Ask a RIFM Scientist

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How does an endpoint-specific framework for read-across analog selection impact RIFM’s Safety Assessment Program?

Holger Moustakas, PhD

As a crucial part of its commitment to animal-alternative testing, the Research Institute for Fragrance Materials (RIFM) employs clustering, organizing chemicals into structurally similar groups, and read-across, using data from one substance to help understand a similar substance. Based on the collective experience developing and evaluating more than 1,500 read-across materials, RIFM scientists’ understanding of clustering and read-across has significantly improved over time. (RIFM’s peer-reviewed paper, “Clustering a Chemical Inventory for Safety Assessment of Fragrance Ingredients: Identifying Read-Across Analogs to Address Data Gaps,” is available for free download.)

The Expert Panel for Fragrance Safety, an independent, international team of researchers and academics with no ties to the fragrance industry, provides RIFM scientists with guidance. Working with Expert Panel chemists, RIFM’s computational toxicologists tailor read-across options specific to each endpoint rather than simply using a conventional rule set that applies to all endpoints. For example, read-across analog selection for one endpoint may require a strict standard for structural similarity. In contrast, selection for another endpoint may be based on other properties that we, as experts, know are important toxicological factors for that area of human health or environmental effects. For example, the respiratory toxicity endpoint has less data available, so read-across options must be stricter in structural similarity. Therefore, a more conservative rule set is applied compared to that used for the genotoxicity endpoint.

This endpoint specificity in read-across analog selection makes read-across a more scientific process. In addition, it expands the potential read-across options RIFM scientists have, which allows them to ensure the safety of more fragrance ingredients while avoiding extra testing and saving animal lives. RIFM scientists submitted a paper on the topic for peer-reviewed publication in mid-September. Once published, this paper – as with all of RIFM’s published science – can be downloaded free at the open-access Fragrance Material Resource Center.

Senior Scientist Holger Moustakas, PhD, leads RIFM’s computational chemistry efforts, including read-across solutions.

Read more: What is read-across, and how does it save animal lives?