Incorporation of In Vitro Techniques for Botanicals Dietary Supplement Safety Assessment – Towards evaluation of Developmental and Reproductive Toxicity (DART)
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ABSTRACT: As complex mixtures, botanicals present unique challenges when assessing safe use, particularly when endpoint gaps exist that cannot be fully resolved by existing toxicological literature. Obtaining data for developmental and reproductive toxicity (DART) can be particularly difficult as this is a frequent data gap for botanicals. Here we explore in vitro receptor binding and enzyme activity assays as well gene expression studies as alternative tools to inform on DART relevent modes of action. Botanicals suspected to have DART effects in addition to herbs with a significant history of use were tested at biologically relevant doses to probe activity at a molecular level. Additionally, gene expression changes in a number of different cell types were analysed using the connectivity mapping approach (CMap) to identify modes of action through a functional read across approach. Together, these two data streams increase the confidence in predictions of biological mode of action and inform potential DART risk by way of potency comparisons and/or a margin of internal exposure approach.
ORGANISM(S): Homo sapiens
PROVIDER: GSE144235 | GEO | 2020/05/01
REPOSITORIES: GEO
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