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Tonnage-based information requirements are specified in the proposal on the regulation on the Registration, Evaluation and Authorisation of Chemicals (REACH) in the European Union. The hazard assessment for toxic endpoints should be performed by using a tiered approach, i.e. as an information strategy (IS), starting with an evaluation of all of the data already available, including animal in vivoand in vitrodata, and human evidence and case reports, as well as data from (Quantitative)-Structure Activity Relationships ([Q]SARs) or read-across, before any further testing is suggested. To contribute to the implementation of the REACH system, the Nordic countries launched two projects: 1) a review of currently used testing strategies, including a comparison with the REACH requirements; and 2) the development of detailed ISs for skin and eye irritation/corrosion. The review showed that the ISs and classification criteria for the selected endpoints are inconsistent in many cases. In the classification criteria, human data and in vivotest results are usually the prerequisites. Other types of information, such as data from in vitrostudies, can sometimes be used, but usually as supportive evidence only. This differs from the REACH ISs, where QSARs, read-across and in vitrotesting are important elements. In the other part of the project, an IS for skin and eye irritation/corrosion was proposed. The strategy was “tested” by using four high production volume (HPV) chemicals: hydrogen peroxide, methyl tertiary-butyl ether (MTBE), trivalent chromium, and diantimony trioxide, but only MTBE and trivalent chromium are dealt with in this paper. The “test” revealed that in vivodata, human case reports and physical-chemical data were available and could be used in the evaluation. Classification could be based on the proposed IS and the existing data in all cases, except for the eye irritation/corrosion of trivalent chromium. Weight-of-evidence analysis appeared to be a useful step in the ISs proposed, and including it in the REACH strategies should be considered. For these chemicals, few in vitroand (Q)SAR data were available — more of these data would be generated, if the relevant guidance and legislation on classification were updated.

According to the new chemicals policy of the European Union (EU), most chemicals, i.e. the 20,000 chemicals manufactured or imported at 1–10 tons annually, should be tested primarily by using in vitromethods. Also, for other chemicals, the use of in vitromethods is encouraged in the testing strategies given in the draft EU legislation. However, the validation and international acceptance of in vitrotests has been slow. Only recently has the OECD approved four new in vitrotest methods, validated by the European Centre for the Validation of Alternative Methods. An analysis of ten randomly selected risk assessment reports of the EU Existing Chemicals Risk Assessment Programme showed that in vitrostudies, for example, on cytotoxicity to different cell cultures, cell transformation, metabolism and skin penetration (a total of 115 studies) were used for the assessments. Key metabolic pathways and mechanisms of toxicity have been elucidated, for some chemicals, by using in vitromethods. On the other hand, the results of in vitrostudies were regarded as secondary or unreliable in some cases. For several toxic endpoints, in vitromethods will probably serve as screening tools and for mechanistic studies, while target organ toxicity or physiologically regulated adverse effects caused by long-term exposure are difficult to observe without the use of animal models.