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

Kunihiko Yamashita, Shinsuke Shinoda, Saori Hagiwara, Hiroshi Miyazaki, Hiroshi Itagaki

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)843-853
    Number of pages11
    JournalJournal of Toxicological Sciences
    Volume40
    Issue number6
    DOIs
    StatePublished - 2015 Nov 10

    Fingerprint

    Local Lymph Node Assay
    Unsaturated Fatty Acids
    Peptides
    Skin
    Acids
    Squalene
    alpha-Linolenic Acid
    Guinea Pigs
    Carbon
    Succinic Acid
    Skin Tests
    Lipids
    Organisation for Economic Co-Operation and Development

    Keywords

    • Fatty acid
    • LLNA:DAE
    • Skin

    ASJC Scopus subject areas

    • Toxicology

    Cite this

    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. / Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi.

    In: Journal of Toxicological Sciences, Vol. 40, No. 6, 10.11.2015, p. 843-853.

    Research output: Contribution to journalArticle

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Miyazaki, Hiroshi; Itagaki, Hiroshi / 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.

    In: Journal of Toxicological Sciences, Vol. 40, No. 6, 10.11.2015, p. 843-853.

    Research output: Contribution to journalArticle

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