Annals of Occupational and Environmental Medicine

A Case of Acute Toxic Hepatitis induced by brief exposure to Dimethylformamide: Jong Rae Roh, Jin Gun Sohn, Jin Ha Kim, Sun Ja Park; Korean Journal of Occupational and Environmental Medicine 2005;17(2):144-148. Published online June 30, 2005; DOI: https://doi.org/10.35371/kjoem.2005.17.2.144

Dimethylformamide (DMF), a widely used industrial solvent, has been reported to induce subtle to clinically overt hepatotoxicity. Liver injury due to occupational exposure through inhalation and skin contact has been sporadically reported. We report a 23-year-old male who developed intermittent abdominal pain, anorexia, nausea, vomiting, chest discomfort, and general weakness for 4 days after working in a plastic-coated-glove factory. An acute hepatitis episode occurred after working in an enclosed workplace for 3 days. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis, could be excluded or were considered to be unlikely. Based on occupational history, serological examination and serial liver function examinations, the case was compatible with DMF-induced acute toxic hepatitis. Hepatotoxicity due to occupational exposure to solvents (e.g., DMF) should be considered in any patient with unexplained hepatitis. The fast improvement of the clinical symptoms and the progressive normalization of the liver function tests once the DMF exposure has been stopped, supports the diagnosis.

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The potential health risks of N,N‐dimethylformamide: An updated review
Shu‐Jun Hong, Xiu‐Ning Zhang, Zhan Sun, Tao Zeng
Journal of Applied Toxicology.2024;[Epub] CrossRef
A case report of toxic hepatitis caused by chloroform in automotive parts manufacturer coating process
Jong Hyun Hwang, Jung Il Kim
Annals of Occupational and Environmental Medicine.2022;[Epub] CrossRef
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Archives of Environmental & Occupational Health.2020; 75(3): 127. CrossRef
Compensation for Occupational Diseases by Chemical Agents in Korea
Soon-Chan Kwon, Soo-Yong Roh, Ji-Hoon Lee, Eun-A Kim
Journal of Korean Medical Science.2014; 29(Suppl): S78. CrossRef
Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology
Tae Hyun Kim, Sang Geon Kim
Safety and Health at Work.2011; 2(2): 97. CrossRef

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Seasonal Variations of the Urinary N-Methylformamide Concentration among Workers at a Synthetic Leather Factory: Kwang Young Lee, Joo Hyun Byeon, Hae Rhan Song, Jin Ha Kim, Kwang Wook Ko, Yong Hwan Lee; Korean Journal of Occupational and Environmental Medicine 2003;15(2):162-172. Published online June 30, 2003; DOI: https://doi.org/10.35371/kjoem.2003.15.2.162

Abstract PDF

OBJECTIVES
This study was carried out to identify seasonal variations of urinary concentrations of N-methylformamide (NMF) among workers employed at a synthetic leather factory.
METHODS
Study subjects consisted of 16 male and 6 female workers who were involved in the direct treatment of dimethylformamide (DMF) in a synthetic leather factory. By using health examination data and the results of air measurements and biologic monitoring conducted in February and July, 2001, we identified seasonal variations of the DMF concentrations in the air and NMF concentrations in urine.
RESULTS
1) In winter and summer, average temperatures at the working sites were 3.2 degrees C and 26.5 degrees C, respectively and average humidities were 35.4 % and 84.5 %, respectively. 2) Airborne DMF concentrations were not significantly different between summer (13.78 ppm) and winter (11.55 ppm). 3) NMF concentrations in urine were found to be significantly higher in summer (96.09 mg/g creatinine) than in winter (31.23 mg/g creatinine) (p<0.001).
CONCLUSIONS
The seasonal difference in the urinary excretion values of NMF may be due to increased dermal absorption of DMF with the higher ambient temperature and humidity in summer and the increased area of exposed skin.

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Risk assessment of N,N-dimethylformamide on residents living near synthetic leather factories
Qingyu Zhang, Chanke Huang, Yumei Wei, Qi Zhu, Weili Tian, Cui Wang
Environmental Science and Pollution Research.2014; 21(5): 3534. CrossRef
Assessment of correlation between markers of ambient monitoring and biological monitoring of dimethylformamide for workers in synthetic leather manufacturing factories in Korea
Yang In Hwang, Mi-Young Lee, Yun Kyung Chung, Eun A Kim
Analytical Science and Technology.2013; 26(5): 315. CrossRef
Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology
Tae Hyun Kim, Sang Geon Kim
Safety and Health at Work.2011; 2(2): 97. CrossRef

