Toxicological hazard and risk assessments are ideally conducted using robust and reliable data on the substance in question. We are often faced with a lack of, or only limited, substance-specific data for certain endpoints, referred to as data gaps. In its simplest form, read-across makes use of data on a closely-related surrogate (source substance) to predict the potential (eco)toxicity of the target substance.

Use of read-across is becoming more and more common in REACH registrations, in line with the regulatory drive to reduce vertebrate animal testing. This approach is especially valuable for higher tier and more complex endpoints (e.g. reproductive toxicity) where the alternative approaches – for example in vitro and computational methods – are of only limited use.

The ECHA (2017) Read-Across Assessment Framework (RAAF) is the go-to source to understand how an Agency evaluator will assess the read-across within REACH submissions. The key point is that all cases of read-across need evidence-based support and adequate justification. A read-across hypothesis must be constructed either on the basis that the source and target substances undergo (bio)transformation to a common product(s), or on consideration that different compounds may induce the same type of effect. Critically, justifications should be substance- and endpoint-specific, rather than of a generic nature.

How best to go about justifying the intended read-across? In our experience, the ideal way to achieve this is by attaching a separate read-across justification report to section 13 in IUCLID, complete with appropriate (evidence-based) scientific support for all arguments made. It is important to include a data matrix summarising all the available study results (phys-chem, environmental fate/behaviour, and (eco)toxicity) of the source and target substances, along with a thorough comparison (including differences) between the datasets. The substance ID (constituents and impurities) and potential bias in the dataset (how/why the key source substance(s) was selected) are other priority areas for discussion.

ECHA (2016) guidance on “How to prepare registration and PPORD dossiers” gives us a heads up on how to go about populating read-across cases in IUCLID. Endpoint Study Records (ESRs) for both the source and target substances are necessary for any endpoint utilising read-across and, according to the RAAF document, should be included for all studies referenced in the data matrix. A reduced level of detail is acceptable for target ESRs and these are subject to a limited completeness check, though these should be cross-referenced to the relevant source record(s) and include the read-across target substance as the test material. Registrants should ensure that they have appropriate access to use study data on the surrogate(s) as part of their registration dossier and are required to indicate their relation with the provided information in the data access field in IUCLID.

At bibra, we have extensive experience in identifying potential read-across surrogates and constructing read-across justifications, both in the EU and further afield. If you would like to discuss how we can help, please get in touch.

 

 

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