PMID- 26558466 OWN - NLM STAT- MEDLINE DCOM- 20160822 LR - 20151112 IS - 1880-3989 (Electronic) IS - 0388-1350 (Linking) VI - 40 IP - 6 DP - 2015 Dec TI - Unsaturated fatty acids show clear elicitation responses in a modified local lymph node assay with an elicitation phase, and test positive in the direct peptide reactivity assay. PG - 843-53 LID - 10.2131/jts.40.843 [doi] AB - The Organisation for Economic Co-operation and Development (OECD) Test Guidelines (TG) adopted the murine local lymph node assay (LLNA) and guinea pig maximization test (GPMT) as stand-alone skin sensitization test methods. However, unsaturated carbon-carbon double-bond and/or lipid acids afforded false-positive results more frequently in the LLNA compared to those in the GPMT and/or in human subjects. In the current study, oleic, linoleic, linolenic, undecylenic, fumaric, maleic, and succinic acid and squalene were tested in a modified LLNA with an elicitation phase (LLNA:DAE), and in a direct peptide reactivity assay (DPRA) to evaluate their skin-sensitizing potential. Oleic, linoleic, linolenic, undecylenic and maleic acid were positive in the LLNA:DAE, of which three, linoleic, linolenic, and maleic acid were positive in the DPRA. Furthermore, the results of the cross-sensitizing tests using four LLNA:DAE-positive chemicals were negative, indicating a chemical-specific elicitation response. In a previous report, the estimated concentration needed to produce a stimulation index of 3 (EC3) of linolenic acid, squalene, and maleic acid in the LLNA was < 10%. Therefore, these chemicals were classified as moderate skin sensitizers in the LLNA. However, the skin-sensitizing potential of all LLNA:DAE-positive chemicals was estimated as weak. These results suggested that oleic, linoleic, linolenic, undecylenic, and maleic acid had skin-sensitizing potential, and that the LLNA overestimated the skin-sensitizing potential compared to that estimated by the LLNA:DAE. FAU - Yamashita, Kunihiko AU - Yamashita K AD - Corporate Research Center, Daicel Corporation. FAU - Shinoda, Shinsuke AU - Shinoda S FAU - Hagiwara, Saori AU - Hagiwara S FAU - Miyazaki, Hiroshi AU - Miyazaki H FAU - Itagaki, Hiroshi AU - Itagaki H LA - eng PT - Journal Article PL - Japan TA - J Toxicol Sci JT - The Journal of toxicological sciences JID - 7805798 RN - 0 (Fatty Acids, Unsaturated) SB - IM MH - Animals MH - False Positive Reactions MH - Fatty Acids, Unsaturated/*immunology MH - Female MH - Guinea Pigs MH - Humans MH - *Local Lymph Node Assay MH - Mice MH - Mice, Inbred CBA MH - Skin/*immunology MH - Skin Tests/methods EDAT- 2015/11/13 06:00 MHDA- 2016/08/23 06:00 CRDT- 2015/11/13 06:00 PHST- 2015/11/13 06:00 [entrez] PHST- 2015/11/13 06:00 [pubmed] PHST- 2016/08/23 06:00 [medline] AID - 10.2131/jts.40.843 [doi] PST - ppublish SO - J Toxicol Sci. 2015 Dec;40(6):843-53. doi: 10.2131/jts.40.843.