A recent manuscript, "Learning from experience: A retrospective analysis of read – across strategies for surfactants under REACH  –  An overview" by Schmitt et al. (2025), provides a critical review of why many read-across submissions under REACH fail to gain acceptance by authorities. The authors reviewed 72 ECHA Final Decisions covering 24 major surfactant groups submitted between 2010 and 2013, aiming to improve future read-across practices and reduce unnecessary animal testing. 

Despite the prevalence of read-across as a strategy for REACH compliance, only 6 of the 72 cases reviewed were accepted without condition – three others were accepted with the requirement for further data. The study offers valuable insight into recurring issues that led to rejection, helping to inform more robust read-across justifications in the future. 

Common Reasons for Read-Across Rejection 

The most frequent reasons for rejection included: 

• Inadequate bridging studies.

• Missing or insufficient toxicokinetics (TK) and toxicodynamics (TD) data.

• Incomplete physicochemical characterisation.

• Poor or outdated source study quality.

• Unclear or unsupported structural similarity. 

These shortcomings often resulted in failures to demonstrate robust scientific justification as required under ECHA’s Read-Across Assessment Framework (RAAF, 2012). 

Substance Characterisation & Structural Similarity 

Many read-across justifications failed due to insufficient substance identification. In particular, ECHA cited issues such as: 

• Lack of detail on alkyl chain length distributions.

• Degree of ethoxylation or branching not being quantified. 

• Impurity and purity profiles not well characterised.

Themes similar to or, identical, are especially problematic for complex substances and UVCBs. Since structural similarity is a cornerstone of read-across justification, high-resolution substance characterisation is essential. Blue Frog has developed a structured workflow for analysing substance identity and supporting similarity arguments, including clear data-gap assessments and recommendations for further analysis. 

Physicochemical Properties - More Than Just Support Data

Physicochemical parameters are often underestimated in read-across planning but were a recurring reason for ECHA rejections. In the reviewed submissions, missing or poorly justified data (e.g., mean values for log Kow) often weakened the argument. 

Essential properties include: 

• Molecular weight.

• Water solubility.

• Log Kow.

• Vapour pressure.

• Viscosity and pH.

• Critical micelle concentration (CMC)  –  especially important for surfactants.

For surfactants, CMC plays a major role in determining bioavailability and impacts how test results are interpreted. These factors need to be explicitly addressed in the justification. 

Toxicokinetics &Toxicodynamics (TK/TD)

The absence of convincing TK/TD data significantly contributed to rejection decisions. ECHA tends to accept read-across only if: 

• The parent compound is “toxicologically silent”.

• The transformation to the active metabolite is “immediate and/or complete”. 

However, definitions of "immediate" and "complete" are vague, and this area remains scientifically and regulatorily uncertain. One emerging solution involves the use of internal Threshold of Toxicological Concern (iTTC) approaches alongside PBK modelling to establish exposure relevance and enhance cross – route extrapolations. 

Blue Frog has developed a systematic approach to mapping TK/TD profiles and addressing uncertainties directly within the read-across narrative. 

Bridging Studies - Strengthening the Scientific Link 

Bridging studies form a crucial part of the scientific rationale connecting source and target substances. Schmitt et al. highlight that the absence of these studies – or reliance solely on in silico data – led to regulatory rejection. 

Acceptable bridging data might include: 

• In vitro studies (e.g., genotoxicity, cell models).

• In vivo studies where ethically justified.

• Mechanistic or omics-based approaches. 

• QSARs as supporting evidence (not primary justification). 

For example, in the case of varying alkyl chain lengths, bridging studies can demonstrate continuity in biological activity. At Blue Frog, we align study choice with predicted or known mechanisms of action, ensuring the bridging evidence is both targeted and relevant. 

Read-Across Using NAMs 

The use of New Approach Methodologies (NAMs) such as omics, in vitro systems, and computational models is increasingly accepted by ECHA – especially when traditional test data is lacking. However, these tools must be supported by a strong scientific rationale and regulatory engagement. 

Surfactants, with their complex behaviour and properties, present challenges for in vitro interpretation, making NAMs an attractive – but nuanced – option. Blue Frog remains at the forefront of applying NAMs in regulatory submissions and participates in broader EU discussions on their use. 

Data Quality and Study Reliability 

Even when other aspects of the justification were acceptable, poor – quality source data often led to rejection. Common issues flagged by ECHA included: 

• Absence of the fifth tester strain in Ames tests.

• No analytical monitoring in aquatic toxicity studies.

• Use of studies that pre-date current OECD guidelines.

At Blue Frog, we advocate for holding source studies to the same standards as new experimental work. When older studies are used, they must be justified through a weight-of-evidence narrative or supplemented with new data. 

Building Better Read-Across Strategies 

The Schmitt et al. analysis reinforces that read-across remains a viable, valuable approach under REACH – but only when done rigorously. A successful read-across submission must: 

• Demonstrate strong substance identity and similarity.

• Include high – quality physicochemical and TK/TD data.

• Use appropriate bridging studies and/or NAMs.

• Be built on reliable source data and transparent justifications.

At Blue Frog Scientific, we specialise in building read-across dossiers that stand up to regulatory scrutiny. Our team combines regulatory insight, scientific depth, and practical experience to deliver submissions that align with ECHA expectations. 

If you're navigating complex substances, planning a read-across strategy, or need support responding to a compliance check, contact our team of regulatory compliance experts to find out how we can help.