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 will employ 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.

EPA’s chemical transformation simulator: A tool for prediction of metabolites and environmental transformation products

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.