{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:53:37Z","timestamp":1768913617592,"version":"3.49.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Tetramethylammonium hydroxide (TMAH) is a quaternary ammonium compound that is both a base corrosive and a cholinergic agonist, and it is widely used in the photoelectric and semiconductor industries. It causes corrosive skin injuries and systemic cholinergic toxicity with death primarily resulting from respiratory failure without efficacious early decontamination.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective observational study was performed of all cases of TMAH exposure reported to the Taiwan Poison Control Center between July 2010 and October 2017. Retrieved medical records were independently reviewed by two trained clinical toxicologists.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Despite immediate (&lt;\u20095\u2009min) skin decontamination with copious amounts of tap water, one patient exposed to 25% TMAH involving \u22655% of total body surface area (TBSA) developed significant systemic toxicity. Patients exposed to 25% TMAH involving \u22641% TBSA developed first-degree chemical skin injuries but no systemic toxicity. Among patients exposed to lower concentrations (\u22642.38%) of TMAH, the majority only experienced first-degree chemical skin injuries without systemic signs. Patients exposed to 0.5% TMAH involving nearly their entire TBSA developed no chemical skin injuries or systemic toxicity. All patients who had only first-degree chemical skin injuries did not develop systemic toxicity after exposure to either 2.38% or 25% TMAH.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>TMAH acts as an alkaline corrosive and cholinergic agonist. Systemic signs attributable to TMA<jats:sup>+<\/jats:sup> can rapidly lead to respiratory failure and death after dermal exposure. We have demonstrated that an amphoteric solution may be efficacious for skin decontamination on-site immediately to prevent or ameliorate such toxicity. This practice especially carries a valuable potential in managing victims (patients) who have been exposed to those chemicals with immediate life-threatening toxicity (e.g. TMAH), suggesting that its early utilization deserves further study.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s40360-020-00465-8","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T17:05:20Z","timestamp":1606755920000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Presentations of tetramethylammonium hydroxide dermal exposure and the valuable potential of diphoterine solution in decontamination: a retrospective observational study"],"prefix":"10.1186","volume":"21","author":[{"given":"Chih-Kang","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan H.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Ling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Chang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Zong","family":"Hung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Chiao","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jou-Fang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"465_CR1","first-page":"113","volume":"78","author":"D Ackermann","year":"1923","unstructured":"Ackermann D, Holtz F, Reinwein H. Reindarstellung und konstitutionsemitteelung der tetramins, eines giftes aus Aktina equina. Z Biol. 1923;78:113.","journal-title":"Z Biol"},{"key":"465_CR2","unstructured":"United States Environmental Protection Agency. http:\/\/www.epa.gov\/cdr\/tools\/data\/2002-vol.html, Accessed 07 Nov 2019."},{"key":"465_CR3","unstructured":"United States Environmental Protection Agency. http:\/\/java.epa.gov\/opptchemicalsearch\/1, Accessed 07 Nov 2019."},{"issue":"14","key":"465_CR4","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.3390\/su11143923","volume":"11","author":"VI Francesco Ferella","year":"2019","unstructured":"Francesco Ferella VI, Zueva S, Corradini V, Ippolito NM, Birloaga IP, Michelis I, et al. Aerobic treatment ofWaste process solutions from the semiconductor industry: from lab to pilot scale. Sustainability. 2019;11(14):3923.","journal-title":"Sustainability"},{"issue":"1","key":"465_CR5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.resuscitation.2011.07.006","volume":"83","author":"CL Wu","year":"2012","unstructured":"Wu CL, Su SB, Chen JL, Chang CP, Guo HR. Tetramethylammonium ion causes respiratory failure related mortality in a rat model. Resuscitation. 2012;83(1):119\u201324.","journal-title":"Resuscitation."},{"issue":"2","key":"465_CR6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1539\/joh.X7001","volume":"50","author":"CL Wu","year":"2008","unstructured":"Wu CL, Su SB, Chen JL, Lin HJ, Guo HR. Mortality from dermal exposure to tetramethylammonium hydroxide. J Occup Health. 