title: Toxicity of tetramethylammonium hydroxide: review of two fatal cases of dermal exposure and development of an animal model.
abstract: To document two cases of patients who were fatally exposed to tetramethylammonium hydroxide (TMAH) on the skin and to establish a rat model to investigate the effects of dermal exposure to TMAH. The charts of two workers who died from occupational accidental exposure to TMAH were reviewed. The 4-hour lethal dose (LD₅₀) of TMAH was determined by applying solutions mimicking the two most common industrially used concentrations (2.38% and 25%) of TMAH to the skin of Sprague-Dawley rats. Exposure of the rat's skin to 2.38% or 25% TMAH generated LD₅₀ values of 85.9 mg/kg and 28.7 mg/kg, respectively. Application of either concentration of TMAH to the skin produced a rapid, significant increase in the rate of respiration. The serum concentrations of tetramethylammonium (TMA) also changed significantly with time of exposure to both concentrations of TMAH. The level of blood urea nitrogen decreased significantly in rats exposed to the 2.38% TMAH, and rats exposed to the 25% solution had a significant decrease in the serum concentration of sodium. Injection of atropine after 5 minutes of exposure did not significantly overcome any of the toxic effects observed with either solution of TMAH. The preliminary results in the rat model indicated that the lethality of TMAH cannot be fully explained by the severity of the patients' chemical burns, and the physiologic effects on respiratory and kidney functions were probably involved.
authors.affiliation: Department of Emergency Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan. chlee82er@yahoo.com.tw
authors.forename: Chung-Hsun
authors.initials: CH
authors.lastname: Lee
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Wang
authors.forename: Hsiu-Fen
authors.initials: HF
authors.lastname: Lin
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Hong
authors.forename: Chi-Kung
authors.initials: CK
authors.lastname: Ho
mesh_terms: D000062:Accidents, Occupational; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D005731:Ganglionic Stimulants / Q000506:poisoning*; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D000644:Quaternary Ammonium Compounds / Q000506:poisoning*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
chemical_list: D000931:Antidotes; D005731:Ganglionic Stimulants; D000644:Quaternary Ammonium Compounds; D001285:Atropine; C027917:tetramethylammonium