Cross-sector Partnership Uses Advanced Non-Animal Approach to Better Understand Chemical Effects

The US Environmental Protection Agency’s (EPA) New Chemicals Collaborative Research Program (NCCRP) is exploring the use of modern tools to help the agency efficiently and effectively make decisions about chemicals that better protect health and the environment.

EPA’s Office of Pollution Prevention and Toxics (OPPT) is required to make rapid decisions about whether to allow companies to bring new industrial chemicals to market. A 2016 legal mandate, driven by technological advances, emerging science, and an ethical obligation and public desire to reduce animal testing, requires OPPT to use non-animal testing during its assessments whenever possible. As part of the NCCRP, OPPT and EPA’s Office of Research and Development have teamed up to develop a proof-of-concept non-animal testing approach to rapidly generate chemical data to better understand potential chemical effects and aid in making rapid, science-based decisions. This proof-of-concept was positively reviewed by a federal advisory committee, known as the EPA’s Board of Scientific Counselors, in Fall 2022.

The proof-of-concept integrates information from multiple methods including an in vitro pharmacology assay panel that provides information on chemical activity for 50 potential molecular targets. These targets are relevant to endocrine, development and reproductive, neurological, cardiac, and metabolic pathways, including binding to or activation of human cellular receptors, and interaction with ion channels and other enzymes. As a first step, ORD plans to test 100 Toxic Substance Control Act (TSCA)-relevant chemicals and reference chemicals as a proof-of-concept in 2024. PETA Science Consortium International e.V. is providing $110,000 in funding to test an additional ten chemicals.

The data will be analyzed to assess how the in vitro pharmacology assay panel can be applied to rapidly generate toxicity data to be used in a weight-of-evidence approach to help understand the potential toxicity of chemicals to humans. When enough data are collected, they could also be used to predict the health effects of other, similar chemicals using read-across and quantitative structure-activity relationship models. The in vitro pharmacology assay panel, when combined with other new approach methods for hazard and toxicokinetics, could inform assessments of new chemicals with little to no known hazard information.

Once blinded testing is complete at the contract research organization, Eurofins, the raw data will go through the EPA ToxCast data analysis pipeline and eventually be publicly released through EPA’s ToxCast database (invitroDB). This effort represents the latest in a series of collaborative efforts among scientists and regulators to improve the efficiency and effectiveness of chemical assessments to best protect humans and the environment.