Non-animal alternatives and read-across to fulfil regulatory data requirements

Regulatory frameworks increasingly require extensive hazard and risk information for chemicals. At the same time, there is increasing pressure to minimise animal testing due to ethical, legal and cost considerations.

This has created a strong need for reliable non‑animal alternatives that can meet regulatory data requirements without generating new animal studies. Among these approaches, read‑across is widely used but remains challenging: it demands a clear scientific rationale, robust evidence, and detailed documentation to satisfy regulators. For many companies, these expectations can be difficult to meet, making the use of non‑testing alternatives both essential and inherently complex.

What are non-testing alternatives and read-across?

Non-animal approaches allow companies to meet information requirements without generating new animal data. These approaches include the use of existing data from similar compounds (i.e. read-across), in-vitro and in-silico methods (i.e. computational models such as Quantitative Structure-Activity Relationship - QSAR) and weight‑of‑evidence assessments.

Among these alternatives, read-across is one of the most widely applied approaches. The process involves predicting the properties of a ‘target’ substance by using data from a structurally or mechanistically similar ‘source’ substance. The use of read-across data when similarity is demonstrable and the scientific rationale is clear, can substantially reduce the need for new testing, minimizing costs, but providing evidence to support compliance with a range of international regulatory frameworks, including but not limited to:

• EU legislation: REACH, CLP, Biocidal Products Regulation, Cosmetics Regulation, 
• OECD test guideline and assessment frameworks: OECD QSAR Toolbox
• US EPA programs: TSCA
• And other international and national chemical management schemes.

Read-across data must be supported by a transparent hypothesis, consideration of uncertainties, including impurities and metabolic differences, and adequate supporting evidence. Although requirements vary by jurisdiction, widely recognised frameworks – such as the EU REACH Annex XI (1.5) provisions and ECHA’s Read-Across Assessment Framework (RAAF) – provide robust examples of how read-across justifications can be structured and evaluated and are often used as a reference or benchmark globally.

When appropriately substantiated, read-across can be used for hazard identification, hazard characterization, and risk assessment, contributing to regulatory decision-making while supporting the principles of animal welfare, proportionality, and efficient data generation.

Challenges and considerations – Particularly for small and medium enterprises (SME)

Larger companies often have internal expertise in toxicology, chemistry and regulatory science, whereas SMEs may struggle to meet the evidential expectations set by regulatory authorities. Key challenges include:

• Limited in-house resources to collect, analyse and interpret scientific data.
• Difficulty understanding structural similarity requirements and metabolic considerations.
• High expectations for transparency and documentation in RAAF-aligned justifications.
• Costs associated with obtaining source substance data from co-registrants or consortia.
• The need for uncertainty assessment and supporting evidence outside the core analogue data.

For SMEs, expert support often makes the difference between successful acceptance of read-across and a costly request for additional testing.

Experienced support for your business

Ricardo’s chemical experts offer comprehensive technical and regulatory expertise to help companies — especially SMEs — navigate the complexities of read-across and optimise their use of non-testing alternatives under REACH.

Support includes:

• Identification of suitable analogues: structural and toxicological screening to select the most defensible source substances.
• Development of robust read-across hypotheses: including mechanistic reasoning, metabolic assessment and impurity comparison.
• Construction of data matrices and similarity justifications: prepared in line with expectations of regulators.
• Design and execution of Weight-of-Evidence approaches to reinforce analogies, ensuring that the read‑across justification is scientifically robust and capable of withstanding regulatory scrutiny.
• Documentation and dossier preparation for regulatory submissions, providing the level of transparency and structure required for authorities to accept non‑testing approaches.
• Cost-effective strategy development prioritising endpoints where read-across is most applicable.
• Stakeholder engagement support including communication with co-registrants and/or data holders.

Through this integrated approach, Ricardo enables clients to reduce or eliminate the need for animal testing, avoid unnecessary costs, accelerate dossier preparation and achieve regulatory compliance with high confidence.

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Advancing environmental chemistry and toxicology for a safer, sustainable future The Environmental Chemistry and Toxicology team at Ricardo is at the forefront of understanding how chemicals interact with humans and the environment and assessing their toxic effects on organisms and ecosystems using traditional and innovative approaches. By combining our knowledge of environmental chemistry, fate, and (eco)toxicology, our highly motivated team investigates the intricate composition and behaviour of substances in the environment. To this end, we deliver insights that drive impactful solutions and develop strategies to mitigate risks. Learn more