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doi:10.1016/j.fct.2008.01.019 
Copyright © 2008 Elsevier Ltd All rights reserved.
Comparison of the skin sensitizing potential of unsaturated compounds as assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT)
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R. Kreilinga, H.M. Hollnagelb, 1, L. Harengb, D. Eiglerc, M.S. Leea, P. Griema, B. Dreeßend, M. Klebere, A. Albrechtf, C. Garciag and A. Wendelh, 
, 
Received 26 September 2007;
Abstract
The skin sensitization potential of eight unsaturated and one saturated lipid (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis that chemicals with unsaturated carbon–carbon double bonds may result in a higher number of unspecific (false positive) results in the LLNA compared to the GPMT. Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid, maleic acid, squalene and octinol) gave clear positive results in the LLNA (stimulation index (SI) 
3) and thus would require labelling as skin sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the GPMT, besides some sporadic skin reactions, reproducible skin reactions indicating an allergic response were found in a few animals for four test substances. Based on the GPMT results, only undecylenic acid would have to be classified and labelled as a skin sensitizer according to the European Dangerous Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive), while the other seven test substances would not require labelling. Possible mechanisms for unspecific skin cell stimulation and lymph node responses are discussed. In conclusion, the suitability of the LLNA for unsaturated compounds bearing structural similarity to the tested substances should be carefully considered and the GPMT should remain available as an accepted test method for skin sensitization hazard identification.
Keywords: Skin sensitization; False positives; OECD guidelines
Abbreviations: GPMT, guinea pig maximization test; LLNA, local lymph node assay; SI, stimulation index; LNWI, lymph node weight index
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Statistically significant increase (p < 0.01) compared to vehicle control group.Corresponding author. Tel.: +49 7531882229; fax: +49 7531883099.1 Present address: Dow Europe GmbH, CH-8810 Horgen, Switzerland.
