Opportunities to prevent new animal testing in the area of acute toxicity

JRC scientists have been exploring possible ways to waive mammalian acute toxicity tests, as a contribution towards international efforts aimed at fulfilling regulatory information requirements on chemical safety while at the same time reducing or avoiding the use of vertebrate animals.

Acute systemic toxicity testing is one in vivo test that always has generated and still generates a lot of debate due to scientific and ethical considerations. In view of the upcoming final registration deadline for chemicals under the EU REACH Regulation, in May 2018, and in line with the EURL ECVAM strategy to replace, reduce and refine the use of animals in the assessment of acute mammalian systemic toxicity, JRC scientists conducted a survey directed to experts in the field of toxicity testing with the ultimate aim of understanding how data from acute systemic toxicity tests are used in practice, and whether non-animal methods and/or existing in vivo data could provide the information needed. The results of the survey were complemented with a retrospective data analysis of acute and repeated-dose toxicity studies from ECHA registration dossiers. The overall outcome of these investigations (Graepel et al., 2016) supported the use of data from 28-day toxicity tests in order to identify non-classified chemicals under the EU CLP Regulation. The strength of this approach lies in the fact that non-classified chemicals make-up the majority of chemicals currently registered under REACH. In particular, JRC scientists have shown in their analysis that with the use of a previously established threshold of 200 mg/kg b.w./day (Bulgeroni et al., 2009), both NOAEL and LOAEL values can be used in order to identify non-classified chemicals. A higher threshold of 1000 mg/kg b.w./day, as proposed by ECHA in the revision of their guidance document on acute toxicity, would give greater confidence in the predictions. Importantly, the answers to the survey questionnaire showed also willingness to adopt waiving opportunities.

Further information: ec.europa.eu