Further development of llna: Dae method as Stand-Alone Skin-Sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals

Kunihiko Yamashita, Shinsuke Shinoda, Saori Hagiwara, Hiroshi Itagaki

    • 1 Citations

    Abstract

    To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elici-tation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnam-ic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

    Original languageEnglish
    Pages (from-to)137-150
    Number of pages14
    JournalJournal of Toxicological Sciences
    Volume40
    Issue number2
    StatePublished - 2015

    Fingerprint

    Local Lymph Node Assay
    Ear
    Lymph Nodes
    Skin
    Dinitrochlorobenzene
    Aldehydes

    Keywords

    • Elicitation
    • LLNA
    • LLNA:DAE
    • Potency
    • Sensitization

    ASJC Scopus subject areas

    • Toxicology

    Cite this

    Further development of llna : Dae method as Stand-Alone Skin-Sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals. / Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi.

    In: Journal of Toxicological Sciences, Vol. 40, No. 2, 2015, p. 137-150.

    Research output: Contribution to journalArticle

    Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi / Further development of llna : Dae method as Stand-Alone Skin-Sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals.

    In: Journal of Toxicological Sciences, Vol. 40, No. 2, 2015, p. 137-150.

    Research output: Contribution to journalArticle

    @article{83082f8c6da64880b6f5d761513383af,
    title = "Further development of llna: Dae method as Stand-Alone Skin-Sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals",
    keywords = "Elicitation, LLNA, LLNA:DAE, Potency, Sensitization",
    author = "Kunihiko Yamashita and Shinsuke Shinoda and Saori Hagiwara and Hiroshi Itagaki",
    year = "2015",
    volume = "40",
    pages = "137--150",
    journal = "Journal of Toxicological Sciences",
    issn = "1880-3989",
    publisher = "Japanese Society of Toxicological Sciences",
    number = "2",

    }

    TY - JOUR

    T1 - Further development of llna

    T2 - Journal of Toxicological Sciences

    AU - Yamashita,Kunihiko

    AU - Shinoda,Shinsuke

    AU - Hagiwara,Saori

    AU - Itagaki,Hiroshi

    PY - 2015

    Y1 - 2015

    N2 - To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elici-tation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnam-ic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

    AB - To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elici-tation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnam-ic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

    KW - Elicitation

    KW - LLNA

    KW - LLNA:DAE

    KW - Potency

    KW - Sensitization

    UR - http://www.scopus.com/inward/record.url?scp=84924770701&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84924770701&partnerID=8YFLogxK

    M3 - Article

    VL - 40

    SP - 137

    EP - 150

    JO - Journal of Toxicological Sciences

    JF - Journal of Toxicological Sciences

    SN - 1880-3989

    IS - 2

    ER -