which OTC drugs in specific therapeutic classes would be generally recognized as safe and effective, and not misbranded (Category I). In the third phase, after considering the public comments received in response to ANPRs, the agency issued proposed rules designated Tentative Final Monographs. In the final step of the process, the agency, after receiving further comments, publishes final monographs. As of March 1, 2001, most, but not all, of these final monographs had been published (CDER, 2001). Final monographs set forth the mandatory conditions for an OTC drug to be considered generally recognized as safe and effective, and not misbranded, including active ingredients, dosages, permitted combinations of ingredients, warnings, and labeling requirements.
Under the New Chemicals Program, the Environmental Protection Agency (EPA) is given the authority to regulate the entry and use of new chemicals into the U.S. marketplace. This program, mandated by Section 5 of the Toxic Substances Control Act (TSCA) in 1976, seeks to manage the potential risk from new chemicals both to humans and to the environment. Manufacturers or importers of new chemicals are required under TSCA to notify EPA through a premanufacturer notice (PMN) that must be submitted at least 90 days prior to manufacture or import of the new chemical. New chemicals are defined as those that are not listed on EPA’s TSCA Chemical Substance Inventory of existing chemicals. The burden of proof for identifying risk rests with EPA.
EPA receives petitions for approximately 2,000 new chemicals from manufacturers each year (Personal communication, L. Scarano, EPA, October 11, 2001). At submission, the manufacturer provides the PMN, which includes information on chemical and physical identity and properties, product uses, proposed production or importation volume, by-products, human exposure, disposal practices, environmental releases, pollution prevention efforts, and available information on health or environmental effects. A multidisciplinary team of experts is responsible for reviewing the safety information provided in the PMN. The first step is to determine whether the substance is already on the TSCA inventory. If it is not, the team then evaluates chemical structure, how the chemical is synthesized, the intended use of the chemical, and the physical and chemical properties of the chemical. They also check for analogs in an EPA analog database. About 30 percent of the applications are not reviewed after this stage; these substances consist of polymers, which because of their molecular weight and other properties are considered unlikely to present significant hazard potential.
The next step of the process is to estimate the potential environmental