You are here:
ICACSER Team Kickoff Meeting
Citation:
LaLone, C., N. Basu, P. Browne, S. Edwards, M. Embry, F. Sewell, AND G. Hodges. ICACSER Team Kickoff Meeting. ICACSER SETAC Sponsored Webinar, NA, MN, June 22, 2022. https://doi.org/10.23645/epacomptox.20493123
Impact/Purpose:
This presentation is an introduction of the International Consortium to Advance Cross-Species Extrapolation in Regulation and specifically to describe the teams that will begin implementing tasks within the Consortium. The motivation for developing the consortium, relative to reducing the use of animals in toxicity testing, increasing efficiencies in understanding chemical safety, and taking advantage of existing data/knowledge will be described. Additionally, needs for species extrapolation and current methods will be discussed. A path forward for the consortium to focus on the use of bioinformatics approaches for cross species extrapolation will be described, including tasks of defining the regulatory landscape, developing a bioinformatics toolbox, and communicating the science to stakeholders.
Description:
The global regulatory landscape surrounding chemical safety is shifting away from animal testing and moving toward greater reliance on New Approach Methodologies (NAMs) including a rapid growth in molecular data and computational methods to achieve human and environmental protection goals. This change presents both new hurdles and opportunities for advancing NAMs focused on a non-animal testing agenda and accelerating them into mainstream regulatory decision-making. One of the challenge in this regard is understanding how existing data on effects observed in few species, typically model test species, translate to the diversity of life and so can be used as surrogate information across a broader biological domain, reducing the need for additional data generation. The adverse outcome pathway (AOP) conceptual framework and descriptions of the taxonomic domain of applicability for key events (KEs) and key event relationships (KERs) through the biological levels of organization provide an opportunity to integrate evidence of structural and functional conservation, which can be gleaned from computational methods. To capitalize on advances in OMICs technologies and take advantage of existing toxicity data that can be generated without the use of whole animal models (e.g., high throughput screening and transcriptomics data, in vitro, and fish embryo testing), approaches in bioinformatics are starting to demonstrate application for cross species extrapolations. Bioinformatics applies computational techniques to understand and organize information associated with molecules, including sequence and structural alignments, phylogeny evaluations, prediction of protein structures and function, gene annotation, and gene expression analyses, as examples, to understand biology and biological pathways. Advances in bioinformatics have begun to inform chemical safety evaluations, specifically informing species extrapolation. Tools and methods for species extrapolation that are built with bioinformatic approaches have been peer reviewed, published, and publicly accessible to enable their use in research and regulatory decision-making. To advance cross species extrapolation with an objective to inform a 21st century regulatory non-animal testing agenda for assessing human and ecological health, a global, cross-sector consortium has been created with the researchers, regulators, and advocates working toward integration of approaches in bioinformatics. knowledge for a larger diversity of species it is timely to bring together a global consortium to focus efforts. While recognizing the importance of toxicokinetics in understanding and applying cross species extrapolation approaches, the primary initial focus of the consortium is on capitalizing on the rapidly expanding opportunities in bioinformatics methods for advancing regulatory decision-making. If successful, this will allow risk assessors to make better use of existing toxicological information and more easily consider the impact of chemicals on a variety of species.
URLs/Downloads:
DOI: ICACSER Team Kickoff Meeting
ICACSER_TEAM MEETING_6_22_22.PDF (PDF, NA pp, 3324.743 KB, about PDF)