{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:43:14Z","timestamp":1792906994613,"version":"4.5.0"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methyl acrylate (MA) and ethyl acrylate (EA) had previously tested positive for mutagenicity in vitro, but in vivo studies were negative. One of the metabolism pathways of alkyl acrylates is conjugation with glutathione. The glutathione availability is restricted in standard in vitro test systems so that they do not reflect the in vivo metabolism in this respect. We investigated whether the addition of glutathione to the in vitro L5178Y\/TK<jats:sup>+\/\u2212<\/jats:sup> mouse lymphoma mutagenicity test prevents alkyl acrylate\u2019s mutagenicity in vitro. We also investigated whether the quantitative relationships support the notion that the GSH supplemented in vitro systems reflect the true in vivo activity. Indeed, glutathione concentrations as low as 1\u00a0mM completely negate the mutagenicity of MA and EA in the L5178Y\/TK<jats:sup>+\/\u2212<\/jats:sup> mouse lymphoma mutagenicity test up to the highest concentrations of the two acrylates tested, 35\u00a0\u00b5g\/ml, a higher concentration than that previously found to be mutagenic in this test (14\u00a0\u00b5g MA\/ml and 20\u00a0\u00b5g EA\/ml). 1\u00a0mM Glutathione reduced the residual MA and EA at the end of the exposure period in the mutagenicity tests by 96\u201397%, but in vivo up to 100\u00a0mg\/kg body weight MA and EA left the glutathione levels in the mouse liver and forestomach completely intact. It is concluded that the in-situ levels of glutathione, 7.55\u2009\u00b1\u20090.57 and 2.84\u2009\u00b1\u20090.22\u00a0\u00b5mol\/g mouse liver and forestomach, respectively, can efficiently protect against MA and EA-induced mutagenicity up to the high concentration of 100\u00a0mg MA and EA\/kg body weight and that the negative in vivo mutagenicity tests on MA and EA reflect the true in vivo situation.\n<\/jats:p>","DOI":"10.1007\/s00204-022-03322-1","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T08:02:56Z","timestamp":1655280176000},"page":"2573-2587","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genotoxicity of methyl acrylate and ethyl acrylate and its relationship with glutathione"],"prefix":"10.1007","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7607-1329","authenticated-orcid":false,"given":"F.","family":"Oesch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Honarvar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Fabian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Finch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Hindle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Wiench","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Landsiedel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"3322_CR1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1093\/mutage\/4.4.283","volume":"4","author":"J Ashby","year":"1989","unstructured":"Ashby J et al (1989) Inactivity of ethyl acrylate in the mouse bone marrow micronucleus assay. 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Ames test and mouse bone marrow micronucleus test on acrylic resin monomer and other additives. Nippon Koshu Liisei Zasshi 29:236\u2013239","journal-title":"Nippon Koshu Liisei Zasshi"},{"key":"3322_CR5","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.mrgentox.2005.01.005","volume":"582","author":"Z Kirpnick","year":"2005","unstructured":"Kirpnick Z et al (2005) Yeast DliL assay detects clastogens. Mutat Res 582:116\u2013134","journal-title":"Mutat Res"},{"key":"3322_CR6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S1383-5718(97)00115-0","volume":"394","author":"AD Mitchell","year":"1997","unstructured":"Mitchell AD, Auletta AE, Clive D, Kirby PE, Moore MM, Myhr BC (1997) The L5178Y\/TK+\/\u2212 mouse lymphoma specific gene and chromosomal mutation assay. A phase III report of the U.S. Environmental Protection Agency Gene-Tox Program. 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