Assessment of the endocrine disrupting properties of Bisphenol AF according to the EU criteria and ECHA/EFSA guidance.

Endocrine disruptors (EDs) are exogenous compounds that interfere with the hormone system, affecting human health and environment. Specific legislative obligations have been introduced in the European Union (EU) to gradually eliminate EDs in water, industrial chemicals and pesticides. However, identification of EDs is the first and essential step towards regulation and appropriate risk management. Scientific criteria and guidance for ED assessment have recently been established for pesticides in the EU. In this project, the ED properties of the non-pesticide chemical Bisphenol AF (BPAF), analogue and potential substitute of Bisphenol A were evaluated by the application of the EU criteria and guidance in the frame of human health risk assessment. A data dossier was built by a systematic literature review (WOS, Scopus, Pubmed, Embase), title/abstract screening (RAYYAN) and full-text examination. All relevant information was extracted and systematically reported, and reliability and relevance of data were assessed (SciRAP). Data were synthesised into lines of evidence for (i) endocrine activity, (ii) adversity and (iii) general toxicity, and weight of evidence evaluation was applied. The initial analysis of the evidence showed potential endocrine adverse effects and endocrine activity, meeting the ED criteria and leading the assessment to the mode of action (MoA) analysis. The biological plausibility of the link between the adverse effects and the endocrine activity was investigated based on current scientific knowledge. Empirical support for dose-response and temporal concordance was evaluated, and the key events were assessed in terms of essentiality, consistency, analogy and specificity. Finally, an overall conclusion of the ED properties of BPAF was drawn. The EU criteria and guidance for EDs assessment were successfully applied to BPAF demonstrating its endocrine activity and adversity based on weight of evidence methodology and MoA analysis. The Fellow greatly increased her knowledge and hands-on experience on ED assessment in the EU regulatory context contributing to implement transparency and structure in health risk assessment.