title: Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide.
abstract: The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: C A
authors.initials: CA
authors.lastname: Redlich
authors.forename: A B
authors.initials: AB
authors.lastname: West
authors.forename: L
authors.initials: L
authors.lastname: Fleming
authors.forename: L D
authors.initials: LD
authors.lastname: True
authors.forename: M R
authors.initials: MR
authors.lastname: Cullen
authors.forename: C A
authors.initials: CA
authors.lastname: Riely
mesh_terms: D000328:Adult; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004126:Dimethylformamide / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007728:Kupffer Cells / Q000473:pathology; D008111:Liver Function Tests; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D010150:Paint / Q000009:adverse effects; D011140:Polyurethanes; D013783:Textile Industry; D000637:Transaminases / Q000378:metabolism
chemical_list: D011140:Polyurethanes; D004126:Dimethylformamide; D000637:Transaminases