ECHA Board of Appeal rules that a positive in vitro result alone does not trigger in vivo genotoxicity testing

The European Chemicals Agency (ECHA) Board of Appeal has annulled two compliance check decisions requiring in vivo mutagenicity testing following positive results in bacterial gene mutation (Ames) tests.

ECHA had interpreted the Column 2 provisions under Section 8.4 of Annexes VII, VIII, and IX of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation as meaning that a positive result in an in vitro test automatically gives rise to a concern requiring in vivo follow-up testing. However, the relevant provisions refer to a positive in vitro result “which gives rise to concern.” The Board of Appeal found that this wording establishes two distinct conditions: there must be a positive result, and that result must give rise to a concern that the registered substance may have mutagenic properties.

In both cases (A-004-2025 and A-005-2025), the Appellants provided information explaining why the positive Ames test results did not indicate a concern, including that the results reflected the properties of metabolites rather than those of the registered substances. The Board of Appeal annulled the Contested Decisions because ECHA had not sufficiently addressed these arguments.

The precedent-setting decisions clarify that available evidence and explanations must be considered when interpreting positive in vitro genotoxicity results. Importantly, the Board of Appeal recognised that vertebrate animal welfare and the principle of proportionality must be considered when interpreting and applying REACH information requirements.

The rulings represent an important step away from automatically triggering animal tests based on individual in vitro assay results and towards a scientifically robust evaluation of all available evidence, supporting human safety.

Read the Board of Appeal decisions in cases A-004-2025 and A-005-2025.