Investigation of the potential of bisphenol A substitutes to induce allergic contact sensitization using OECD defined approaches

Bisphenol A is a high production volume chemical used extensively in the manufacture of polycarbonate plastics, epoxy resins, and thermal printer paper with a high potential for occupational and post-production dermal exposure. Bisphenol A-containing plastics were commonly used in food packaging resulting in significant public exposure through leaching into foodstuff. The public is also at risk of dermal exposure due to environmental contamination. Due to public health concerns regarding the potential for endocrine disrupting effects, efforts have been applied to replace bisphenol A with safer alternatives. Bisphenol A has been shown to cause skin sensitization in humans; however, there is a paucity of information available on the sensitizing potential of structural analogues which are increasingly being employed as substitutes. We utilized new approach methodologies (NAMs) addressing key events 1-3 of the adverse outcome pathway for skin sensitization to address the potential of bisphenol A substitutes to induce dermal sensitization. Defined approaches (DA) were applied to further classify and categorize potency according to OECD TG 497. The NAMs and DAs confirmed that bisphenol A was a skin sensitizer in potency category UN GHS 1B. Bisphenol B, AP, and E were also classified as UN GHS 1B sensitizers, and bisphenol AF as UN GHS 1A/1B depending on DA, while 2,4-bisphenol S and F were borderline sensitizers, and bisphenol S was classified as a non-sensitizer. These data provide evidence of skin sensitization hazard for the bisphenol structural analogues tested, except for bisphenol S, suggesting that they present risks for dermal allergy.