Comparative Requirements for Premarketing Premanufacture Notifications in the EC Countries and the USA, with Special Reference to Risk Assessment in the Framework of the US Toxic Substances Control Act (TSCA)

Abstract

The legal-scientific control system for toxic substances is embodied in the 79/831 EC Directive in the European Community countries and in the Toxic Substances Control Act (TSCA) in the United States. The 6th Amendment of the EC Directive and Section 5 of TSCA cover notification of new chemicals and require a Premarketing Notification and a Premanufacture Notification, respectively (both known as PMN). Beyond a commonality of some general information required in the submission on a new chemical (such as chemical identity and molecular structure, proposed categories of use, production or importation level) there are two important differences between the two systems. First, the EC Directive requires as a mandatory part of a PMN submission a specified “base set” of health, environmental, and physicochemical test data; TSCA Section S does not specify a set of mandatory test data but requires, as a part of the PMN submission, data on all health and environmental effects in the possession or control of the notifier, as well as on byproducts, resulting from the manufacture, processing, use, or disposal of the new chemical. Second, the EC Directive is not concerned with either controlling the potential adverse health and environmental effects of a new chemical or with the assessment of risk that these effects represent; these issues are left up to the EC member states to legislate and handle. Forty-five days after submission of an EC PMN, if all notification requirements have been met and if the packaging and labeling requirements comply with the Directive, the chemical may be placed on the market. In TSCA, companies must notify the US EPA 90 days before they intend to begin the manufacturing or importation of a new chemical for commercial use. The 90 days (which may be extended under TSCA to 180) is used by EPA to carry out an initial assessment of the health and environmental risk that the chemical may represent. Should a “reasoned evaluation” of the data submitted and/or otherwise available indicate that the chemical could or does present an “unreasonable risk to health and the environment,” the Agency can, under Sections 5(e) and 5(f), respectively, limit or prohibit the production, use or disposal of the chemical. Both the EC Directive and TSCA mandate the establishment and publication of Inventories of chemicals. The EC Directive Inventory is a closed system, listing only those chemicals which were on the EC market during specified reporting periods; chemicals submitted subsequently will remain “new” so that each subsequent manufacturer or importer must submit a PMN. In contrast, the TSCA Inventory keeps on continuously increasing by those PMN chemicals, the manufacture or importation of which has actually begun. The TSCA assessment framework for chemicals makes a clear distinction between hazard and risk. The hazard of a chemical represents its suspected or established inherent toxicological capabilities to inflict damage on the health of humans, animals, plants, and the environment at-large, through some type of exposure. There is risk, when there is actual exposure to a hazardous chemical; in other words, risk of chemicals represents the overlap of hazard and exposure. The overall process of PMN assessment in the US EPA includes a first phase of risk assessment and a second phase of regulatory disposition. In accordance with the distinction made between hazard, exposure and risk, the stage-setting initial evaluation of PMNs is carried out along two converging procedural channels (representing hazard assessment and exposure assessment) in the risk assessment stage. Following the convergence of the outcomes of the hazard and exposure assessments, the level of risk that a new chemical may represent determines the regulatory disposition (if any) taken subsequently. A key component of the hazard assessment of PMN chemicals at EPA resides in the Structure-Activity Team (SAT). SAT assesses PMNs against a hazard evaluation grid, representing data or estimate categories on chemical and physiocochemical properties, environmental fate, bioaccumulation, irritant properties toward and absorption into living organisms, acute and chronic toxicological and pharmacological effects, generation of xenobiotic metabolic split products, impurities present,, etc. The hazard rating of PMN chemicals (into those of low-, medium-, and high-level concern) is based on a combination of three approaches or data source categories: (a) evaluation of the test data and related information submitted; (b) evaluation of the xenobiotic and/or pharmacological potentialities of the compound regarded singly, as distinct from its possible analogy to other compounds; (c) structure-activity relationship analysis, based on structural analogy to compounds or classes of compounds established to have xenobiotic effects. Only chemicals of substantial concern are led through all steps of the assessment process. Submissions on certain categories of PMN chemicals (e.g., certain water-insoluble high polymers, low/medium hazard level photographic chemicals incorporated into films) receive special procedural treatment and undergo limited assessment.