Ingrid Gerner

Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation

During the past 20xa0years the EU legislation for the notification of chemicals has focussed on new chemicals and at the same time failed to cover the evaluation of existing chemicals in Europe. Therefore, in a new EU chemicals policy (REACH, Registration, Evaluation and Authorisation of Chemicals) the European Commission proposes to evaluate 30,000 chemicals within a period of 15xa0years. We are providing estimates of the testing requirements based on our personal experiences during the past 20xa0years. A realistic scenario based on an in-depth discussion of potential toxicological developments and an optimised “tailor-made” testing strategy shows that to meet the goals of the REACH policy, animal numbers may be significantly reduced below 10xa0million if industry would use in-house data from toxicity testing, which are confidential, if non-animal tests would be used, and if information from quantitative structure activity relationships (QSARs) would be applied in substance-tailored testing schemes. The procedures for evaluating the reproductive toxicity of chemicals have the strongest impact on the total number of animals bred for testing under REACH. We are assuming both an active collaboration with our colleagues in industry and substantial funding of the development and validation of advanced non-animal methods by the EU Commission, specifically in reproductive and developmental toxicity.

The ECVAM International Validation Study on In Vitro Tests for Skin Corrosivity. 1. Selection and Distribution of the Test Chemicals.

An international validation study on in vitro tests for skin corrosivity was conducted during 1996 and 1997 under the auspices of the European Centre for the Validation of Alternative Methods (ECVAM). The main objectives of the study were to assess the performances of selected in vitro tests in discriminating between: (a) corrosives (C) and non-corrosives (NC), for selected groups of chemicals (e.g. organic acids, phenols) and/or for all chemicals (single chemical entities only); and (b) known R35 (UN packing group I) and R34 (UN packing groups II & III) chemicals. Each test was evaluated for reliability and relevance by using a test set of 60 coded chemicals. In this paper, the test chemicals used in the validation study are identified; they include organic acids (6C/5NC), organic bases (7C/3NC), neutral organics (9NC), phenols (2C/3NC), inorganic acids (6C/1NC), inorganic bases (2C/2NC), inorganic salts (1C/2NC), electrophiles (3C/5NC) and soaps/surfactants (3NC). The in vivo classifications and important physicochemical properties (e.g. logP, pKa) of the test chemicals are given. The main criterion for including chemicals in the test set was that their corrosivity classifications were based on unequivocal animal data. Where available, structure-activity information was also used to support the corrosivity classifications. Despite the small numbers of chemicals in some of the categories, it was felt that the test set chosen represented the best possible for evaluating the performances of the in vitro tests for predicting skin corrosivity, given the limited availability of unequivocal animal data. The prediction of skin corrosivity from pH data was also investigated for those chemicals with extreme pH values (i.e. pH2 or 11.5). Nine of the 12 strongly acidic or alkaline chemicals in the test set, which were predicted to be C on the basis of their pH values, had also been found to be C in vivo.

Introduction of in vitro data into local irritation/corrosion testing strategies by means of SAR considerations: assessment of chemicals

The European legislation on control and evaluation of chemicals requires hazard and risk assessment of chemicals for human health and the environment. Technical guidance on carrying out this assessment includes the use of information based on results of testing with animals and on results of alternatives to animal testing. Within regulatory risk assessment the use of in vitro data for hazard and risk classification purposes is in the very beginning, because in vitro results do not mirror the total of effects observed in standardised animal tests, and hence cannot be easily related to current regulatory classification criteria. In vitro tests aim at the detection of only a few aspects considered crucial for the formation of a very complex health hazard observed in vivo. Therefore, they need a clear definition of the toxicological questions they can answer and of the limits of their evidence with respect to meeting regulatory classification criteria. In order to enhance the use of in vitro results within the regulatory classification procedure, the Organisation for Economic Co-operation and Development (OECD) developed tiered testing and assessment strategies that combine in vitro results and structure-activity relationship (SAR) considerations.