Read-across

Read-across is a powerful tool which can be used as adaptation of information requirements following REACH Annex XI, Section 1.5. It reduces the number of animal tests to be performed and thereby the costs for registrants to fulfil the information requirements under REACH. Therefore, it has become one of the most commonly used alternative approaches for data gap filling in registrations submitted under the REACH Regulation. It involves the use of relevant information from analogous substance(s) (source substance(s)) to predict properties for the substance(s) under consideration (target substance(s)).

At Triskelion we noticed that during the last years, read-across approaches are under higher scrutiny by ECHA. Rejection of the read-across approach during a Compliance Check by ECHA can have a high impact, as it will result in the request of dedicated testing with the target substance. Ultimately, the dossier will be more costly and time-consuming. To minimize the risks, the read-across approach in your registration dossier should follow the first-time right principle and provide a solid justification in accordance with the Read Across Assessment Framework (RAAF) as laid down by ECHA in 2017. Already existing read-across justifications may need updating to comply with the current requirements.

In accordance with the RAAF, the read-across justification must address the chemical structure similarity, physical-chemical properties, environmental fate behaviour, the target endpoints, etc., of both target and source substance(s), in order to justify the appropriate read-across hypothesis. The RAAF document contains several scenarios to identify the correct read-across hypothesis, for both analogue approaches (one source and one target substance) as well as category or grouping approaches (a group of similar substances which could all serve as source or target substance, depending on the property). To further strengthen the RAX justification, supporting information to elucidate mechanistic toxicological pathways could be included as well as dedicated toxicokinetics data. In addition, available in vitro, in chemico and in silico studies may be included to increase the robustness of the hypothesis. If available, this information can be added to create a tailor-made RAX justification. All aspects of the read-across justification should be documented transparently and the approach should be unbiased. Again, the RAAF document can be followed using the pre-defined set of assessment elements (AEs) to address critical scientific aspects.

It should also be noted that on the other hand, ECHA uses the read-across approaches in registration dossiers as basis for the grouping the chemical universe, which in its turn is used in the group assessment approach for identification of regulatory action. Read-across in your registration dossier can therefore pose risks for your registration, as regulatory actions such as restriction of additional hazard classification for the source substance, can also be required for your substance. Therefore, the risks and benefits of applying a read-across approach should be analysed before using this adaptation of information requirement in your REACH registration dossier. This could also be done retrospectively, by evaluating the read-across currently applied in your REACH registration dossier followed by possible strategic actions.

Take-away

• It is essential to construct a solid read-across justification in order to pass the compliance check. If rejected, testing with the target substance will be requested.
• Applying read-across to hazardous substances might pose a risk to your registration in terms of regulatory action. Therefore, always assess these risks before applying read-across.