2008;50(2):99\u2013102.","journal-title":"J Occup Health"},{"issue":"3","key":"465_CR7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3109\/15563651003627777","volume":"48","author":"CC Lin","year":"2010","unstructured":"Lin CC, Yang CC, Ger J, Deng JF, Hung DZ. Tetramethylammonium hydroxide poisoning. Clin Toxicol. 2010;48(3):213\u20137.","journal-title":"Clin Toxicol"},{"issue":"6","key":"465_CR8","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1177\/0748233710391990","volume":"27","author":"CH Lee","year":"2011","unstructured":"Lee CH, Wang CL, Lin HF, Chai CY, Hong MY, Ho CK. Toxicity of tetramethylammonium hydroxide: review of two fatal cases of dermal exposure and development of an animal model. Toxicol Ind Health. 2011;27(6):497\u2013503.","journal-title":"Toxicol Ind Health"},{"issue":"2","key":"465_CR9","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1539\/joh.12-0143-CS","volume":"55","author":"SH Park","year":"2013","unstructured":"Park SH, Park J, You KH, Shin HC, Kim HO. Tetramethylammonium hydroxide poisoning during a pallet cleaning demonstration. J Occup Health. 2013;55(2):120\u20134.","journal-title":"J Occup Health"},{"issue":"12","key":"465_CR10","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1080\/15563650.2018.1533727","volume":"56","author":"DD Gummin","year":"2018","unstructured":"Gummin DD, Mowry JB, Spyker DA, Brooks DE, Osterthaler KM, Banner W. 2017 annual report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 35th annual report. Clin Toxicol. 2018;56(12):1213\u2013415.","journal-title":"Clin Toxicol"},{"issue":"7","key":"465_CR11","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1080\/10408444.2018.1493085","volume":"48","author":"AH Hall","year":"2018","unstructured":"Hall AH, Mathieu L, Maibach HI. Acute chemical skin injuries in the United States: a review. Crit Rev Toxicol. 2018;48(7):540\u201354.","journal-title":"Crit Rev Toxicol"},{"issue":"2","key":"465_CR12","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.burnso.2018.03.001","volume":"2","author":"P Kulkarni","year":"2018","unstructured":"Kulkarni P, Jeffery S. The effects of the use of Diphoterine\u00ae solution on chemical burns in the Tarapur industrial complex, India. Burns Open. 2018;2(2):104\u20137.","journal-title":"Burns Open"},{"issue":"1","key":"465_CR13","first-page":"9","volume":"28","author":"SD Zack-Williams","year":"2015","unstructured":"Zack-Williams SD, Ahmad Z, Moiemen NS. The clinical efficacy of Diphoterine(R) in the management of cutaneous chemical burns: a 2-year evaluation study. Ann Burns Fire Disasters. 2015;28(1):9\u201312.","journal-title":"Ann Burns Fire Disasters"},{"key":"465_CR14","doi-asserted-by":"publisher","unstructured":"Fortin JL, Fontaine M, Bodson L, Depil-Duvala A, Bitar MP, et al. Use of an Amphoteric Solution in Eye, Skin and Oral Chemical Exposures: Retrospective Multicenter Clinical Case Series. J Clin Toxicol. 2017;7:343. https:\/\/doi.org\/10.4172\/2161-0495.1000343.","DOI":"10.4172\/2161-0495.1000343"},{"issue":"5","key":"465_CR15","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1006\/phrs.1999.0620","volume":"41","author":"SM Jankovic","year":"2000","unstructured":"Jankovic SM, Beleslin DB. Effects of nicotine, dimethylphenylpiperazinium and tetramethylammonium on smooth muscles from feline and human gastric corpus. Pharmacol Res. 2000;41(5):577\u201383.","journal-title":"Pharmacol Res"},{"issue":"21","key":"465_CR16","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1016\/0006-2952(72)90217-1","volume":"21","author":"S Adamic","year":"1972","unstructured":"Adamic S. Effects of quaternary ammonium compounds on choline entry into the rat diaphragm muscle fibre. Biochem Pharmacol. 1972;21(21):2925\u20139.","journal-title":"Biochem Pharmacol"},{"issue":"6 Pt 1","key":"465_CR17","doi-asserted-by":"publisher","first-page":"C1414","DOI":"10.1152\/ajpcell.1995.268.6.C1414","volume":"268","author":"RH Kennedy","year":"1995","unstructured":"Kennedy RH, Wyeth RP, Gerner P, Liu S, Fontenot HJ, Seifen E. Tetramethylammonium is a muscarinic agonist in rat heart. Am J Physiol. 1995;268(6 Pt 1):C1414\u20137.","journal-title":"Am J Physiol"},{"issue":"1","key":"465_CR18","first-page":"18","volume":"152","author":"GL Gebber","year":"1966","unstructured":"Gebber GL, Volle RL. Mechanisms involved in ganglionic blockade induced by tetramethylammonium. J Pharmacol Exp Ther. 1966;152(1):18\u201328.","journal-title":"J Pharmacol Exp Ther"},{"issue":"9612","key":"465_CR19","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0140-6736(07)61202-1","volume":"371","author":"M Eddleston","year":"2008","unstructured":"Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597\u2013607.","journal-title":"Lancet."