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The Sustainable Chemistry through Contemporary Toxicology Specialty Section, the In Vitro and Alternative Methods Specialty Section, and the Women in Toxicology Special Interest Group invite you to join us for an enlightening session during the 2022 SOT Annual Meeting on Tuesday, March 29, at 11:00 am (PT) entitled “Cross-Species Extrapolation: Opportunities in a 21st-Century Regulatory Nonanimal Testing World.” The session will feature four invited speakers, including from the US Environmental Protection Agency (US EPA) and the European Food Safety Authority (EFSA), who will share their views on the changing regulatory context in both North America and Europe. The changes pose challenges that provide opportunities for cross-species extrapolation to inform a 21st-century regulatory nonanimal testing agenda for assessing both human and environmental health. The session will be held as a Roundtable to encourage discussion between researchers and regulators regarding use of computational results to inform decision-making.

To drive the discussion, we invite you to provide your opinion on the opportunities and challenges of using cross-species extrapolation and bioinformatics to support regulatory decision-making. Please spend a few minutes to fill out the survey form to have your thoughts discussed. (Please complete by March 1.)

Session Description

Regulatory decisions surrounding chemical safety are based primarily, although not exclusively, on human and environmental protection. Historically, there has been a reliance on animal toxicity testing to inform hazard and risk assessment. Typically, mammalian data drive human health considerations and studies from selected nonmammalian species representing different taxa drive environmental considerations, with limited cross-talk between the knowledge streams. The global regulatory landscape is experiencing an evolution in thinking surrounding animals in toxicity testing; in the US, for example, there is now a major drive to greatly reduce the use of in vivo testing. Therefore, the data landscape also is changing, requiring greater use of mechanistic, cell-based, and computationally derived information for consideration as alternatives to animal testing. To establish confidence in mechanistic data and provide evidence as to how it relates to apical-level changes at an individual or population level, the adverse outcome pathway (AOP) conceptual framework is being considered or actively adopted in many regulatory, industry, and academic settings. The AOP framework has been described as an approach for developing causal linkages between levels of biological organization, allowing for prediction of adverse effects. Such pathway-based approaches provide opportunities to incorporate data generated from all species and biological levels to understand the biology to mutually inform both human and environmental safety. This approach can be applied in considering both mammalian data to provide insights to nonmammalian species and vice versa. In fact, a critical component of the AOP framework is determining the taxonomic domain of applicability, with an emphasis on conservation (or lack thereof) of the biology and in particular pathways across species for the purpose of understanding how broadly available knowledge can be extrapolated. Fortunately, this shifting paradigm in toxicity testing has inspired the use of bioinformatics and specifically the development of tools and workflows for computationally exploring and predicting the taxonomic relevance of existing and newly generated toxicity data and knowledge across species. To date, a number of these methods/tools (e.g., SeqAPASS, EcoDrug, phylogenetic workflows) have been released to the public, peer-reviewed, and published. However, there is a growing recognition that although each tool brings important information to the challenge of cross-species extrapolation, maximum value in supporting decision-making can be achieved only when each individual tool is developed while considering its application in the context of, or alignment with, other approaches. Therefore, this session has been organized to enhance communication among researchers and decision-makers regarding interoperability and cooperation to advance the use of such computationally derived results to inform regulatory decisions.