ToxStrategies scientists published a study in Toxicological Sciences aimed at contributing to the understanding of Cr(VI) MOA by evaluating high-throughput screening (HTS) data and other in vitro data relevant to Cr(VI), and comparing these findings to robust in vivo data, including transcriptomic profiles in target tissues. Emerging methods were used to evaluate the HTS data, including mapping of assays to the proposed Ten Key Characteristics of Carcinogens (TKCCs), incorporation of potential cytotoxicity interference, and comparison to other publicly available in vitro data to support findings. Comparing in vitro responses to in vivo transcriptomic responses, similarities were identified between cell death/proliferation alterations occurring in response to Cr(VI). Differences in p53/DNA damage signaling pathway alterations were apparent, with p53 pathway changes occurring in vitro but not in vivo. This example therefore informs potential ranges of applicability for the utility of HTS in predictive toxicology.
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