Read-Across
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.
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
NAMs for NGRAs
Blog articles
Traditionally, toxicological risk assessment has involved identifying a point of departure (PoD) such as a NOAEL or LOAEL in a study of small creatures, adjusting it to be relevant to humans (to derive, for example, a TI or DNEL), and then calculating the margin of safety to a measured or estimated external exposure. As part of this process, toxicologists have to account for the uncertainties that arise in moving from the species, route and duration of the laboratory animal study to the real human world.
FDA memoranda: genotoxicity and carcinogenicity assessments of ENDS
Blog articles
As discussed in a previous blog post, the U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has issued several “scientific policy memoranda” that provide some great insights into the Agency’s evaluation process. In June 2024, the FDA made two new memos available that relate to the genotoxicity and carcinogenicity assessment of chemical constituents of Electronic Nicotine Delivery Systems (ENDS).
FDA memoranda: shedding light on health risk assessment of ENDS in PMTA submissions
Blog articles
In 2016, the United States (US) Food and Drug Administration (FDA) ruled that Electronic Nicotine Delivery Systems (ENDS) were to be regulated just like more traditional tobacco products, meaning that ENDS (e-cigarettes and e-liquids) are subject to premarket review requirements, despite containing no tobacco. ENDS manufacturers must therefore submit a Premarket Tobacco Product Application (PMTA) to the FDA Center for Tobacco Products (CTP) in order to have any chance of legally marketing their products in the US.
Some industries we work in
REACH
We are a leading supplier of REACH compliance services, assisting chemical manufacturers, importers and downstream users comply with their REACH Regulation responsibilities.
Pharmaceuticals
Our team is adept at preparing critical toxicological reports - we regularly provide assessments of novel or unexpected impurities, excipients and other intentionally-added substances, and extractables and leachables.
Extractables + Leachables
We provide valuable support to the pharmaceutical, medical device and processing equipment industries by producing screening reports and, if warranted, full risk assessment reports relating to extractables and leachables (E&L).
