In an article entitled “Study questions EPA ToxCast’s ability to identify endocrine disruptors”, published on February 1, 2016 at the Inside EPA online news website, Maria Hegstad reports on a scientific study by Amanda Janesick and co-workers from the University of California, Irvine (UCI), U.S., published in the peer-reviewed journal Environmental Health Perspectives on January 13, 2016.
The ToxCast, short for Toxicity Forecaster, is a large screening program run by the U.S. Environmental Protection Agency (EPA) that relies on a large collection of high-throughput in vitro screening assays to identify potentially toxic chemicals (FPF reported). ToxCast data are meant to be used by scientists worldwide to prioritize chemicals likely to act through specific pathways of interest (FPF reported). However, Janesick and colleagues’ study demonstrates that the cellular screening data collected within ToxCast does not allow a clear identification of a group of obesogenic chemicals that function through peroxisome proliferator-activated receptor gamma (PPARγ). Only five of the 21 PPARγ-activating chemicals scoring highest in ToxCast could be confirmed by the UCI researchers.
The authors have also calculated a Toxicological Priority Index (ToxPi) for adipogenesis using ToxCast assays thought to predict adipogenic chemicals (including pathways other than PPARγ). The ToxPi is a publicly available EPA-designed tool for comparing chemical properties, toxicity and exposure predictions. Out of 17 chemicals with a high adipogenesis ToxPi, only 7 were shown to be adipogenic in laboratory assays. Moreover, 2 out of 7 predicted negatives were adipogenic as well. The authors concluded that for PPARγ activation and adipogenic potential “a modest predictive value of ToxCast” was observed, making it likely that “many obesogenic chemicals remain to be identified.”
These findings come at a time when EPA is proposing to use ToxCast toxicity screens as substitutes for Tier 1 assays employed in its Endocrine Disruptor Screening Program (EDSP) (FPF reported). In light of this, several concerns were raised by Bruce Blumberg, senior author of the study on obesogens, and his colleagues. In particular, researchers worry about the recurring discrepancies between ToxCast’s findings and more traditional toxicity testing methods, as well as the lack of agreement between different ToxCast assays focused on the same endpoint. They also raise concerns about insufficient quality control of the ToxCast data obtained from external contractors and point out that additional screening levels should be added in order to reduce the high number of false positives and false negatives.
Janesick, A. et al. (2016). “On the utility of ToxCast and ToxPi as methods for identifying new obesogens.” Environmental Health Perspectives (published online January 13, 2016).