Overcoming difficult, impossible, and meaningless animal testing under REACH: Opportunities for robust chemical risk assessment with non-animal approaches

The European Union (EU) Registration, Evaluation, Authorisation and Restriction of Chemicals Regulation (EC No. 1907/2006) (REACH) includes the principle of testing only when scientifically necessary, integrating mechanisms for data sharing, read-across, and adaptations to minimise vertebrate animal testing. REACH already provides a framework to promote non-animal testing (Annex XI). Nevertheless, the challenge lies in translating its flexibility into consistent practice. New in vivo (vertebrates) studies are still requested to meet information requirements in cases where these tests may add limited or no regulatory or scientific value. In this paper, an initiative of the Animal-Free Safety Assessment (AFSA) Collaboration aimed at defining specific scientific and procedural criteria to identify when animal testing is difficult, impossible, or meaningless (DIM), and how non-animal methods can effectively address such cases. Objective DIM criteria were defined and applied to screen REACH registration dossiers for potential DIM testing cases. More specifically, the AFSA DIM initiative identifies concrete scenarios where animal testing adds no value and demonstrates how existing non-animal approaches can address information needs in those situations. Based on these cases, the following recommendations were: i) further refine the DIM criteria and considerations to be suitable for other REACH endpoints, prioritising human health; ii) evaluate adaptations for avoiding DIM testing for human health endpoints; iii) address more specifically the use of exposure-driven assessment under Next-Generation Risk Assessment (NGRA) considerations (major use of exposure-driven assessment).