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Reply to “Comment on ‘On the Utility of ToxCast™ and ToxPi as Methods for Identifying New Obesogens’”
Amanda S. Janesick, Giorgio Dimastrogiovanni, Raquel Chamorro-Garcia, and Bruce Blumberg
Janesick and colleagues recently published an evaluation of the utility of ToxCast™ and Tox21 bioactivity data for predicting PPARγ activation and induction of adipogenesis. As providers of the ToxCast™ and Tox21 data as well as some of the chemicals employed in their follow-up study, we would like to comment on the methods Janesick and colleagues used in their application and interpretation of the data with respect to: 1) incorrect ToxCast™/Tox21 citations in the main text of the article; 2) lack of consideration of methodological, platform, and reagent differences when comparing the performance of individual ToxCast™ and Tox21 assays with their targeted studies; 3) inconsistencies in some of the results reported by Janesick and colleagues on an individual assay basis; 4) conclusions on the relative selectivity of the RXR-active chemicals; 5) lack of consideration of technical and statistical factors; and 6) incorrect integration of corollary data.
Through the ToxCast™ and Tox21 programs, the U.S. Environmental Protection Agency (EPA), National Toxicology Program (NTP), and National Center for Advancing Translational Sciences (NCATS) are committed to providing free and public data to support predictive toxicology efforts aimed at evaluating the potential hazard of environmental chemicals and facilitating scientific dialogue around the approach. We note that many of the data from ToxCast™ and Tox21 have been published in peer-reviewed journals, including the assay systems used in the study by Janesick et al. This includes, with correct citations, the NovaScreen cell-free biochemical assay platform (Knudsen et al. 2011; Sipes et al. 2013), the Attagene multiplex reporter gene assay platform (Martin et al. 2010), and the Tox21 reporter gene assays (Huang et al. 2011). The raw and processed ToxCast™ and Tox21 data and the computer code used to analyze the data can be downloaded from our website (https://www.epa.gov/chemical-research/toxicity-forecaster-toxcasttm-data). The processed data can also be accessed using the iCSS ToxCast™ Dashboard (https://actor.epa.gov/dashboard/). In addition, lessons learned from ToxCast™ Phase I have been thoroughly reviewed (Kavlock et al. 2012) in setting the path for ToxCast™ Phase II.
The analysis performed by Janesick and colleagues focused heavily on comparing the results from several ToxCast™ and Tox21 assays with...