Title: The ECVAM International Validation Study on In Vitro Tests for Acute Skin Irritation: Selection of Test Chemicals
Publisher: FRAME
Publication Year: 2007
JRC Publication N°: JRC41184
ISSN: 0261-1929
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC41184
Type: Articles in Journals
Abstract: The ECVAM-funded skin irritation validation study (SIVS) was initiated in 2003 with the aim to evaluate whether the EpiDermTM, EPISKINTM and the SIFT alternative methods were able to reliably identify skin irritant and non-irritant chemicals and as such to replace the rabbit Draize test for skin irritation. The primary goal of the study was to evaluate the predictive capacity of the assays with regard to the EU classification system using the risk phrase R38 for skin irritants and no classification for non irritants. A secondary objective was the retrospective analysis of the data to assess whether the in vitro tests would be able to discriminate between strong (category 2), mild (category 3) and non-irritants (no category), as defined by the OECD and United Nations proposal for a Globally Harmonised System (GHS) for classification and labelling of dermal irritancy. A Chemicals Selection Sub-Committee (CSSC) was appointed to identify test chemicals to be used in the SIVS having high quality existing in vivo data with which to correlate the in vitro measurements. Since chemicals from the European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) database of reference chemicals for skin irritation / skin corrosion had been extensively used in preceding studies, the CSSC made use of novel sources for potential test chemicals. The first source of chemicals screened was the New Chemicals Database (NCD) which is the central archive within the EU notification scheme for 'new' commercial chemicals. Data registered in NCD originate from standard assays, submitted in compliance with the legislation regulating marketing of industrial chemicals, and are subject to quality assurance by EU member state competent authorities. In addition, to obtain 'existing' chemicals readily available from major manufacturing and/or distribution sources, additional databases were surveyed such as the Toxic Substance Control Act (TSCA) database maintained by the US Environmental Protection Agency (EPA) and the ECETOC database with the exclusion of those chemicals used in the previous optimisation and prevalidation phases. A total of approximately 3500 chemicals from the NCD and 1600 from the additional databases were screened by the CSSC. Pre-determined selection criteria were applied to ensure primarily the quality of the in vivo data and the practicability of testing. Nevertheless, the number of chemicals fulfilling the CSSC selection criteria was found to be limited, particularly when identifying GHS category 2 chemicals. However, a total set of 60 chemicals were selected and proposed to be tested in the SIVS. The selected chemicals (1) represented statistically justified sample sizes for distinguishing R38 from non classified chemicals, (2) provided a balanced representation of the three GHS categories to allow for post-hoc evaluation of the performance of the assays for that classification system, and (3) acknowledged to a certain degree the large prevalence known to exist for chemicals which have oedema and erythema scores of 0. These chemicals were independently coded and distributed to the participating laboratories. The selected chemicals presented a variety of molecular structures, functional chemical groups, effect and use categories, as well as a wide range of physical-chemical properties. They represented a challenging set of chemicals relevant to current industrial commerce for the alternative methods being validated.
JRC Institute:Institute for Health and Consumer Protection

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