A first focus on the phase I biotransformation pathways followed by a selected set of bisphenol A alternatives
Year: 2026
Type: conference-paper
Abstract: Bisphenol A (BPA) is widely used in the production of polycarbonate plastics and epoxy resins, to manufacture numerous consumer products including food and beverage containers, lacquers and coatings. BPA is a well-studied endocrine disruptor with potential adverse effects on human health, including reproductive and metabolic disorders. Conversely, for many BPA alternatives, there remain major data gaps of knowledge, notably as regards their metabolic fate and potential bioactivation pathways.In this study, we present novel data obtained using in vitro human hepatic models for a first set of BPA alternatives prioritized within PARC. Following full mass-balance studies in HepaRG cells and radio-HPLC metabolic profiling, we started to explore the specific cytochromes P450 isoforms involved in the phase I biotransformation of BPAP, BPE, BPZ, TBBPA, TCBPA, by screening these activities using human CYP-recombinant supersomes.Supersomes were exposed for 30 minutes to 12.5pmol of BPAP, BPE, and BPZ, or to 1nmol of halogenated bisphenols, including 2.5 kBq/molecule. All experiments included negative controls. Radioactivity was counted and supernatants were individually analysed by radio-HPLC to assess the CYP450-dependant formation of metabolites. Current results demonstrate notable differences in the metabolic fate of the different BPA alternatives assayed, both quantitatively (global metabolization rate) and qualitatively. Despite the predominance of phase II conjugation pathways, phase I oxidative pathways were evidenced for several substances, and differences in the XMEs involved were also highlighted. Next steps will consist in completing the assays for additional substances and characterize associated enzymatic constants. These findings provide critical data to achieve a better characterization of the hazards, and to progress towards a better risk assessment of BPA substitutes. By elucidating their metabolic fate, these researches also contribute to regulatory assessments.
Source: HAL
Institutions: Toxicologie Alimentaire, MetaboHUB
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7205305201