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Developmental Toxicity Testing of Gaseous Chemicals with a Human Pluripotent Stem Cell-Based Assay

Presented at the Teratology Society Annual Meeting in San Diego, California (June, 2019)

Innovative in vitro toxicity screening assays aimed at reducing or replacing the use of animals in chemical safety testing are critical to meet the safety requirements across industries. Multiple publications have demonstrated the applicability of various in vitro assays for evaluating the developmental toxicity potential of non-volatile chemicals; however, very little information is available regarding application of these assays to volatile chemicals (e.g., gases).

DevTOX quickPredict (devTOXqP) is an in vitro human pluripotent stem cell (hPSC)-based assay that predicts the developmental toxicity potential of chemicals based on changes in ornithine and cystine metabolism. devTOXqP is highly concordant (~85%) with human and animal developmental toxicity outcomes across diverse chemotypes.

The objective of this study was to modify the devTOXqP hPSC culture methods to test volatile and gaseous chemicals using Tedlar bags and evaluate the potential of chemicals tested in this system to induce a metabolic response in hPSCs. The applicability of the Tedlar bag culture methods was evaluated with four gaseous chemicals that have known developmental toxicity outcomes in vivo (HFC-236fa, HFC-245fa, acetaldehyde, and hexafluoroacetone).

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