Development of Integrated Approaches to Testing and Assessment (IATA) case studies on developmental neurotoxicity (DNT) risk assessment

The EFSA Panel on Plant Protection Products and their Residues (PPR) has developed, as a self-task mandate (EFSA-Q-2019-00100), two adverse outcome pathway (AOP)-informed integrated approach to testing assessment (IATA) case studies answer developmental neurotoxicity (DNT) hazard identification characterisation problem formulation that could support the regulatory decisions for pesticide active substances deltamethrin flufenacet. IATA were developed assess applicability of DNT in vitro battery (IVB), designed explore fundamental neurodevelopmental processes, risk pesticides. For this purpose, an evidence-based-approach methodology was applied: 1) systematic literature review critical appraisal all evidence i.e. human observational studies, vivo data from rodent models new methodologies (NAMs, including high-throughput IVB zebrafish literature) both studies; 2) quantitative uncertainty analysis using expert knowledge elicitation (EKE) probabilistic approach; 3) integration AOP conceptual framework. This stepwise resulted postulation evidence-based network one studies. A quantification weight (WoE) Bayesian allowed postulated AOP. taken conclusions be drawn with acceptable level certainty flufenacet is not neurotoxicant, supporting relevance mechanistic understanding. show DNT-IVB illustrate usefulness AOP-informed decision making. overall activity led improved interpretation by providing plausible link outcomes, which would contextualisation process. Scientific Opinion allows PPR draft several recommendations implementation