You are here:
EPA’s Chemical Transformation Simulator: A Tool for Prediction of Metabolites and Environmental Transformation Products
Citation:
Stevens, C., R. Gladstone, J. Lazare, N. Pope, E. Weber, AND K. Wolfe. EPA’s Chemical Transformation Simulator: A Tool for Prediction of Metabolites and Environmental Transformation Products. 2021 ACS Fall Meeting, Atlanta, GA, August 22 - 26, 2021.
Impact/Purpose:
Manufactured chemicals are often transformed into different molecules in environmental and biological systems, and the resulting transformation products generally differ from the parent chemical in their toxicity and physicochemical properties. ORD has developed the Chemical Transformation Simulator (CTS) as a web-based tool for predicting environmental and biological transformation pathways and physicochemical properties of organic chemicals. This tool can help chemical assessors anticipate potential impacts to humans and ecological species from exposure to manufactured chemicals and their degradates/metabolites.
Description:
The Chemical Transformation Simulator (CTS, https://qed.epa.gov/cts/) developed by EPA’s Office of Research and Development is a web-based screening tool to evaluate organic chemicals for their potential to degrade in the environment or be transformed through metabolism. CTS predicts the formation of products by searching for structural fragments within a molecule that are susceptible to transformation and then modifying that fragment according to one or more reaction schemes encoded in a collection of libraries. CTS reaction libraries have been developed to predict the products that form from environmental transformation processes, including hydrolysis, abiotic reduction, direct photolysis, and anaerobic biodegradation. Additionally, CTS makes available potential human phase 1 metabolites, as predicted by ChemAxon’s Metabolizer reaction library. Through programmatic linkages to the BioTransformer (http://biotransformer.ca/) tool for the prediction of small molecule metabolism, CTS provides additional predicted metabolites in mammals and their gut microbiota. Finally, CTS employs webservice linkages to the EnviPath (https://envipath.org/) tool to retrieve predicted aerobic biodegradation products. Molecules with numerous sites that may be subject to transformation pose a particular challenge for metabolite prediction tools, because the number of potential products can grow exponentially with each generation of predictions. CTS reaction libraries minimize this potential for combinatorial explosion by employing various strategies to identify the most likely transformation products. These strategies include the semi-quantitative ranking of reaction schemes based on reported observed transformation rates and the use of reaction rules to constrain reactivity and/or identify the most likely transformation site among structurally similar fragments within a molecule. Expanding regulatory assessments of new chemicals to consider the most likely predicted metabolites and environmental transformation products can provide a more holistic evaluation of the potential impacts to humans and ecological species.
