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Review: Endogenously Produced Volatiles for In Vitro Toxicity Testing Using Cell Lines
Citation:
Winters, B., J. Pleil, J. Boyer, L. Nylander-French, M. Ariel Wallace, AND Michael C. Madden. Review: Endogenously Produced Volatiles for In Vitro Toxicity Testing Using Cell Lines. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, 4(2):1-10, (2018).
Impact/Purpose:
Due to increasing emphasis on in vitro toxicity testing, particularly high-throughput screening (HTS), there is significant interest in determining whether rapidly monitoring for alterations in endogenously produced volatiles (EPVs) in vitro can identify chemicals of concern. However, limited research has been conducted on how EPVs may be altered when mammalian cell cultures are exposed to xenobiotics. Therefore, to determine whether EPVs are viable biomarkers of cellular responses, including cytotoxicity, background EPVs must first be characterized. Upon characterization of background volatiles, xenobiotic-induced alterations of EPVs, if any, can then be identified. Here, we focus on analyzing the formation of endogenous metabolites as a novel method for toxicity screening of household, pharmaceutical, and environmental agents for toxicity.
Description:
Due to the approximately 86,000 chemicals registered under the Toxic Substances Control Act and increasing ethical concerns regarding animal testing, it is not economically or technically feasible to screen every registered chemical for toxicity using animal-based toxicity assays. To address this challenge, regulatory agencies such as the United States Environmental Protection Agency (U.S. EPA) are investigating high-throughput screening (HTS) in vitro methods to increase speed of toxicity testing while reducing the overall cost. One approach for rapid toxicity testing currently being investigated is monitoring of volatile emissions produced by cell lines in culture. Such a metabolomics approach would measure gaseous emissions from a cell line and determine if such gaseous metabolites are altered upon exposure to a xenobiotic. Herein, we describe the history and rationale of monitoring endogenously-produced volatiles for identification of pathologic conditions as well as emerging applications in toxicity testing for such an approach.
