디메틸포름아미드(dimethylformamide)에 의한 독성 간염 1례

정인성,이충원 啓明大學校 醫科大學 2001 계명의대학술지 Vol.20 No.2

Dimethylformamide is a solvent used extensively in the chemical industry. The effect of it's exposure in human are not well documented. However, liver is the main organ afflicted after acute or chronic exposure. We report a patient with toxic hepatitis induced by dimethylformamide. His job was textile coating. He complained fatigue, alcohol intolerance, facial flushing and nausea. He had abnormally high serum aminotransferase level. The amount of urinary excretion of N-methylformamide was 300 ㎍/㎖. Possibilities of viral hepatitis, autoimmune hepatitis and alcoholic hepatitis were ruled out by his personal history and serological study. Liver function became normal after management for a month.

Dimethylformamide가 사람 혈청의 과산화지질 농도와 Superoxide dismutase 활성도 변화에 미치는 영향

김기웅,최정근,김태균,송문기,고경선,손남석,조영숙,김소연,김희곤 한국독성학회 1996 Toxicological Research Vol.12 No.1

The variation in the enzyme activities of human liver usually represents the particular physiological conditions of each individuals. Thus, we investigated the variation in the activities of SOD, HR and LPO of (1) non-exposed workers (56 subjects), and (2) exposed workers to DMF (43 subjects) in synthetic leather process. Serum levels of enzyme activities of exposed workers (AST:$30.26{\pm}20.041$U/L, ALT:$32.72{\pm}23.393$U/L, GGT:$28.47{\pm}18.635$ U/L, ALP:$81.77{\pm}34.879$ U/L)were slightly higher than those in nonexposed workers (AST:$24.00{\pm}9.441$ U/L, ALT:$23.89{\pm}18.305$U/L, GGT:$21.95{\pm}17.970$U/L, ALP:$70.84{\pm}24.678$U/L), but only the level of ALT was statistically significant (p< 0.05). Serum levels of LDH, TRF and CHOL in non-exposed workers were slightly higher than those of exposed workers. However, they were not statistically significant (p > 0.05). Serum levels of HR and LPO of the exposed workers appeared to be reduced, but not those of the non-exposed workers. The SOD activities of exposed workers were also slightly higher than those of non-exposed workers, but the results were not statistically significant (p > 0.05). The level of HR was increased with age, but the SOD level was not. These results suggest that the intermittent exposure to DMF at time-weighted average (TWA) level (10 ppm/$m^3$) has affected on the activities of enzymes such as AST, ALT, TRF, but not on the generation of HR, activity of SOD. However, if high dose of DMF was used, there would be severe effects for the generation of HR and LPO.

합성피혁제조업에서 취급하는 DMF, MEK, Toluene의 단일과 혼합물질 상태에 따른 물리, 화학적 특성 변화

김기웅 ( Ki Woong Kim ),원용림 ( Yong Lim Won ),박동진 ( Dong Jin Park ),이정석 ( Jung Suk Lee ),한인수 ( In Soo Han ),이수희 ( Su Hee Lee ) 한국산업보건학회 2014 한국산업보건학회지 Vol.24 No.2

Objectives: It was known that workers in synthetic leather company are mainly co-exposed to dimethylformamide(DMF) with methyl ethyl ketone(MEK) or toluene(TOL) instead of a single dimethylformamide. This study was examined to the physico-chemical properties in single DMF and binary mixture DMF with MEK or TOL. Materials: Physico-chemical properties were measured by Korean and American Standard Test Methods. Results: Boiling point, specific gravity and flash point in single DMF were significantly higher than binary mixture DMF with MEK or TOL and such difference was dependent on the mixing ratio of MEK and TOL, and low explosion limit in binary mixture DMF with TOL was only significantly lower than single DMF. However, Reid vapor pressure had significantly higher in binary mixture DMF with MEK or TOL compared with single DMF. Conclusions: Our results demonstrate that the binary mixture DMF with MEK or TOL synergistically increases volatilization of DMF. It was concluded that the interaction between DMF and MEK and/or TOL might play a key role in the volatilization process of DMF under environmental conditions of workplace.

