Of the approximately 80,000 chemicals used in commerce in the United States, few have been tested, and only a fraction have sufficient publicly available data to allow a thorough evaluation of risk. Businesses, governmental organizations, and other stakeholders often don't have the data necessary to identify problem chemicals or identify safer substitutes or other options that are less risky, prevent pollution, and may save companies environmental management costs. At times, companies must make product and process decisions without enough data regarding the risk tradeoffs. The Office of Pollution Prevention and Toxics (OPPT) has developed computer-based methods that derive important risk assessment information based on chemical structure, conservative defaults, standard scenarios, and other factors. These methods provide information on physical/chemical properties, environmental fate, potential carcinogenicity, toxicity to aquatic organisms, worker and general population exposures, among other data. OPPT routinely uses these methods to highlight chemicals of concern, to identify safer substitutes, and to reduce or eliminate risks. The Pollution Prevention Framework (P2 Framework) is compilation of many of OPPT's most important computer-based methods for predicting risk-related information. The P2 Framework provides important methods to predict risk-related information that may not be readily available. Its purpose is to provide information that can inform decision making and help promote the design, development, and application of safer chemicals, products, and processes. The document describes each methodology and the importance of the data generated, and provides case studies showing how methods can be used collectively to answer complicated risk assessment questions and identify pollution prevention opportunities. The P2 Framework, as currently constructed, does not address all biological endpoints. It is a set of screening-level methods that are of most value when chemical-specific data are lacking.