{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:53:34Z","timestamp":1760576014341,"version":"build-2065373602"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mitochondrial dysfunction and excessive reactive oxygen species production contributes to the pathophysiology of aging. Coenzyme Q10 is thought to protect mitochondria from oxidative damage; thus, mitoquinone was developed as mitochondria\u2010targeted analogue with similar antioxidant activity. Mitoquinone is the oxidized form of mitoquinol. Mitoquinone\/mitoquinol mesylate has been proposed as a food ingredient. As part of the safety analysis, we performed genotoxicity assays and a 39\u2010week toxicity study to determine overall toxicity potential. Mitoquinone mesylate showed no evidence of genotoxic potential in two in vitro assays, bacterial reverse mutation and human lymphocyte chromosome aberration, nor in the in vivo micronucleus test in rats. In the 39\u2010week study in dogs, there were no findings observed, which were considered to represent adverse systemic toxicity; therefore, the high dose level (40\u2009mg\/kg\/day) was considered the NOAEL. The principal findings in this study were fecal disturbances and vomiting. These findings were considered to be due to a local, possibly irritant effect of the test substance on the gastrointestinal tract and were not considered adverse as there were no impacts on clinical or histopathology. This highest dose exceeds the expected daily human intake more than 100\u2010fold. Data from well\u2010designed clinical trials actively collecting safety endpoints corroborate that 20\u2009mg\/day can be safely consumed and is not likely to result in significant gastrointestinal complaints. These results support the conclusion that the use of mitoquinone\/mitoquinol mesylate as a food ingredient is safe.<\/jats:p>","DOI":"10.1002\/jat.4654","type":"journal-article","created":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T05:24:05Z","timestamp":1718083445000},"page":"1555-1571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral subchronic toxicity study and genetic toxicity evaluation of mitoquinone mesylate"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-6283","authenticated-orcid":false,"given":"E. Siobhan","family":"Mitchell","sequence":"first","affiliation":[{"name":"MitoQ Ltd.  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawna","family":"Lemke","sequence":"additional","affiliation":[{"name":"EAS Consulting Group  Alexandria Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendon","family":"Woodhead","sequence":"additional","affiliation":[{"name":"MitoQ Ltd.  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Coleman","sequence":"additional","affiliation":[{"name":"Labcorp Early Development Laboratories Ltd.  Huntingdon UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(75)90046-1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(95)00024-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-5193(63)90004-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5173(98)00382-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.2.547"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8575263"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100308"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24377"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0032-9592(03)00258-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600964722"},{"key":"e_1_2_7_12_1","unstructured":"Environmental Protection Agency. (1998a).US EPA Health Effects Test Guidelines number OPPTS 870.5100. Bacterial reverse mutation test. EPA 712\u2010C\u201098\u2010247"},{"key":"e_1_2_7_13_1","unstructured":"Environmental Protection Agency. (1998b).Health Effects Test Guidelines number OPPTS 870.5375. In Vitro Mammalian Chromosome Aberration Test. EPA 712\u2010C\u201098\u2010223"},{"key":"e_1_2_7_14_1","unstructured":"Environmental Protection Agency. (1998c).Health Effects Test Guidelines number OPPTS 870.5395. Mammalian Erythrocyte Micronucleus Test. EPA 712\u2010C\u201098\u2010226."},{"key":"e_1_2_7_15_1","unstructured":"Food and Drug Administration. (2024).GRAS Notices. Retrieved April 15 2024 fromhttps:\/\/www.cfsanappsexternal.fda.gov\/scripts\/fdcc\/?set=GRASNotices"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.219329"},{"key":"e_1_2_7_17_1","first-page":"96","volume-title":"Statistical methods for research workers","author":"Fisher R. A.","year":"1973"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00670.2017"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.268680"},{"key":"e_1_2_7_20_1","unstructured":"International Council for Harmonisation of Technical Requirements. (1998).ICH Harmonised Tripartate Guideline S4 Duration of Chronic Toxicity Testing in Animals (Rodent and non\u2010rodent)."},{"key":"e_1_2_7_21_1","unstructured":"ISCN. (1985).An international system for human cytogenetic nomenclature. InD. G.Harnden&H. P.Klinger(Eds.).S. Karger AG."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.03.026"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020451"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/41.1-2.133"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009093200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00067.2023"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03190873"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9050386"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900347RR"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1161(83)90010-9"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp3005963"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/10.2.129"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.11.006"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/35008121"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101674"},{"key":"e_1_2_7_36_1","unstructured":"Organisation for Economic Co\u2010operation and Development. (1997a).Guideline for the Testing of Chemicals No. 471. Bacterial Reverse Mutation Test."},{"key":"e_1_2_7_37_1","unstructured":"Organisation for Economic Co\u2010operation and Development. (1997b).Guideline for the Testing of Chemicals No. 473. In Vitro Mammalian Chromosomal Aberration Test."},{"key":"e_1_2_7_38_1","unstructured":"Organisation for Economic Co\u2010operation and Development. (1997c).Guideline for the Testing of Chemicals. Genetic Toxicology: Mammalian Erythrocyte Micronucleus Test Guideline 474."},{"key":"e_1_2_7_39_1","unstructured":"Oregon State University Linus Pauling Institute. (2018).Coenzyme Q10. Available athttps:\/\/lpi.oregonstate.edu\/mic\/dietary-factors\/coenzyme-Q10"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14081748"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(00)01674-1"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.10.039"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080063"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10787"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600450R"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320720"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP272491"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103244"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0931245100"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23148"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001968"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101673"},{"volume-title":"Ullmann's encyclopedia of industrial chemistry","year":"2012","author":"Wimmer T.","key":"e_1_2_7_53_1"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467212666181127151059"}],"container-title":["Journal of Applied Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jat.4654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:41:17Z","timestamp":1760542877000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jat.4654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,11]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jat.4654"],"URL":"https:\/\/doi.org\/10.1002\/jat.4654","archive":["Portico"],"relation":{},"ISSN":["0260-437X","1099-1263"],"issn-type":[{"type":"print","value":"0260-437X"},{"type":"electronic","value":"1099-1263"}],"subject":[],"published":{"date-parts":[[2024,6,11]]},"assertion":[{"value":"2024-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}