From: Eugene Ngai <eugene_ngai**At_Symbol_Here**COMCAST.NET>
Subject: Re: [DCHAS-L] TMAH Incident
Date: Sun, 17 Jan 2021 02:22:50 -0500
Reply-To: ACS Division of Chemical Health and Safety <DCHAS-L**At_Symbol_Here**Princeton.EDU>
Message-ID: 003e01d6eca1$90a65d00$b1f31700$**At_Symbol_Here**

Dr. Hall


This was a very interesting article. Please send me an e-mail at eugene_ngai**At_Symbol_Here**



From: ACS Division of Chemical Health and Safety <DCHAS-L**At_Symbol_Here**Princeton.EDU> On Behalf Of Alan Hall
Sent: Saturday, January 16, 2021 7:38 PM
To: DCHAS-L**At_Symbol_Here**Princeton.EDU
Subject: Re: [DCHAS-L] TMAH Incident


Et al,


You might consider our recent article regarding TMAH exposures in a retrospective observational study (data also from Taiwan):


Huang C-K, Hall AH, Wu M-L et al.  Presentation of tyetramethylammonium hydroxide dermal exposure and the valuable potential of diphoterine solution in decontamination:  a retrospective observational study.  BMC Pharmacol Toxicol 2020; 21:83; doi:  101186/s40360-020-00465-8.


It appears that the TMAH causes both base corrosive skin/eye injuries and that the compound readily dissociates into the TMA+ cation and the OH- anion.  The anion causes skin injury which allows the TMA+ ion to more easily penetrate the skin, be absorbed, and cause systemic cholinergic agonist toxicity, sometimes fatal.  It seems that this is analogous to the effects of HF, where the H- anion causes dermal injury and allows deeper penetration and absorption of the F+ ion which causes severe and often fatal systemic toxicity.


In both cases, early skin decontamination must be done, (potable water does not seem to be efficacious) and as the TMAH cholinergic toxicity mainly manifests as respiratory and cardiac failure, supplemental oxygen (by endotracheal tube if needed) and mechanical ventilation are required in severe cases.  Atropine does not seem to be efficacious.  So far to my knowledge, no one has tried acetylcholinesterase reactivators such as 2-PAM chloride, Toxigonin, or HI-6.  Tetramethylammonium chloride has little systemic toxicity in experimental animals, unless the skin first been injured by exposure to a significant skin corrosive substance, which strongly suggests that TMA+ is not well absorbed through uninjured skin.


Our group has recently performed 2 studies of the skin penetration of TMAH in a human skin explants model, one of which I am currently writing up for publication.  We will later submit the second study for publication.


I would be happy to discuss this issue with anyone interested off-line.


Disclaimer:  I am a paid consultant to Laboratoire Prevor, Vallmondois, France, manufacturer of Diphoterine(R) solution.



Alan H. Hall, M.D.

email:  OldEDDoc**At_Symbol_Here**

Phone:  (817) 818-3298


On Sat, Jan 16, 2021 at 3:29 PM NEAL LANGERMAN <neal**At_Symbol_Here**> wrote:


Thank you for this update on TMAH. Has a metabolic mechanism for this very high toxicity been proposed? A related compound, tetramethyl ammonium chloride, has a surprisingly low aquatic toxicity.





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From: ACS Division of Chemical Health and Safety <DCHAS-L**At_Symbol_Here**Princeton.EDU> On Behalf Of Eugene Ngai
Sent: Saturday, January 16, 2021 10:59 AM
To: DCHAS-L**At_Symbol_Here**Princeton.EDU
Subject: [DCHAS-L] TMAH Incident


Last week there was a serious incident involving Tetramethylammonium Hydroxide (TMAH), a chemical that is widely used in the Semiconductor Fab. It is not known what the final outcome is of the 6 individuals that were exposed, 2 were serious. In many large Fabs TMAH is pipe through the facility at various concentrations.

Of all the reactive/pyrophoric or toxic chemicals used in the Fab, TMAH is one of the top 5 that I have a concern with as there appears to be no effective medical treatment protocol. I spoke to Dr. Wu at my 2008 training class on Trichlorosilane Safety and ER in Taiwan.  As a consultant to the Taiwan Poison Control Center he has been involved in TMAH incidents, 3 of which were fatal. He spoke of one in which a worker was alone and was splashed with a 25% solution. He immediately went to the safety shower. He was found 15 minutes later barely conscious. Prior to arrival at the hospital he went into cardiac arrest. He was resuscitated but he slipped into a coma and died 8 days later.


High concentration (25%) exposure of 7% of the body is fatal! Even lower concentration can also be


Park et al., J Occup Health, 2013


  • 39 yr old male splashed 8.75% TMAH on his hands, arms and legs
  • 12% body surface area affected
  • Continued working and went to the shower room 25 mins after the spill
  • He was found dead outside the shower ~60 mins later
  • Second degree burns on skin


IBM Medical and Safety professionals conducted a detailed review of incidents as well a sponsored extensive animal dermal exposure testing. They presented their findings at the 2011 Semiconductor Environmental Safety and Health Association (SESHA) Conference with an update in 2018. I have summarized the LG Display incident as well as the 2011 IBM presentation to educate those that have limited knowledge of TMAH.  The presentation was updated in 2018. It can be downloaded for free to SESHA members. Membership is free.


My summary can be found on my website


Eugene Ngai

Chemically Speaking LLC


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