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 the 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 assess 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 the 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.