P17-03 New approach methodologies to evaluate botanical safety

ABSTRACT

Natural products, such as botanical dietary supplements, are used globally and in some regions growing in their popularity and use, especially in the current COVID-19 pandemic. Ensuring the safety of these products is an important public health priority. Botanicals are naturally complex, with varying chemical compositions due to factors such as differences in growing conditions, extraction processes, and/or changes to the finished product. Globally, conventional in vivo and in vitro testing schemes are built on single chemicals, not on complex mixtures such as botanical products. Because of the chemical variability and a reliance on history of use data, toxicity data for many botanical mixtures are lacking and few tools have been tested for their suitability for these complex mixtures. A cross-sector collaboration between scientists in industry, government, and academia for botanical safety has been initiated with the goal of providing a sound scientific basis for integrating existing data with new approach methodologies to evaluate botanical safety. Thirteen botanicals with existing toxicity and/or clinical information available were chosen as initial candidates to evaluate various in silico and in vitro assays for their suitability to detect toxicological endpoints. Characterization of all thirteen botanicals was completed in early 2022, with quantification information obtained for selected individual constituents. Using this information as well as already available constituent details in the literature, the suitability of various in silico models and their use in various aspects of botanical safety evaluation were explored;as a screening step in an overall safety assessment for specific toxicological endpoints (e.g., genotoxicity, DART), to predict pharmacokinetic properties for use in PBPK modeling, and to predict formation of potentially toxic metabolites. Planned in vitro studies targeting specific endpoints of interest (hepatotoxicity, genotoxicity, developmental and reproductive toxicity, neurotoxicity, cardiotoxicity, and systemic toxicity) will be initiated mid-2022. This presentation will provide an overview of work completed to-date as well as a summary of the test materials, planned assays, and learnings to-date regarding advancements available for botanical safety assessment. Copyright © 2022 Elsevier B.V.