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The Metabolism and Liver Toxicity of N, N-dimethylformamide in the Isolated Perfused Liver: Sang Baek Koh, Bong Suk Cha, Myung Guen Kang, Sang Yeol Koh, Jung Woo Lee, Sang Ok Kwon; Korean Journal of Occupational and Environmental Medicine 1997;9(2):217-229. Published online June 30, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.2.217

Abstract PDF

N, N-dimethylformamide (DMF) is a solvent which is widely used in the industrial workplace. It causes the liver damages to the chronically exposed workers and is also well known as the harzadous material to generate occupational malignancies. DMF is mainly metabolized into N-hydroxymethyl-N-methylformamide (HMMF) by the microsomal cytochrome p-450. HMMF breaks down to NMF. However, the detailed mechanism of its toxicity are unknown. In this experiment, the metabolism and the toxicity of DMF was investigated using an isolated perfumed liver model. DMF (0, 10, 25mM) were added into recirculating perfusate of the isolated perfused rat liver. Samples were collected at 0, 30, 45, 60, 75, 90 minutes from inferior vena cava. The gas-chromatography was used to analyze the metabolite of DMF, The changes in the oxygen consumption rate by DMF were monitored during perfusion. The enzyme activity (AST, ALT, LDH) in the perfusate were treasured to find out whether DMF causers hepatotoxicity. As perfusion continued, DMF concentration in the perfusate decreased, and NMF 1.16mM was detected. The oxygen consumption rate increased both at 10mM and 25mM DMF concentration. However, when SKF 525A, a known inhibitor of cytochrome p-450, had been pretreated (300uM before DMF addition, the oxygen consumption rate was significantly inhibited, indicating that cytochrome p-450 system is responsible for the conversion to NMF. With DMF addition, the activity of AST, ALT, and LDH significantly increased time dependently and dose dependently. However, the pretreatment of perfused liver with SKF 525A shoved that the release of AST, ALT and LDH was inhibited. In summary, it is found that DMF is metabolized to NMF in liver, and that cytochrome p-450 mono-oxygenase is suggested to play a role in the biotransformation of NMF. The time course of BMF toxicity in relation to NMF formation is compatible with hypothesis that the hepatotoxicity of DMF is mediated via NMF. Further study combined with in vivo experiment through the toxicological approaches is expected.

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Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology
Tae Hyun Kim, Sang Geon Kim
Safety and Health at Work.2011; 2(2): 97. CrossRef

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A Suspicious Case of Dimethylformamide Induced Fulminant Hepatitis in Synthetic Leather Workers: Soo Keun Kim, Soo Jin Lee, Kyou Chull Chung; Korean Journal of Occupational and Environmental Medicine 1995;7(1):186-190. Published online February 28, 1995; DOI: https://doi.org/10.35371/kjoem.1995.7.1.186

Abstract PDF

A man who worked in the synthetic leather manufacturing plant for 3 months died at November 3. Author review the medical record, the death certificate, and interviewed his wife and the doctor who treated him. His major job was DMF handling. At the working place, he felt severe health problem, and admitted to the hospital via emergency clinic. He complained severe abdominal pain and showed jaundice and ascites, He suffered hepatic coma and respiratory insufficiency from fulminant hepatitis from 19th days after admission. Drug abuse, hepatitis (A, B, C), and alcoholic hepatitis were rule out with his history and serological study data, As a result, author couldn't find any cause of death, but fuIminant hepatitis from DMF toxicity.

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Changes of 30 years in the recognized occupational diseases of Korea: Lessons from the system change perspective
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International Journal of Environmental Research and Public Health.2018; 15(3): 503. CrossRef
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Journal of Korean Medical Science.2014; 29(Suppl): S66. CrossRef
Assessment of correlation between markers of ambient monitoring and biological monitoring of dimethylformamide for workers in synthetic leather manufacturing factories in Korea
Yang In Hwang, Mi-Young Lee, Yun Kyung Chung, Eun A Kim
Analytical Science and Technology.2013; 26(5): 315. CrossRef
Clinical Outcomes of Occupational Exposure to N,N-Dimethylformamide: Perspectives from Experimental Toxicology
Tae Hyun Kim, Sang Geon Kim
Safety and Health at Work.2011; 2(2): 97. CrossRef
Occupational Diseases in Korea
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Journal of Korean Medical Science.2010; 25(Suppl): S4. CrossRef
Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers
Hae-Kwan Cheong, Eun A Kim, Jung-Keun Choi, Sung-Bong Choi, Jeong-Ill Suh, Dae Seob Choi, Jung Ran Kim
Environmental Health Perspectives.2007; 115(1): 107. CrossRef

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