},{"issue":"7","key":"465_CR20","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/0041-0101(89)90037-8","volume":"27","author":"U Anthoni","year":"1989","unstructured":"Anthoni U, Bohlin L, Larsen C, Nielsen P, Nielsen NH, Christophersen C. Tetramine: occurrence in marine organisms and pharmacology. Toxicon. 1989;27(7):707\u201316.","journal-title":"Toxicon"},{"issue":"7","key":"465_CR21","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.burns.2012.02.027","volume":"38","author":"CL Wu","year":"2012","unstructured":"Wu CL, Su SB, Lien HY, Guo HR. The role of the chemical burns caused by hydroxide ion in the toxicity of dermal exposure to tetramethylammonium ion in a rat model. Burns. 2012;38(7):1051\u20137.","journal-title":"Burns"},{"key":"465_CR22","unstructured":"Private communication: Dermal exposure of TMAH resulted in out of hospital cardiac arrest. 2017."},{"issue":"4","key":"465_CR23","first-page":"228","volume":"44","author":"AH Hall","year":"2002","unstructured":"Hall AH, Blomet J, Mathieu L. Diphoterine for emergent eye\/skin chemical splash decontamination: a review. Vet Hum Toxicol. 2002;44(4):228\u201331.","journal-title":"Vet Hum Toxicol"},{"issue":"2","key":"465_CR24","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3109\/15569521003661288","volume":"29","author":"C Fosse","year":"2010","unstructured":"Fosse C, Mathieu L, Hall AH, Bocchietto E, Burgher F, Fischbach M, et al. Decontamination of tetramethylammonium hydroxide (TMAH) splashes: promising results with Diphoterine in vitro. Cutan Ocul Toxicol. 2010;29(2):110\u20135.","journal-title":"Cutan Ocul Toxicol"},{"issue":"2","key":"465_CR25","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.burns.2004.09.001","volume":"31","author":"H Merle","year":"2005","unstructured":"Merle H, Donnio A, Ayeboua L, Michel F, Thomas F, Ketterle J, et al. Alkali ocular burns in Martinique (French West Indies) evaluation of the use of an amphoteric solution as the rinsing product. Burns. 2005;31(2):205\u201311.","journal-title":"Burns"},{"issue":"2","key":"465_CR26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.burnso.2018.03.001","volume":"2","author":"PJS Kulkarni","year":"2018","unstructured":"Kulkarni PJS. The effects of the use of Diphoterine\u00ae solution on chemical burns in the Tarapur industrial complex, India. Burns Open. 2018;2(2):104\u20137.","journal-title":"Burns Open"},{"issue":"8","key":"465_CR27","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1007\/s00417-019-04350-x","volume":"257","author":"N Wiesner","year":"2019","unstructured":"Wiesner N, Dutescu RM, Uthoff D, Kottek A, Reim M, Schrage N. First aid therapy for corrosive chemical eye burns: results of a 30-year longitudinal study with two different decontamination concepts. Graefes Arch Clin Exp Ophthalmol. 2019;257(8):1795\u2013803.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"2","key":"465_CR28","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/BF00512059","volume":"328","author":"C Neef","year":"1984","unstructured":"Neef C, Meijer DK. Structure-pharmacokinetics relationship of quaternary ammonium compounds. Correlation of physicochemical and pharmacokinetic parameters. Naunyn Schmiedebergs Arch Pharmacol. 1984;328(2):111\u20138.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00465-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40360-020-00465-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00465-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T17:41:13Z","timestamp":1606758073000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-020-00465-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["465"],"URL":"https:\/\/doi.org\/10.1186\/s40360-020-00465-8","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]},"assertion":[{"value":"10 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable. A retrospective observational chart review study of this type requires no approval from the IRB of the authors\u2019 institutions, in accordance with Taiwanese national regulations. All data is in a closed databank maintained by the PCC-Taiwan. No administrative approvals are required for the staff of PCC-Taiwan to access this closed databank.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AHH is a paid consultant for Laboratoire Prevor, Valmondois, France, manufacturer of Diphoterine\u00ae solution. JFD is a part time consultant for Prevor. No potential conflict of interest was reported by any of the other coauthors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"83"}}