Toxicity evaluation of transdermal absorption of tetramethylammonium hydroxide (TMAH) in the rat model

• Main Authors: Chunh-Hsun Lee, 李忠勳
• Other Authors: Chi-Kung Ho
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/55557839727529908688

碩士 === 高雄醫學大學 === 職業安全衛生研究所 === 97 === Background : TMAH (tetramethylammonium hydroxide) is a kind of corrosive alkaline solution. It was widely used in manufacturing process in semiconductor industry, photoelectronic industry and MRI contrast agent. However, two operators died after exposed to TMAH without proper personal protection within 2 days in Kaohsiung on February 16, 2007. The main structure of TMAH is TMA (tetramethylammonium ion) which is a weak inhibitor of acetylcholinesterase. In these two mortality cases after exposed to TMAH, no obvious decreasing concentration of acetylcholinesterase were found in their blood samples. TMA can affect these small, rapidly moving muscles such as those of the fingers and eyes first, and those of the limbs, neck and trunk are involved later. The intercostal muscles and the diaphragm are the last to be paralyzed. Respiratory depression seems the most possible reason to cause death, but the real mechanism of toxicity is still unclear. Material & Methods : We established the animal mode for the skin exposure of 2.38 % and 25% TMAH and the physiologic parameters were recorded. Skin irritation test, lethal dose, and possible antidotes were also performed. The Sprague-Dawley male rats’ (weight 300-350 g) dorsal hairs were shaved, and the lethal dosage of THAH was measured by subcutaneous injection and daubing TMAH on the skin. The physiological parameters were recorded at different time points by the blood pressure and breath monitors. The measurement of TMA concentration in the plasma was analyzed by the LC/MS/MS. The concentration of blood acetylcholinesterase was measured by immunoturbidimetric method. According to the criteria of Draize (1959) for classification of skin reaction, the change of skin color after the exposure of TMAH for 4 hours was used as an index of the skin irritation test. Atropine was tested as an antidote. Results: The LD50 of TMAH after skin exposure to 2.38% and 25%, is 89.75 mg/kg、34.17 mg/kg respectively. The 95% confidence intervals of LD50 is 53.20-111.43 mg/kg and 20.73-54.05 mg/kg respectively. The LD50 of TMAH after intra-peritoneal injection is 14.26 mg/kg and the 95% confidence intervals of LD50 is 9.16 - 20.51 mg/kg. After skin exposure to TMAH for 60 minutes, the blood concentration of TMA reached the peak level. The blood concentration of cholinesterase of each group decreased with time, but there was no obviously different within each group. TMAH could exist in the plasma in a prototype through skin absorption. Microscopically, it showed the skin damage progressed with time and concentration of TMAH. Progressing dyspnea following with respiratory failure and convulsion-like movement were observed after skin exposure to TMAH. Conclusions: Respiratory depression is the main cause of death after exposure to TMAH. TMAH could exist in the plasma in a prototype through skin absorption. However, the inhibition of respiratory function is not totally connected to the concentration of TMA and cholinesterase. Other possible neurologic toxicity may be considered. Further study is necessary.