ToxCast Cytotoxicity-Associated Burst

Title: ToxCast Cytotoxicity-Associated Burst

Paragraph: Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Evaluating the ToxCast high-throughput screening library, many chemicals show activation of large numbers of assays over a narrow range of concentrations in which cell stress and cytotoxicity are also seen. We term this phenomenon the cytotoxicity-associated “burst”. Whereas some of the assay activity in this concentration range may represent chemical effects on the intended target of the assay, some of it is not. In such situations, activity represents a false positive response that can be ascribed to assay interference processes. This phenomenon raises the need to establish a concentration threshold at which each chemical begins to drive activity across multiple and diverse cell stress and cytotoxicity assays by initiating this cytotoxicity-associated burst of activity. Judson R, et al . Analysis of the Effects of Cell Stress and Cytotoxicity on In Vitro Assay Activity Across a Diverse Chemical and Assay Space. Toxicol Sci. 2016 Oct;153(2):409. doi: 10.1093/toxsci/kfw148. Epub 2016 Sep 7. Erratum for: Toxicol Sci. 2016 Aug;152(2):323-39. PMID: 27605417; PMCID: PMC7297301.

These data are based on ToxCast invitroDBv3.5