Liver disease associated with occupational exposure to the solvent dimethylformamide

Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Annals of internal medicine (Impact Factor: 17.81). 06/1988; 108(5):680-6. DOI: 10.7326/0003-4819-108-5-680
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to characterize an outbreak of liver disease among workers in a fabric coating factory; and to determine the outbreak's cause and natural history and strategies for clinical recognition, treatment, and prevention.
clinical-epidemiological investigation.
academic medical center, Occupational Medicine Clinic, and worksite.
fifty-eight of sixty-six workers participated in the study. All had standard liver function tests at least once. Forty-six workers completed a questionnaire; 27 had more extensive clinical evaluation for recognized liver abnormalities.
a plant-wide outbreak of liver disease was recognized after a new employee presented with signs and symptoms of hepatitis. Evaluation of the worksite showed that dimethylformamide, a widely used industrial solvent and known hepatotoxin, was being used to coat fabric in poorly ventilated areas without appropriate skin protection. No other major hepatotoxic exposure was identified. Overall, 36 of 58 (62%) workers tested had elevations of either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels. Enzyme abnormalities occurred almost exclusively in production workers (35 of 46 were abnormal), whereas only 1 of 12 nonproduction workers showed any elevations in enzyme levels (P less than 0.0001). Serologic tests excluded known infectious causes of hepatitis in all but 2 workers and changes characteristic of toxic liver injury were confirmed by histologic examinations of biopsy specimens from 4 workers. The ratio of AST to ALT levels was one or less in all but 1 worker. After modification of work practices and removal of workers most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms in most patients were seen, although some patients showed persistent elevations of enzyme levels.
an outbreak of toxic liver disease has been associated with exposure to dimethylformamide in the workplace. The diagnosis of toxic liver disease was established by the clinical histories, negative viral serologies, an enzyme pattern of ALT levels being greater than AST levels, epidemiologic data on coworkers, and liver biopsy specimens. The high prevalence of unsuspected liver enzyme abnormalities in these workers suggests that occupational liver disease may occur more frequently than is generally recognized.

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    • "DMF is an important solvent, it is privalry used as a solvent in the production of acrylic fibers and plastics. It is also used as a solvent in peptide coupling for pharmaceutics , in the development and production of pesticides and in the manufacture of adhesives, synthetic leathers, films and surface coatings [3]. Its separation from water is important and essential because of it is carcinogenic to human beings and other animals. "
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    ABSTRACT: In this study sodium alginate (NaAlg)/poly (vinyl pyrrolidone) (PVP) blend membranes were prepared and crosslinked with CaCl2 (0.1 Molarity (M)) for the separation of aqueous/dimethylformamide (DMF) mix- tures. Membranes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and their performance was examined by varying experimental parameters such as feed composition (0 - 100 wt%), operating temperature (30°C - 50°C) and membrane thickness (30 - 90 microme-ter (m)). Blending NaAlg with PVP, decreased separation factor whereas increased the permeation rate as the permeation temperature was increased in Vapor Permeation (VP) and Vapor Permeation with Tempera-ture Difference (TDVP) methods. In the TDVP method, the separation factors increased and the permeation rates decreased as the temperature of the membrane surrounding is decreased. The highest separation factor of 60 was obtained in TDVP method for 90 wt% DMF concentration in the feed.
    Advances in Chemical Engineering and Science 09/2011; 1(04):305-312. DOI:10.4236/aces.2011.14042
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    • "As the amount of DMF utilization has increased, its potential toxic effects have also gained attention. During the last decades, several toxification cases have been reported in work places that deal with DMF [7-11]. The most prevalent disorders found in the workers exposed to DMF were liver toxicities, including hepatitis, fibrosis, cirrhosis, and cancer [7-11]. "
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    ABSTRACT: N,N-Dimethylformamide (DMF) is globally used as an organic solvent in the production of synthetic leather and resins because of its low volatility, making it an attractive industrial material. Despite its excellent property as a chemical solvent, utilization of DMF is somewhat controversial nowadays due to its hazardous effects on exposed workers in work places. Many toxification cases are being reported globally and the number of cases of liver damage is still increasing in developing countries. On account of this, a series of epidemiologic surveys are being conducted to understand the degrees of liver damage caused by DMF exposure. Furthermore, many investigations have been performed to clarify the mechanism of DMF-induced liver toxicity using both human and experimental animal models. This review summarizes the current occupational cases reported on liver damage from workers exposed to DMF in industrial work places and the research results that account for DMF-induced liver failure and possible carcinogenesis. The findings reviewed here show the synergistic toxicity of DMF exposure with other toxicants, which might occur through complicated but distinct mechanisms, which may extend our knowledge for establishing risk assessments of DMF exposure in industrial work places.
    Safety and Health at Work 06/2011; 2(2):97-104. DOI:10.5491/SHAW.2011.2.2.97
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    • "A significant association was also found between chronic liver diseases and HBV carrier status and GSTT1 null genotype. Previous pathological reports from others showed multiple zonal necrosis in one worker with acute DMF exposure (Wang et al. 1991), and micro-or macrovesicular steatosis, spotty necrosis, and regeneration in other workers with acute (from less than 2 weeks to 4 months) DMF exposure, and moderately severe micro-or macrovesicular steatosis with spotty necrosis, and regeneration in workers with 10 years of DMF exposure (Redlich et al. 1988, 1990). Hepatitis B and C virus infections have been reported to be the major causes of chronic liver diseases (including liver cirrhosis, liver cancer) in Taiwan (Beasley et al. 1982, Chen et al. 1991, Yu et al. 1991 "
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    ABSTRACT: Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure (>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.
    Biomarkers 11/2005; 10(6):464-74. DOI:10.1080/13547500500333648 · 2.26 Impact Factor
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