What Does "success" Look Like in Compliance Check Decisions by the European Chemicals Agency? the Curious Cases of Accepted Read-Across Adaptations.

Under the European Union’s REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) regulation, the European Chemicals Agency (ECHA) is required to assess the compliance of safety data submitted by chemical registrants. ECHA must check a proportion of registration dos­siers for compliance. From 2010 to 2023, 4,854 compliance checks (CCHs) were conducted. When dossiers lack required studies or use inappropriate adaptations, ECHA issues decisions that are publicly available. As of April 2, 2024, 2,311 such decisions had been published. This study sys­tematically analyzed these published CCH decisions, focusing on ECHA’s findings of non-compliant REACH registrations and the use of adaptations to standard information requirements. We found that over 70% of published CCH decisions included at least one adaptation, with “read-across” being the most common (48%). Among these, 83 documents contained read-across adaptations with jus­tifications that ECHA deemed plausible. To understand what made these read-across hypotheses acceptable, we evaluated them using 17 assessment elements that capture specific arguments regis­trants proposed to justify the adaptation. Elements of “acceptable” read-across hypotheses included strong evidence of (i) toxicokinetic similarity between the registered substance and its analogues, and (ii) toxicodynamic similarity, supported by bridging studies. Additional support from in vitro studies and QSAR predictions further strengthened the accepted read-across hypotheses. Overall, this analysis provides insights into what constitutes a successful read-across under REACH data requirements. By identifying and evaluating accepted cases or read-across adaptations, we high­light best practices for establishing scientifically robust justifications for chemical similarity that can meet ECHA’s high regulatory standards.