Two new papers describe publicly accessible web-based tools for exploring environmental chemicals and predicting their risk. These resources will help health policymakers to make faster and more accurate decisions about chemical safety and the need for remediation efforts.
The Conditional Toxicity Value (CTV) Predictor, was described in the May issue of Environmental Health Perspectives. The tool’s web portal allows users to rapidly obtain chemical toxicity values, which are predicted using a collection of statistical models.
The second tool was reported May 22 in the journal Bioinformatics. The ChemMaps.com webserver allows users to easily browse, navigate, and mine chemical space. ChemMaps.com includes DrugMap, which lists more than 8,000 drugs, and EnvMap, which lists more than 47,000 chemicals of relevance to NIEHS and the U.S. Environmental Protection Agency (EPA).
“For environmental chemicals, we can now visualize the areas of chemical space where we have safety data and where there are clusters of toxic or nontoxic chemicals,” said Nicole Kleinstreuer, Ph.D., co-author of the ChemMaps study. Kleinstreuer is the deputy director of the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).
“[This will] facilitate green chemistry applications, help prioritize allocation of testing resources, and allow predictions on new chemicals,” she explained.
Filling a critical gap
According to the authors of the Environmental Health Perspectives paper, of the tens of thousands of chemicals in commerce or on various manufacturing inventories, only hundreds have comprehensive toxicological data or have undergone some form of human health risk assessment.
In 2009, the National Academies of Science Engineering and Medicine recommended “development of default approaches to support risk estimation for the large number of chemicals lacking chemical-specific information.”
To address this need, researchers proposed a solution for predicting toxicity values for data-poor chemicals through the development of quantitative structure–activity relationship (QSAR) models. To develop the models, they used a comprehensive database of chemicals with existing regulatory toxicity values from U.S. federal and state agencies.
“It provides a rapid first approximation that can be used for the vast majority of chemicals for which a traditional toxicity value has not been derived yet,” said study co-author Ivan Rusyn, Ph.D., M.D., from Texas A&M University and an NIEHS grantee.
The CTV Predictor web portal allows users to complete a search in less than one minute, making it especially useful in emergency situations (see sidebar).
“CTV Predictor fills a huge gap in our ability to make informed decisions about the safety of chemical exposures, particularly in cases where a rapid answer is needed,” said senior author Weihsueh Chiu, Ph.D., also from Texas A&M University.
Exploring chemical space
Chemical databases are continuing to grow in size and diversity. Yet they have remained largely inaccessible to nonspecialists due to the complicated analysis techniques required to explore them. To address this problem, researchers from North Carolina State University (NCSU) developed the first fully interactive, easy-to-use tool for rapidly navigating chemical space.
The first version of ChemMaps.com, released Dec. 20, 2017, focused on the chemical space defined by more than 8,000 drugs from the DrugBank database. An expanded version, released Feb. 1, includes environmental chemicals with toxicological categorizations derived from animal study data. Future versions will include additional data, such as that from predictive high-throughput screening assays.
“In terms of public health policy, ChemMaps.com can help to visualize a large set of chemicals, visualize applicability domains of various prediction models for different human health endpoints, and overlay different data sets to help inform chemical prioritization, and potentially, even risk assessment,” said first author Alex Borrel, Ph.D.
Now a postdoctoral fellow in the NIEHS Biostatistics and Computational Biology Branch, Borrel was in the NCSU lab of senior author Denis Fourches, Ph.D., at the time of the study.
Borrel A, Kleinstreuer N, Fourches D. 2018. Exploring drug space with ChemMaps.com. Bioinformatics doi: 10.1093/bioinformatics/bty412.
National Research Council Committee on Improving Risk Analysis Approaches Used by the U.S. EPA. 2009. Science and Decisions: Advancing Risk Assessment. Washington (DC): National Academies Press.
Wignall JA, Muratov E, Sedykh A, Guyton KZ, Tropsha A, Rusyn I, Chiu WA. 2018. Conditional Toxicity Value (CTV) Predictor: An in silico approach for generating quantitative risk estimates for chemicals. Environ Health Perspect 126(5):057008.
(Janelle Weaver, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)