{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:35:49Z","timestamp":1787168149779,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for JSPS Fellows","award":["JP18J23393"],"award-info":[{"award-number":["JP18J23393"]}]},{"name":"the Ministry of Health, Labor, and Welfare, Japan","award":["21KD1004"],"award-info":[{"award-number":["21KD1004"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP18H03381"],"award-info":[{"award-number":["JP18H03381"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Propolis is a resinous mixture produced by bees from their secretions and plant material, so its composition varies depending on its botanical origin. Propolis has several beneficial bioactivities, but its skin sensitization properties have long been suspected. Nevertheless, the skin sensitization potency of Brazilian green propolis (BGP) has not been scientifically evaluated. Here, we used scientifically reliable tests to evaluate it. In vitro antigenicity test based on the human cell line activation test (OECD TG 442E) was performed by measuring the expression of CD54 and CD86, which are indicators of the antigenicity of test substances, on THP-1 and DC2.4 cells. BGP did not affect the expression of either marker on THP-1 cells, but upregulated the expression of CD86 on DC2.4 cells, suggesting that BGP may be a skin sensitizer. Then, we performed local lymph node assay (LLNA, OECD TG 429) as a definitive in vivo test. LLNA showed that 1.70% BGP primed skin sensitization and is a \u201cmoderate sensitizer\u201d. Our results indicate scientific proof of the validity of arbitrary concentrations (1\u20132%), which have been used empirically, and provide the first scientific information on the safe use of BGP.<\/jats:p>","DOI":"10.3390\/ijms222413538","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"13538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of the Skin-Sensitizing Potential of Brazilian Green Propolis"],"prefix":"10.3390","volume":"22","author":[{"given":"Erina","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"},{"name":"Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-9215","authenticated-orcid":false,"given":"Keishi","family":"Ishida","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1832-624X","authenticated-orcid":false,"given":"Daisuke","family":"Matsumaru","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ido","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani 509-0293, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhei","family":"Hiromori","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science 3500-3, Minamitamagaki, Suzuka 513-8670, Mie, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisamitsu","family":"Nagase","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"},{"name":"Faculty of Pharmaceutical Sciences, Gifu University of Medical Science, 4-3-3 Nijigaoka, Kani 509-0293, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2683-0075","authenticated-orcid":false,"given":"Tsuyoshi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Gifu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"ref_1","first-page":"308249","article-title":"Propolis: A wonder bees product and its pharmacological potentials","volume":"2013","author":"Wagh","year":"2013","journal-title":"Adv. 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