Characterizing chlorotriazine effects in cancer-relevant high-throughput screening assays

There were common targets consistently identified as bioactive across the chemical class including induction of estrone levels and potential CAR/PXR activation. These findings were put in context by utilizing <i>in vivo</i> data and knowledge about atrazine to weigh the evidence. Though the ToxCast/Tox21 HTS mechanistic assays did not yield novel insights into chlorotriazine carcinogenicity, our workflow exemplifies how starting from mechanistic screening data and integrating apical endpoints can be conducted. By providing context to <i>in vitro</i> ToxCast/Tox21 data with toxicokinetics information and available <i>in vivo</i> study outcomes demonstrates how the HTS data and KCC framework can be applied to review a chemical class for carcinogenicity potential.