Risk assessment of existing chemicals

While participating in the European Union programme on risk assessment of existing chemicals, Euro Chlor (representing all major European chlorine producers), recognised the need to carry out a detailed risk evaluation on chemicals linked to the production of chlorine. In view of concerns about specific risks of organohalogen compounds to the marine environment as a sink for all watercourses, Euro Chlor focused on this environmental compartment, with emphasis on the North Sea. This sea area has been extensively studied and is controlled by the Oslo and Paris Convention for the Prevention of Marine Pollution (OSPARCOM). For a series of chemicals on lists of concern adopted by the North Sea Conference (1990), risk assessments are being carried out to demonstrate their variable environmental profiles. 

Some of these side effects may be impossible to detect either in vivo or using alternative model systems nevertheless, the availability of models that would be predictive of neurotoxic effect is of great relevance for the risk assessment of existing chemicals and of new molecular entities. In vivo testing guidelines for neurotoxicity and developmental neurotoxicity have been developed, implemented, and validated. Though there is still room for improvements and refinements, these in vivo tests have been shown, so far, to provide reliable indications on the potential neurotoxicity of chemical substances. However, such in vivo tests are time consuming and expensive and require the use of a substantial number of animals. 

EUCLID is operated by the European Chemicals Bureau which, in turn is part of the EC Joint Research Centre s Environmental Institute. This newly-established database will receive, process and store all the data submitted by industry in accordance with existing Chemicals Regulations. The Bureau will use data in EUCLID to harmonise procedures for priority setting and risk assessment of existing chemicals. From 1994 the Bureau will also... 

Technical Guidance on Risk Assessment of Existing Chemicals in Accordance with the Requirements of Council Regulation 93/793/ EEC (July 1994 Draft), German UBA. 

EC (1996) Technical guidance document in support of the Commission directive 93/67EEC on risk assessment for new notified substances and Commission regulation 1488/94 EEC on risk assessment for existing chemicals. Brussels, European Commission. 

European Commission (1996) Technical Guidance Documents in support of Directive 93/67/EEC on risk assessment of new notified substances and Regulation (EC) No. 1488/94 on risk assessment of existing substances (Part I, n, III and IV). The European Commission Luxembourg European Commission. The white paper on Chemical Strategy, COM (2001) 88. European Commission Luxembourg... 

A similar situation exists for the hazard assessment of environmental pollutants. More than 15 million distinct chemical entities have been registered with the Chemical Abstract Service and the list is growing by nearly 775,000 per year. About 1000 of these chemicals enter into societal use every year. Few of these chemicals have experimental properties needed for risk assessment. Table 1 gives a partial list of properties necessary for a reasonable risk assessment of a chemical. In the United States, the Toxic Substances Control Act Inventory has about 74,000 entries and the list is growing by nearly 3000 per year. Of the approximately 3000 chemicals... 

The Existing Substances Regulation passed in 1993 initiated the assessment of existing chemicals. This effort compiled existing information on nearly 3,000 high production volume chemicals and almost 8,000 low production volume chemicals. There were 141 substances identified for risk assessment. Some of these substances were regulated under the Limitations Directive. 

Transportation should be considered when assessing risks associated with planned or existing plants. The design of new chemical processing units should include at the earliest opportunity a qualitative or quantitative risk assessment of the whole system including production, use, and transportation in order to minimize overall risk. A brief discussion of the inherent safety aspects of transportation is included in Chapter 5. 

Most of the provisions of the Toxic Substances Control Act (TSCA) of 1976 (PL 94-469) rely in some way on risk assessment of chemicals. Under the reporting requirements of the statute, any manufacturer, processor, or distributor of a chemical for commercial purposes must inform the EPA immediately after discovering any information which "reasonably supports the conclusion" that a chemical substance or mixture "presents a substantial risk of injury to health or to the environment" unless the EPA Administrator has been adequately informed already. EPA is mandated to establish regulations for testing new or existing substances when it is determined that there is not enough health or environmental information, that testing is necessary to develop such information and that the chemical or mixture "may present an unreasonable risk of injury to health or the environment."... 

In order to achieve that an environmental fate model is successfully applied in a screening level risk assessment and ultimately incorporated into the decisionmaking tools, the model should have computational efficiency and modest data input. Moreover, the model should incorporate all relevant compartments and all sources of contamination and should consider the most important mechanisms of fate and transport. Although spatial models describe the environment more accurately, such models are difficult to apply because they require a large amount of input data (e.g., detailed terrain parameters, meteorological data, turbulence characteristics and other related parameters). Therefore, MCMs are more practical, especially for long-term environmental impact evaluation, because of their modest data requirements and relatively simple yet comprehensive model structure. In addition, MCMs are also widely used for the comparative risk assessment of new and existing chemicals [28-33]. 

Another balance of factors within TSCA has to do with the risks and benefits of the far larger number of existing chemicals. E.H. Blair s contribution examines the problem of setting priorities for testing exsiting chemicals to assess their risks in a cost-effective procedure. 

Within the scope of the new European chemicals policy (REACH system) a new attempt is now being made to reduce the information and assessment deficit with regard to the hazardous properties and risks originating from existing chemicals. 

According to the Technical Guidance Document (TGD) for risk assessment of new and existing chemical substances (EC 2003), smdies conducted with human volunteers are strongly discouraged as they are problematic from an ethical point of view and results from such smdies should be used only in justified cases (e.g., tests which were conducted for the authorization of a medical product or when effects in already available human volunteer smdies with existing substances have been observed to be more severe than deduced from prior animal testing). However, the potential differences in sensitivity of human smdies and smdies in animals should be taken into account in the risk assessment, on a case-by-case basis. 

A threshold also exists for quantal dose responses as well as graded, i.e., there will be a dose below which no individuals respond. However, the concept of a threshold also has to be considered in relation to the variation in sensitivity in the population, especially a human population with great variability. Thus, although there will be a dose at which the greatest number of individuals show a response (see point B in Fig. 2.5), there will be those individuals who are very much more sensitive (point A in Fig. 2.5) or those who are much less sensitive (point C in Fig. 2.5). This consideration is incorporated into risk assessment of chemicals such as food additives, contaminants, and industrial chemicals (see below). 

SimpleBox was created as a research tool in environmental risk assessment. Simple-Box (Brandes et al. 1996) is implemented in the regulatory European Union System for the Evaluation of Substances (EUSES) models (Vermeire et al. 1997) that are used for risk assessment of new and existing chemicals. Dedicated SimpleBox 1.0 applications have been used for integrating environmental quality criteria for air, water, and soil in The Netherlands. Spreadsheet versions of SimpleBox 2.0 are used for multi-media chemical fate modeling by scientists at universities and research institutes in various countries. SimpleBox models exposure concentrations in the environmental media. In addition to exposure concentrations, SimpleBox provides output at the level of toxic pressure on ecosystems by calculating potentially affected fractions (PAF) on the basis of species sensitivity distribution (SSD) calculus (see Chapter 4). 

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