Ability of non-animal methods for skin sensitisation to detect pre- and pro-haptens: Report and recommendations of an EURL ECVAM expert meeting
Significant progress has been made in the development, validation and regulatory acceptance of in chemico and in vitro test methods for skin sensitisation. Although these methods have been shown to perform relatively well (about 80% accuracy in predicting Local Lymph Node Assay (LLNA) classifications) a concern was raised on the regulatory acceptability of negative results since it was questioned whether these methods are able to predict chemicals that need to be activated to act as sensitisers.
In order to inform ongoing discussions at the regulatory level in the EU, EURL ECVAM held an expert meeting on 10-11 November 2015 to analyse the extent to which in chemical and in vitro methods are able to correctly identify chemicals that need to be activated either through abiotic activation (pre-haptens) and/or through biotic (enzyme-mediated) mechanisms (pro-haptens) to acquire skin sensitisation potential.
The expert group analysed a list of 127 chemicals, with available LLNA and in vitro data, 22% of which were considered to be pre- and/or pro-haptens. The pre-haptens, constituting the vast majority of chemicals requiring activation, where mostly correctly identified by both the in chemico and in vitro assays whereas the pro-haptens which represent a small subset of sensitising chemicals, were generally identified correctly by one of the cell-based assays.
As a result, the expert group recommended that negative in vitro data should be accepted unless there is a compelling scientific argument that a substance is likely to be an exclusively metabolically activated pro-hapten.
CASATI Silvia;
ASCHBERGER Karin;
ASTURIOL BOFILL David;
BASKETTER David;
DIMITROV S;
DUMONT Coralie;
KARLBERG Ann-Therese;
LEPOITTEVIN Jean Pierre;
PATLEWICZ Grace;
ROBERTS David;
WORTH Andrew;
2016-02-26
Publications Office of the European Union
JRC100479
978-92-79-55333-2,
1831-9424,
EUR 27752,
OP LB-NA-27752-EN-N,
https://publications.jrc.ec.europa.eu/repository/handle/JRC100479,
10.2788/01803,
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