Improving consistency in regulatory assessment of repeated-dose toxicity studies: an EFSA checklist-based framework for statistical evaluation.

Abstract

The evaluation of 28- and 90-day repeated-dose toxicity studies in rodents is typically performed at the highest tier of regulatory toxicology. Despite detailed guidance from the European Food Safety Authority (EFSA) and Organisation for Economic Co-operation and Development (OECD), the practical implementation and evaluation of these studies remain challenging and may lead to variability across assessments. In risk assessment of genetically modified organisms (GMOs) intended for import into the European Union, these studies primarily provide information for evidence of adverse effects. A series of structured checklists were developed and internally applied by EFSA to support consistent, transparent, and traceable evaluations of repeated-dose toxicity studies. In this paper, we presented an application to GMO risk assessment as an illustrative example. In particular, this commentary focuses on the checklist for statistical evaluation, developed in 2019 and implemented across the European regulatory framework. This checklist translates EFSA and OECD guidance into operational criteria covering study design, experimental conduct, statistical analysis and reporting, while remaining subject to revision in response to evolving regulatory and scientific developments. We discussed the added value of the EFSA checklist and highlighted its potential to enhance consistency and robustness in regulatory decision-making. Limitations and future perspectives, including the incorporation of quantitative scoring systems and digital implementation, are also discussed.