Comment on "On the Utility of ToxCast™ and ToxPi as Methods for Identifying New Obesogens"

In the mBMSC assay, the data were more consistent between adipogenesis and gene induction, but they disagree qualitatively and quantitatively with the 3T3-L1 findings. [...]it is not clear how one could definitively compare the results from the Janesick et al. study to the ToxCast™ and Tox21 results on an individual assay basis. In considering all of the ToxCast™ data, it is evident that triphenyltin is highly cytotoxic and invokes cellular stress pathways and cell death across numerous cell types with submicromolar potency. [...]it can be difficult to capture specific target activity in cell-based assays when general cytotoxicity is occurring at similar concentrations, which appears to be the case for the ToxCast™ RXRα assay. [...]structurally diverse libraries are screened in lead-generation activities in the pharmaceutical industry. [...]Janesick and colleagues concluded with a recommendation for eliminating the averaging of results across assays in favor of eliminating poorly performing assays.