Computational Techniques to Quantify Chemical Similarity: Tools for Risk Assessment

Abstract

The principal goal of the cooperative agreement was to develop new molecular similarity methods and apply them to the risk assessment of environmental chemicals. To this end, our strategy had the following three-fold objectives: 1. Conduct an International workshop on " MOLECULAR SIMILARITY IN RISK ASSESSMENT " where internationally known experts in toxicology, computational chemistry, mathematical chemistry, structure-activity relationships and risk assessment of chemicals were brought together. These experts provided their opinions about how MOLECULAR SIMILARITY methods should be developed and used for risk assessment of chemicals. Ten experts were interviewed by the NRRI team and subsequently their input was summarized in a technical report submitted to USEPA. The workshop was part of QSAR ’92, an international conference held in Duluth, Minnesota jointly by the Natural Resources Research Institute-University of Minnesota and U S Environmental Protection Agency. The experts also submitted written manuscripts as part of the workshop. The workshop report reflected on different aspects of hazard assessment and molecular similarity. 2. Develop molecular similarity methodology by incorporating the inputs of the experts mentioned in item 1 above, along with our expertise in these methods. Special attention was given to the use of NONEMPIRICAL PARAMETERS (e.g., values calculated directly from the chemical structure) as opposed to empirical (or experimental) parameters because most chemicals used in the environment do not have experimental data necessary for detailed hazard assessment. 3. Apply the computational molecular similarity methods developed during the project in the selection of analogs and in estimation of environmentally important properties of these chemicals.