An Overall Strategy for the Testing of Chemicals for Human Hazard and Risk Assessment under the EU REACH System

Abstract

In its White Paper, Strategy for a Future Chemicals Policy, published in 2001, the European Commission (EC) proposed the REACH (Registration, Evaluation and Authorisation of CHemicals) system to deal with both existing and new chemical substances. This system is based on a top-down approach to toxicity testing, in which the degree of toxicity information required is dictated primarily by production volume (tonnage). If testing is to be based on traditional methods, very large numbers of laboratory animals could be needed in response to the REACH system, causing ethical, scientific and logistical problems that would be incompatible with the time-schedule envisaged for testing. The EC has emphasised the need to minimise animal use, but has failed to produce a comprehensive strategy for doing so. The present document provides an overall scheme for predictive toxicity testing, whereby the non-animal methods identified and discussed in a recent and comprehensive ECVAM document, could be used in a tiered approach to provide a rapid and scientifically justified basis for the risk assessment of chemicals for their toxic effects in humans. The scheme starts with a preliminary risk assessment process (involving available information on hazard and exposure), followed by testing, based on physicochemical properties and (Q)SAR approaches. (Q)SAR analyses are used in conjunction with expert system and biokinetic modelling, and information on metabolism and identification of the principal metabolites in humans. The resulting information is then combined with production levels and patterns of use to assess potential human exposure. The nature and extent of any further testing should be based strictly on the need to fill essential information gaps in order to generate adequate risk assessments, and should rely on non-animal methods, as far as possible. The scheme also includes a feedback loop, so that new information is used to improve the predictivity of computational expert systems. Several recommendations are made, the most important of which is that the European Union (EU) should actively promote the improvement and validation of (Q)SAR models and expert systems, and computer-based methods for biokinetic modelling, since these offer the most realistic and most economical solution to the need to test large numbers of chemicals.

Biokinetic Modeling andin Vitro–in VivoExtrapolations

“…Thus, the approach relies on the availability of methods studying these toxicity pathways, making use of modern biology methods including systems biology and the "omics," in combination (integration) with modeling approaches. The relevance of this paradigm shift for the science of toxicology will be obvious, as was earlier described in a report by the Health Council of the Netherlands entitled Toxicity Testing: A More Efficient Approach (HCN, 2001) and also by Combes et al (2003). Moreover, the development of this area of research is imminent also in the light of the changes it will encompass for regulatory risk assessment procedures, including a number of recent European policy changes (cosmetics; the REACH chemicals policy), explicitly calling for a more extensive use of in vitro and other nonanimal methods.…”

Radiological/Nuclear Decontamination – Reduce the Risk

“…But, due to low biodegradability and its ability to mobilize heavy metal ions into the environment, its use and the release to the environment in larger quantities is restricted today and alternatives had to be found [21]. Another strong chelating agent for a wide spectrum of cations is citric acid.…”

Regulatory and Nonregulatory Strategies for Improving Children's Environmental Health in Canada

“…Manufacturers and importers will be required to gather information on the properties of their substances, which will help them manage them safely, and to register the information in a central database. A chemicals agency will act as the central point in the REACH system: It will run the databases necessary to operate the system, coordinate the in-depth evaluation of suspicious chemicals, and operate a public database so that consumers and professionals can find hazard information (Combes et al, 2006a(Combes et al, , 2006b.…”