Preparation of heteroatom isomorphously substituted MEL zeolite membranes for pervaporation separation of dimethylformamide/water mixtures

Qigang Wu,Rong Xu,Hui Shao,Jing Zhong,Xiuxiu Ren,Zhengzhong Zhou 한국화학공학회 2021 Korean Journal of Chemical Engineering Vol.38 No.10

The recovery of dimethylformamide (DMF) by pervaporation is less energy intensive and more economical than the traditional distillation method. High/pure silica zeolite is a typical organics perm-selective material for pervaporation membrane due to its hydrophobic nature, demonstrating great potential for recovering organic components from aqueous solutions. In this study, as an attempt to further enhance the membrane hydrophobicity, titanium and zirconium- substituted MEL type zeolite membranes (Ti-silicalite-2 and Zr-silicalite-2) were synthesized on the -Al2O3 discs by a secondary growth method. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) results confirmed the isomorphous substitution of the MEL framework by Ti and Zr atoms. The effects of isomorphous substitution, feed temperature and concentration on the DMF recovery performance were investigated via systematically designed pervaporation experiments. The fluxes and separation factors both increased with the isomorphous substitution of heteroatom, as well as increasing feed temperature and decreasing feed concentration. The Ti-silicalite-2 membrane exhibited a high separation factor of 6.4 with a total flux of 0.98 kg·m2·h1 for a 5wt% DMF/water feed at 343K.

Effect of Dimethylformamide on Post-Thaw Motility, Acrosome Integrity, and DNA Structure of Frozen Boar Sperm

황유진,양재훈,김상옥,김보경,최선규,박춘근,김대영 사단법인 한국동물생명공학회 2009 한국동물생명공학회지 Vol.24 No.4

The beneficial effect of glycerol as a cryoprotectant, especially for sperm cryopreservation, has been shown in many studies. However, glycerol is toxic to living cells, and boar sperm in particular show greater sensitivity to glycerol than sperm from other domestic animals. Amides have been studied as alternative cryoprotectants for freezing stallion sperm. Sperm frozen in methylformamide or dimethylformamide as cryoprotectants show similar motility when thawed compared with sperm frozen in glycerol. We evaluated the cryoprotective effects of dimethylformamide on boar sperm freezing. To test the effect of amides, the concentration of boar semen was adjusted to 109sperm/mL, and seminal plasma was removed using Hulsen solution. After centrifugation, the pellet was diluted in modified-Modena B extender. Lactose-egg yolk (LEY) extender was used as the cooling extender. The freezing extender was madeed aaddition of the optimal amount of glycerol and amides to LEY-Glycerol-Orvus ES Paste extender, and this extender was used for the second dilution. Diluted sperm were frozen in liquid nitrogen using the 0.5 mL straw method. Sperm frozen in extender with glycerol as a cder ol were compared with those frozen in extender including the different amides. Sperm were tested for motility, viability, the sperm chromatin structure assay, and normal apical ridge after thawing. The percent of motile sperm diluted in glycerol was as high as that in the stallion study (61%). Dimethylformamide showed positive effects on sperm quality and was better than glycerol. Methylformamide provided similar sperm quality as glycerol. Therefore, dimethylformamide is useful for reducing cryoinjury in boar sperm and is expected to be useful as an alternative cryoprotectant.

여과분리형 생물반응조를 이용한 디메틸포름아미드 제거 특성

정용준 ( Yong Jun Jung ),이태관 ( Tae Kwan Lee ) 한국수처리학회 2010 한국수처리학회지 Vol.18 No.6

The removal properties of dimethylformamide were examined with filtration bio-reactor equipped with filter media. The formation of sludge cake layers to get enough good quality of the effluent by filtration was obtained within 2 minutes after aeration cleaning, where the filtrate showed over 80 NTU at the initial period and below 10 NTU at the stable filtration period. The filtration time over 2,500 ㎎/L of DMF concentration was shown more than 80 minutes, but it showed less than 60 minutes below 1,000 ㎎/L of DMF concentration. The removal efficiency of TOC was over 90% when the concentration of the influent was increased. SS and Colority of the filtrate were shown the similar removal pattern with the filtration time. Therefore, this system may be expected to the treatment of dimethylformamide wastewater.

Dimethylformamide 취급 근로자에서의 CYP2E1, GSTM1, GSTT1 유전자 다형성과 N-methylformamide 배설량간의 관련성

