toxicity, and endocrine disruption potential of alternative substances

Abstract

The use of bisphenol A (BPA) is restricted due to its reproductive toxicity and endocrine disrupting (ED) properties. The public concern and regulatory restrictions on BPA stimulated the development of alternative substances to replace BPA. The aim of this study is to review the available data on carcinogenic, mutagenic, reproductive toxicity, and ED properties of BPA alternatives used in consumer products. The focus is on the potential hazard for (young) children and/or pregnant women. An inventory of known potential alternative substances (n = 99) was made, of which 20 were prioritized based on reported use by the general population. For all the selected alternatives, data on ED potential, carcinogenicity and reproductive toxicity was very limited or even absent (i.e. Tefacid Stearic 95, Bisphenol C, AP, and P). For the alternative substances bisphenol S (BPS), bisphenol AF (BPAF), p-tert-butylphenol and to a lesser extent bisphenol F (BPF), fluorine-9-bisphenol (BHPF), bisphenol E, M, and Z (BPE, BPM, BPZ), Irganox 1076, and butylated hydroxytoluene (BHT), the data indicates a reproductive toxicity hazard with a possible ED mode of action. 3,3′,5,5′-Tetrabromobisphenol A (TBBPA) tested positive for carcinogenicity. Data gaps are present for most of these substances. In this study, data on reproductive toxicity and/or ED potential were only negative, although not complete, for benzoic acid and Irganox 1010, tetra methyl bis phenol F (TMBPF) and bisphenol-A bis(diphenyl phosphate) (BDP). A full evaluation of all data, including in vitro data, is recommended to guide targeted testing prioritization.

Keywords:

• Bisphenol A
• bisphenol A alternatives
• endocrine disruption
• sensitive populations
• reproductive toxicity
• children
• pregnant woman
• hazard assessment

Acknowledgements

The authors thank Aldert Piersma, Bianca van de Ven, Gerlienke Schuur, Julia Verhoeven, Betty Hakkert, and Fleur van Broekhuizen for their scientific support in developing the selection method of alternative substances and materials, and for the helpful discussions on the regulatory requirements on hazard information.

Declaration of interest

This research was financed by the Dutch Ministry of Health, Welfare and Sports (VWS) (project 5.1.12: endocrine disruptive compounds). Prior to submission, the manuscript was delivered to VWS as finalized product. This submission was not intended to, and did not, result in any changes to the manuscript. The authors confirm that the present review and conclusions drawn reflect the professional work product of the authors, and that there are no conflicts of interest related to any legal or regulatory proceedings related to this review’s content.

Supplemental material

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