Endpoints Lacking Animal-Free Alternatives Under REACH and the Remaining Challenges

The European Union’s REACH regulation mandates comprehensive chemical testing to ensure human and environmental safety, prioritizing non-animal methods whenever possible. Despite significant advancements in alternative testing strategies, certain endpoints still require animal studies due to the lack of validated in vitro, ex vivo or in silico models. This paper examines these gaps by tonnage band, highlighting key areas where non-animal alternatives remain insufficient. Acute oral, dermal, and inhalation toxicity tests, repeated-dose toxicity studies as well as reproductive and developmental toxicity studies are among the endpoints that are still reliant on animal testing. While progress has been made in developing alternatives such as Defined Approaches (DAs) that may integrate physiologically based kinetic (PBK) modeling, these methods are not yet fully validated for regulatory acceptance. Continued investment in research, validation and international collaboration is essential to accelerate the validation and implementation of animal-free alternatives.