Read Across Approach Toxicology

Our work

The use of toxicity data on a structurally-similar compound to evaluate a substance that has been inadequately tested – the so-called “read-across” approach – is a crucial part of the toxicologist’s skill set. Exploiting read-across can minimise the number of new tests conducted on vertebrate animals, while still ensuring that chemicals are safe for workers and the general population. We have been routinely using read-across in our hazard and risk assessments for many years, and have often incorporated it into the REACH regulatory submissions we have prepared.

Read-Across and REACH

Read-across is one of the key options described in the EU REACH regulation for deviating from the standard information requirements. ECHA have published guidance on using read-across in REACH dossiers, which sets out the standards that have to be met. We have extensive experience of drafting read-across justification reports to these requirements, including preparing a data matrix, and advising on potential in silico or in vitro testing that could be used to support a read-across strategy.

Click to see our work in the REACH industry

Approaches

There are two general approaches to read-across. In the first, data from a small number of “analogues” are used to fill data gaps in the target compound (by extrapolation). The other approach is the “category” approach, where a trend is predicted in a structurally-related group of substances. In this approach, data gaps are filled by interpolation.

Scenarios

ECHA guidance on read-across establishes a number of scenarios. In general, these can be divided into those where compounds are predicted to be transformed or broken down (e.g. by metabolism) to common compounds, and those where compounds are predicted to interact with the same biological target. We have a wide range of experience drafting read-across justifications for both of these scenarios.

Some of our case studies in this area

Determining a suitable read-across surrogate for a pharmaceutical impurity

Case study

Following analytical studies on an intravenous drug product, an organic leachable from the container closure system (CCS) was detected, identified and quantified.