김재일,이충한,이용환 KOSIN UNIVERSITY COLLEGE OF MEDICINE 2006 高神大學校 醫學部 論文集 Vol.21 No.1

Background: N,N-dimethylformamide (DMF) has excellent solvent properties and is used intensively in the production of synthetic leather and resins. It has known to induce hepatotoxicity in human and animal by absorbing it through the lungs and skin. The metabolic transformation of DMF takes place mainly in the liver, with the aid of microsomal enzyme systems including cytochrome P450 (CYP), and glutathione S-transferase (GST). In metabolic studies and biological monitoring, urinary concentrations of metabolites are measured and expressed as N-methylformamide (NMF). This study examined the associations of the genetic polmorphism of CYP2E1. GSTM1 and GSTT1 with DMF metabolism. Methods: The subjects were 30 workers who exposed to DMF in a synthetic leather factory. Their urinary samples were collected and NMF concentrations were measured. Also, DMF concentrations in air were measured by personal air sampler during thier work. Genotypes of CYP2E1, GSTM1 and GSTT1 were investigated using PCR-RFLP or multiolex PCR methods with DNA extracted from venous blood. Effects of the polymorphisms of CYP2E1, GSTM1 and GSTT1 on DMF metabolism were analyzed. Results: The frequency of c1/c1 and c1/c2 genotypes for CYP2E1 were 76.6% and 23.3%, respectively. GSTM1 was deleted in 53.3% and GSTT1 deletion rate was 40.0%. In the group of GSTM1 deletion, mean urinary NMF concentrations (95.2 mg/g creatinine) were significantly higher than the undeleted group (45.3 mg/g creatinine, p=0.042). There were no significant differences of mean urinary NMF concentrations in the groups with the defferent genotypes of CYP2E1 and GSTT1. The distribution of CYP2E1, GSTM1 and GSTT1 genotypes by urinary NMF concentrations had not statistical significance. Conclusions: In GSTM1 deleted workers who exposed to DMF, mean urinary NMF concentration was higher than undeleted cases. GSTM1 deleted workers are seemed to be more susceptible to DMF toxicity. It is necessary to screen whether the workers have GSTM1 deleted genotype or not when they are arranged to their work place.

디메칠포름아미드에 의한 간기능 장해에 관한 연구

강성규,장재연,이경용,정호근 大韓産業醫學會 1991 대한직업환경의학회지 Vol.3 No.1

To investigate the liver dysfunction among workers exposed to dimethylformamide, 24 workers were examined on the liver transaminases and the urine metabolite. The results were as follows: 1. Nine of 24 workers examined had abnormal values in serum aspartate aminotransferase(AST), 5 in serum alanine aminotransferase (ALT), 1 in Υ-glutamyl transferase(Υ-GT). The possibilties of hepatitis due to other causes were excluded by the viral serologic tests and other results. 2. The urinary excretion values of N-methylformamide(NMF), metabolite of dimethylformamide(DMF) were over biological exposure index(BEI) in 4 of 24 workers. 3. The air concentration of dimethylformamide was over threshold limit values(TLV-TWA) in 1 of 5 workers sampled by personal air sampler. 4. The correlation coefficients between age, working part and the values of liver transaminases were not statistically significant.

적출간 관류법에 의한 N,N-dimethylformamide의 대사 및 간독성

고상열,이중우,고상백,권상옥,강명근,차봉석 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.2

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 perfused liver model. DEF(0, 10, 25mM) were added into recirculation 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 monitered during perfusion. The enzyme activity(AST, ALT, LDH) in the perfusate were measured to find out whether DMF causes 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, indication 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 showed 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 p0450 mono-oxygenase is suggested to play a role in the biotransformation of NMF. The time course of DMF toxicity in relation to NMF formation is compatible with hypothesis that the hepatotoxicity 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.

N, N-dimethylformamide 취급근로자의 유해위험 정보 인식도 조사

양정선 ( Jeong Sun Yang ),임철홍 ( Cheol Hong Lim ),이혜진 ( Hae Jin Lee ) 한국산업위생학회 2011 한국산업보건학회지 Vol.21 No.2

Object: we investigated some factors which can affect workers` comprehension of chemical hazard information and their actions to protect themselves from the hazard. Method: Comprehension score of chemical hazard information and the rate of wearing personal protective equipment (PPE) was surveyed for the 109 workers from 15 factories who were exposed to N, N-dimethylformamide. Difference of the worker`s comprehension score of hazard information was analyzed by education interval, work duration and the way of occupational safety and health management between self-managed or sub-contracted. Result: Mean comprehension score of N, N-dimethylformamide hazard, which was given as a short quiz composed of 10 "true" or "false" problems, was 65%. Mean percentage of wearing PPE was improved as the education program was done within a month but decreased after 6 months. Eighty seven % of workers got the chemical hazard information from the material safety data sheet placed at workplace. Conclusion: Education interval and comprehension score affected the rate of wearing PPE. The way of occupational safety and health management self-managed or sub-contracted did not affect the workers` comprehension score on hazard information nor the rate of wearing PPE.