Read-across approach

One of the key intentions of the EU’s REACH regulation is to minimise the number of new tests carried out on vertebrates, whilst still ensuring the safe use of substances and mixtures. One significant way of doing this is to assess the (eco)toxicology of a “target” compound using the data from one or more “source” compounds, chemical substances that are structurally similar, with similar physico-chemical characteristics, and that would be expected to have a similar (eco)toxicity profile. Using data on closely-related surrogates to fill data gaps on the target substance is known as a “read-across” approach.

In principle, read-across data on source compounds can be used to predict certain physicochemical properties, mammalian toxicity, environmental fate and ecotoxicity of the target substance. Indeed, such information can be used to fulfil the regulatory obligations of the registrant (e.g. Standard Information Requirements under REACH) without resorting to a potentially costly and animal‑intensive trip to the testing laboratory. For any of these endpoints, read-across may be considered in a qualitative or quantitative manner. It is critical that the use of read-across is substantiated for each endpoint for which it is employed. Even if the overall justification seems acceptable, it is possible that read-across for a particular endpoint could be considered inappropriate and consequently rejected by a regulator.

Read-across must, in all cases, be justified scientifically and documented thoroughly. The supporting documentation (including a data matrix) is essential in allowing independent assessment of the adequacy of the read-across approach undertaken, and can easily fall short of the regulator’s expectations. We can also embellish a data matrix with QSAR predictions and/or Klimisch reliability scoring of the available data.

Aspects of the read-across approach play a central part in many of the toxicological assessments we carry out. Having identified gaps in a (eco)toxicological data set, we identify potential candidates for application of the read-across approach. We are often aided by computational tools, such as ChemIDplus and the OECD QSAR Toolbox, but we always apply our own expert judgement of the suitability of a surrogate (considering the structure, molecular weight/size and physical properties, for example). Our team of experienced toxicologists routinely uses the read-across approach in hazard and risk assessments across multiple sectors, including:

We also have extensive experience constructing read-across justifications for regulatory submissions in the EU (e.g. REACH) and further afield (including in the US and China), and maintain our awareness of the most recent guidance documents from international (OECD) and European (ECHA) authorities on the use of the read-across approach, including ECHA’s 2017 “read-across assessment framework (RAAF)”.

 

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