Each year many new chemicals join the thousands already in existence in the marketplace. Determining their potential hazard to humans and the environment is an ongoing challenge for the EPA's mission of sustainability in support of economic growth. At the EPA's National Risk Management Research Laboratory (NRMRL), sustainability scientists are developing new computer tools that estimate the toxicity of the molecular structure of chemicals using quantitative structure-activity/property relationships (QSARs). These QSAR techniques yield faster and cheaper results than traditional experimental testing, which is currently being reduced or banned in the United States and European Union. The new QSAR-based Toxicity Estimation Software Tool (T.E.S.T.) will be released in a freely available format this year. Background The demand for toxicological testing has grown significantly along with increasing public and governmental concern for the safety of new drugs and industrial chemicals. EPA's New Chemicals Program was established in 2007 to identify and control new chemical substances. The New Chemicals Program functions as a gatekeeper that can identify conditions, up to and including a ban on production, to be placed on a new chemical before it enters the marketplace. Under this program, manufacturers must provide test data on new chemicals detailing their risk of carcinogenic, mutagenic, acute, and chronic effects on human health. Environmental test data must show acute toxicity to invertebrates and fish, as well as bioaccumulation data (long-term environmental effects). In the absence of the manufacturer's own test data, EPA testing procedures use QSAR models to predict the toxicity of new industrial chemicals. QSAR models express the correlation between the chemical's physicochemical properties and its toxicity. EPA's ECOSAR (Ecological Structure Activity Relationship) software uses more than 100 QSAR models for 42 different chemical classes to estimate the toxicity of industrial chemicals to aquatic organisms such as fish, invertebrates, and algae. However, because these models are not species-specific, NRMRL sustainability researchers are developing molecular structure software that can be used to estimate toxicity for specific species. For example, the new software tool estimates the concentrations of chemicals in water that will kill half of a specific fish population (i.e., fathead minnows) in a four-day period. The software estimates toxicity directly from molecular structure, and no animal testing is involved. The new software tool will allow the user to simply input a chemical to be evaluated by drawing it in a sketcher window, entering a SMILES (Daylight Chemical Information System 2006) string, or by entering other standardized formats for molecular structures. Once entered, the program calculates the molecular descriptor values and then estimates the toxicity. It is expected that the tool will aid regulatory agencies and industry with assessing chemicals for programs such as EPA's New Chemicals Program. Five validated QSAR methodologies are included in the new T.E.S.T. software tool. They are detailed at the Clean Processes Program's QSAR web page (www.epa.gov/nrmrl/std/cppb/qsar/index.html). Readers who are interested in a full report and discussion of the QSAR methodologies used in the program research will find information in: Martin, T.M., P. Harten, R.Venkatapathy, S. Das, and D.M. Young. (2008). "A Hierarchical Clustering Methodology for the Estimation of Toxicity." Toxicology Mechanisms and Methods, 18, 2: 251-266. For more information: Jane Ice, NRMRL Office of Public Affairs, 513-569-7311.
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