title: 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.
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.
authors.affiliation: Corporate Research Center, Daicel Corporation.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yamashita
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shinoda
authors.forename: Saori
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itagaki
mesh_terms: D000818:Animals; D005189:False Positive Reactions; D005231:Fatty Acids, Unsaturated / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D023441:Local Lymph Node Assay; D051379:Mice; D008808:Mice, Inbred CBA; D012867:Skin / Q000276:immunology*; D012882:Skin Tests / Q000379:methods
chemical_list: D005231:Fatty Acids, Unsaturated