{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:02:22Z","timestamp":1777046542530,"version":"3.51.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry, Labor and Welfare, Japan","award":["22KA2001"],"award-info":[{"award-number":["22KA2001"]}]},{"name":"Ministry, Labor and Welfare, Japan","award":["21KA1008"],"award-info":[{"award-number":["21KA1008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In March 2024, a food poisoning incident in Japan was traced to red yeast rice (beni-koji) supplements contaminated with puberulic acid (PA), a mycotoxin produced by Penicillium adametzioides. Although PA was implicated in renal dysfunction in both humans and rats, its mutagenic potential had not been clarified. Here, we comprehensively assessed the mutagenicity of PA using a tiered approach that combined in silico, in vitro, and in vivo methods. In silico quantitative structure\u2013activity relationship analyses predicted PA to be mutagenic, and in vitro Ames tests confirmed the positive finding. In contrast, in vivo assays, including the transgenic rodent gene mutation assay in mice and the Pig-a assay in rats, demonstrated no induction of mutations in kidney, glandular stomach, and blood cells, even at high exposure levels. Collectively, these findings indicate that PA is mutagenic in vitro bacterial tests, but not in mammalian in vivo systems, suggesting that the overall concern for mutagenicity in humans is low.<\/jats:p>","DOI":"10.1093\/mutage\/geag005","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:48:51Z","timestamp":1770209331000},"page":"110-118","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of mutagenic potential of puberulic acid contaminated in red yeast rice (beni-koji) health food supplements"],"prefix":"10.1093","volume":"41","author":[{"given":"Kei-ichi","family":"Sugiyama","sequence":"first","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Furuhama","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsuyoshi","family":"Horibata","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1267-3777","authenticated-orcid":false,"given":"Masataka","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Izawa","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genichiro","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Division of Organic Chemistry, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Demizu","sequence":"additional","affiliation":[{"name":"Division of Organic Chemistry, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-0367","authenticated-orcid":false,"given":"Kohei","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Division of Pathology, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Pathology, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiro","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of General Affairs, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masamitsu","family":"Honma","sequence":"additional","affiliation":[{"name":"Division of Genome Safety Science, Center for Biological Safety and Research, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]},{"name":"Division of General Affairs, National Institute of Health Sciences , 3-25-26 Tonomachi, Kawasaki, Kanagawa 210-9501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"2026042410512315100_ref1","volume-title":"Information on Adverse Events Associated with Beni-Koji (Red Yeast Rice) Related Products"},{"key":"2026042410512315100_ref2","first-page":"28","volume-title":"A Focus on Food Supplements and Functional Foods. Case Study 4: Potential Presence of Puberulic Acid in Red Yeast Rice Food Supplements in Japan","author":"FOOD SAFETY in personalized nutrition","year":"2025"},{"key":"2026042410512315100_ref3","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1053\/j.ajkd.2024.08.007","article-title":"Three cases of red yeast Rice-containing supplement-induced acute kidney injury and Fanconi syndrome","volume":"85","author":"Chikasue","year":"2025","journal-title":"Am J Kidney Dis"},{"key":"2026042410512315100_ref4","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1186\/s12882-024-03903-5","article-title":"Fanconi syndrome with acute proximal tubular injury induced by a dietary supplement containing Beni-koji: a case series report","volume":"25","author":"Habuka","year":"2024","journal-title":"BMC Nephrol"},{"key":"2026042410512315100_ref5","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.1016\/j.ekir.2024.06.022","article-title":"Certain red yeast Rice supplements in Japan cause acute Tubulointerstitial injury","volume":"9","author":"Murata","year":"2024","journal-title":"Kidney Int Rep"},{"key":"2026042410512315100_ref6","doi-asserted-by":"publisher","first-page":"302","DOI":"10.2183\/pjab.101.017","article-title":"Mechanism of puberulic acid contamination in red yeast rice tablets that caused a serious food poisoning outbreak in Japan","volume":"101","author":"Yoshinari","year":"2025","journal-title":"Proc Jpn Acad Ser B Phys Biol Sci"},{"key":"2026042410512315100_ref7","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/ja.2010.124","article-title":"In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A-C, produced by Penicillium sp. FKI-4410","volume":"64","author":"Iwatsuki","year":"2011","journal-title":"J Antibiot (Tokyo)"},{"key":"2026042410512315100_ref8","doi-asserted-by":"publisher","first-page":"7259","DOI":"10.1038\/s41598-017-07718-3","article-title":"Antimalarial troponoids, puberulic acid and viticolins; divergent synthesis and structure-activity relationship studies","volume":"7","author":"Sennari","year":"2017","journal-title":"Sci Rep"},{"key":"2026042410512315100_ref9","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1293\/tox.2025-0057","article-title":"A 28-day subacute toxicity study of puberulic acid in Crl:CD(SD) rats","volume":"38","author":"Matsushita","year":"2025","journal-title":"J Toxocol Pathol"},{"key":"2026042410512315100_ref10","doi-asserted-by":"publisher","first-page":"503388","DOI":"10.1016\/j.mrgentox.2021.503388","article-title":"Genotoxicity test battery - an assessment of its utility in early drug 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