{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T02:48:54Z","timestamp":1780541334365,"version":"3.54.1"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T00:00:00Z","timestamp":1566000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>Arylboronic acids and esters (referred to collectively as arylboronic compounds) are commonly used intermediates in the synthesis of pharmaceuticals but pose a challenge for chemical syntheses because they are often positive for bacterial mutagenicity <jats:italic>in vitro<\/jats:italic>. As such, arylboronic compounds are then typically controlled to levels that are acceptable for mutagenic impurities, that is, the threshold of toxicological concern (TTC). This study used ICH M7 guidance to design and conduct a testing strategy to investigate the <jats:italic>in vivo<\/jats:italic> relevance of the <jats:italic>in vitro<\/jats:italic> positive findings of arylboronic compounds. Eight arylboronic compounds representing a variety of chemical scaffolds were tested in Sprague Dawley and\/or Wistar rats in the <jats:italic>in vivo Pig\u2010a<\/jats:italic> (peripheral blood reticulocytes and mature red blood cells) and\/or comet assays (duodenum and\/or liver). Five of the eight compounds were also tested in the micronucleus (peripheral blood) assay. The arylboronic compounds tested orally demonstrated high systemic exposure; thus the blood and bone marrow were adequately exposed to test article. One compound was administered intravenously due to formulation stability issues. This investigation showed that arylboronic compounds that were mutagenic <jats:italic>in vitro<\/jats:italic> were not found to be mutagenic in the corresponding <jats:italic>in vivo<\/jats:italic> assays. Therefore, arylboronic compounds similar to the scaffolds tested in this article may be considered non\u2010mutagenic and managed in accordance with the ICH Q3A\/Q3B guidelines. Environ. Mol. Mutagen. 2019. \u00a9 2019 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.22320","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T16:41:16Z","timestamp":1563900076000},"page":"766-777","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<i>In Vivo<\/i> Mutagenicity Testing of Arylboronic Acids and Esters"],"prefix":"10.1002","volume":"60","author":[{"given":"Melisa J.","family":"Masuda\u2010Herrera","sequence":"first","affiliation":[{"name":"Gilead Sciences  Foster City California 94404"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista L.","family":"Dobo","sequence":"additional","affiliation":[{"name":"Pfizer Global Research &amp; Development  Groton Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle O.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Pfizer Global Research &amp; Development  Groton Connecticut 06340"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia D.","family":"Kenny","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Hertfordshire SG12 0DP United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Galloway","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. 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West Point Pennsylvania 19486"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Jolly","sequence":"additional","affiliation":[{"name":"Toxicology Division, Eli Lilly and Company  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Trejo\u2010Martin","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California 94404"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caren","family":"Brown","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Mckeon","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Young","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Bruce","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamala","family":"Pant","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparajita","family":"Dutta","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"MilliporeSigma BioReliance\u00ae Toxicology Services  Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel P.","family":"Bercu","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California 94404"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,17]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"CallanJGA LadA StannardL HoweJ KennyJ.2013.Mutagenicity of Aryl Boronic Acids in the Mouse Lymphoma Assay. 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Available at:https:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Quality\/Q3A_R2\/Step4\/Q3A_R2__Guideline.pdf. Accessed October 25 2006."},{"key":"e_1_2_6_10_1","volume-title":"ICH Harmonised Guideline. 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