In June 2026, the European Chemicals Agency (ECHA) submitted its sixth report under Article 117(3) of the REACH Regulation, systematically reviewing the current status of alternative methods to animal testing in chemical registrations between 2008 and July 2025. The report indicates that in vitro methods have achieved absolute dominance for endpoints such as skin corrosion/irritation and serious eye damage/eye irritation; however, for complex endpoints such as repeated dose toxicity and carcinogenicity, completely eliminating animal testing still faces significant scientific and regulatory challenges. CIRS provides the following interpretation of this report.
Key Findings
1. Adaptations remain the mainstream approach
- Overall, the proportion of registrants using adaptation methods (Adaptations, such as read-across, QSAR, weight of evidence, data waiving, etc.) (approximately 36.7%) remains higher than experimental studies (31.9%).
- Read-across is the most commonly used adaptation method (24.4%), followed by data waiving (6.4%), weight of evidence (3.2%), and QSAR (2.7%).
2. Significant reliance on legacy data
- Approximately half of the experimental studies in the database were completed before REACH entered into force (prior to 2009), indicating that current assessments heavily rely on historical legacy data.
- The proportion of legacy data is particularly high for lower-tier endpoints such as acute toxicity, skin irritation/corrosion, and eye irritation.
3. Notable growth in in vitro methods
- In vitro methods have become mainstream for three endpoints: skin corrosion/irritation, serious eye damage/eye irritation, and skin sensitization.
- Between 2022 and 2025, the vast majority of new studies for these three endpoints employed in vitro methods (for example, in vitro studies for skin irritation/corrosion accounted for 89.4%).
- However, some in vivo studies are still being submitted for the skin sensitization endpoint, primarily because the physicochemical properties of substances are unsuitable for in vitro testing, or because in vitro results are inconclusive.
4. Significant decline in new substance registrations
- Between 2022 and 2025, only 424 new substances requiring hazard information completed registration, representing a decrease of approximately 50% compared to the previous reporting period (889 substances in 2019–2022).
- Among these, 74% belong to the lowest tonnage band (Annex VII, 1–10 tonnes/year), resulting in relatively low overall data requirements.
5. Significant endpoint variations
- Lower-tier endpoints (acute toxicity, algal toxicity, etc.): Experimental studies account for a relatively high proportion.
- Higher-tier endpoints (repeated dose toxicity, reproductive toxicity, carcinogenicity, etc.): Greater reliance on adaptation methods, particularly read-across. However, for some endpoints, the quality of adaptation justifications was insufficient, leading to requests for supplementary experimental data following compliance checks.
Future Outlook
The European Commission is developing a roadmap for the gradual phase-out of animal testing, aiming to fully adopt non-animal methods in chemical safety assessment. ECHA is establishing the Collaborative Platform for Alternative Approaches to Testing (CP-AAT) to coordinate Member States, EU institutions, and stakeholders in identifying regulatory needs, harmonizing understanding, and advancing the validation and standardization of alternative methods.
Furthermore, ECHA launched a six-year research framework contract in 2023 with a budget of €4.2 million, focusing on supporting in vitro toxicokinetics, the application of omics data, and the development of integrated testing strategies. Combined with the upcoming EU Chemicals Public Data Platform, ECHA aims to build regulatory confidence in the new generation of non-animal methods based on high-quality, interoperable data.
ChemRadar Insights
Although scientific innovation and digital tools are rapidly expanding the "toolbox" for non-animal assessment, the following challenges must be addressed to achieve full replacement:
- Difficulties in replacing complex endpoints: For complex endpoints such as repeated dose toxicity, carcinogenicity, and chronic toxicity, it remains difficult to completely replace in vivo studies with a single non-animal method while maintaining high levels of protection for human health and the environment.
- Quality of adaptation justifications: The quality of adaptation justifications (particularly read-across) submitted by registrants varies considerably and often fails to meet legal requirements, resulting in subsequent requests for animal testing.
- Scientific validation and regulatory confidence: More cross-substance validation, coordinated data generation, and unified assessment standards are needed to establish sufficient regulatory confidence in New Approach Methodologies (NAMs).
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