EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity

Information on acute systemic toxicity represents a standard requirement within several pieces of chemicals legislation in the EU. One of the main drivers of conducting the test is classification and labelling. Currently, only in vivo tests are accepted by regulatory bodies and most of the standard tests use lethality as endpoint. Based on an assessment of the regulatory needs and the scientific state-of-the art in the area, EURL ECVAM considers that efforts should be directed towards a) the reduction and replacement of animal tests for the identification and classification of acute systemic toxicity, and b) the refinement of in vivo studies. Consideration should be given to collecting, organising and applying mechanistic knowledge related to this endpoint, to provide a strong mechanistic basis for the design and validation of integrated prediction models. EURL ECVAM proposes to evaluate promising components of integrated approaches for testing and assessment (IATA), including the better use of existing alternative methods, such as mechanistically relevant in vitro assays. Information on repeated dose toxicity might also be useful in supporting classification and labelling for acute systemic toxicity. One clear target is minimising animal use for satisfying information requirements for acute systemic toxicity in relation to the 2018 REACH registration deadline. The aims and objectives underpinning the EURL ECVAM strategy can only be achieved through the coordinated and concerted efforts of all stakeholders