ECVAMs ongoing activities in the area of acute oral toxicity related to the 2009 deadline set by the Seventh Amendment to the Cosmetics Directive (76/768/EEC)

The 7th Amendment of the Cosmetics Directive (76/768/EEC) set up clear timelines for banning the animal testing and marketing of cosmetic products and their ingredients tested on animals. For most of the human health effects, including acute toxicity, the deadline is March 2009. Therefore, the European Centre for the Validation of Alternative Methods (ECVAM) is recently putting considerable effort into developing and validating alternative methods in the area of acute toxicity. The large Integrated Project ACuteTox, funded by the European Commission¿s 6th Framework Programme, started in 2005 with the aim of developing and pre-validating a testing strategy to fully replace acute oral toxicity testing in vivo. As a follow-up to the international validation study on the prediction of acute toxicity by cytotoxicity assays and taking into consideration the high prevalence of non-toxic substances in the New Chemicals Database (87% with LD50 > 2000 mg/kg) ECVAM has commissioned a validation study in which 56 industrial chemicals (of which 60% cosmetic ingredients) are tested to assess the predictive capacity of the validated 3T3/Neutral Red Uptake (NRU) cytotoxicity assay to discriminate between toxic/hazardous (LD50 2000 mg/kg) substances. The validated protocol of the test was established on the robotic testing facility at the Institute for Health and Consumer Protection and this automated version is under evaluation using the same set of chemicals. A third laboratory in the US is assessing an abbreviated version of the validated 3T3/NRU protocol, which is less costly and more industry-friendly. Despite all these efforts, it is unlikely that validated and regulatory accepted alternative methods and/or strategies for acute toxicity will be available in March 2009. Thus, following the initiatives undertaken by the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, ECVAM proposed an approach to identify non-toxic compounds (LD50 > 2000 mg/kg) using information from 28-days repeated dose toxicity studies. A Non Observed Adverse Effect Level threshold was set that allowed the correct identification of 63% of non-toxic compounds, while only less then 1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.JRC.DDG.I.3-In-vitro method