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Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non\u2010cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL\u20102H3), and in this study, we replicate this finding in human mast cells (HMC\u20101.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL\u20102H3 cells in glucose\u2010free, galactose\u2010containing media (95% confidence interval EC<jats:sub>50<\/jats:sub> = 7.5\u20139.7\u2009\u00b5<jats:sc>m<\/jats:sc>), without causing cytotoxicity. Using these same glucose\u2010free conditions, 15\u2009\u00b5<jats:sc>m<\/jats:sc> TCS dampens RBL\u20102H3 degranulation by 40%. The same ATP disruption was found with human HMC\u20101.2 cells (EC<jats:sub>50<\/jats:sub> 4.2\u201313.7\u2009\u00b5<jats:sc>m<\/jats:sc>), NIH\u20103\u2009T3 mouse fibroblasts (EC<jats:sub>50<\/jats:sub> 4.8\u20137.4\u2009\u00b5<jats:sc>m<\/jats:sc>) and primary human keratinocytes (EC<jats:sub>50<\/jats:sub> 3.0\u20134.1\u2009\u00b5<jats:sc>m<\/jats:sc>) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL\u20102H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3\u2010chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS\u2010methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non\u2010cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5\u2009\u00b5<jats:sc>m<\/jats:sc> TCS inhibits thapsigargin\u2010stimulated degranulation of RBL\u20102H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3209","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T23:05:14Z","timestamp":1437692714000},"page":"777-789","source":"Crossref","is-referenced-by-count":93,"title":["Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes"],"prefix":"10.1002","volume":"36","author":[{"given":"Lisa M.","family":"Weatherly","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical Science and Engineering  Orono ME USA"},{"name":"Department of Molecular and Biomedical Sciences University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juyoung","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina N.","family":"Hashmi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel H.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Science and Engineering  Orono ME USA"},{"name":"Department of Molecular and Biomedical Sciences University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel T.","family":"Hess","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Science and Engineering  Orono ME USA"},{"name":"Department of Physics and Astronomy University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Gosse","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Science and Engineering  Orono ME USA"},{"name":"Department of Molecular and Biomedical Sciences University of Maine  Orono ME USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2006.08.007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1408642"},{"key":"e_1_2_7_4_1","first-page":"148","article-title":"Clinical evidence for the lack of triclosan accumulation from daily use in dentifrices","volume":"13","author":"Bagley DM","year":"2000","journal-title":"Am. 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