Toxic Hepatitis Induced by Occupational Dimethylacetamide Exposure

Choi, Tae Sung; Woo, Kuck Hyeun; Kim, Jin Seok; Park, Wan Seup; Ham, Jung Ho; Jung, Sang Je; Yu, Jae-Ho

doi:10.35371/kjoem.2001.13.2.164

Cited by 8 publications

(10 citation statements)

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“…We hypothesize that this change in clinical presentation of serious, life-threatening VOD/SOS may be due to an interaction between DMA and Bu in the generation of liver toxicity, because oral Bu-(Cy) associated VOD historically manifested itself quickly, within the rst few weeks after drug exposure. This delayed onset of serious liver toxicity after 8-12 weeks of exposure is somewhat reminiscent of what was described by Choi et al after occupational exposure to DMA, [15].…”

Section: Discussionsupporting

confidence: 76%

“…A DMA-based solvent system was at the time felt by the sponsor to be safe, primarily based on a published trial using DMA as an anticancer agent in its own right [14]. However, in the review of the phase II data underlying the regulatory approval of IV Bu, Busulfex, the FDA expert examiner expressed concern about DMA; he surmised that the total amount of DMA given in high-dose chemotherapy may be enough to cause signi cant toxicities [1], because occupational DMA exposure has been associated with both neurological and hepatic toxicity, and in experimental systems it has been shown to cause reproductive toxicity [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy

Ramdial

Chan

Petitto

et al. 2023

Bone Marrow Transplant

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Intravenous Busulfan-based (IV Bu-) conditioning regimens are widely used in stem cell transplant and have been demonstrated as more effective and safer than cyclophosphamide and total body irradiation. Despite its superiority concerns remain regarding toxicities, speci cally, veno-occlusive disease/sinusoidal obstructive syndrome, reproductive toxicity and neurotoxicity. Some of these concerns do not relate to busulfan itself, but to its composite solvent vehicle including N,N-dimethylacetamide (DMA). Herein, we report a case series of six patients who received high-dose IV Bubased conditioning regimens, and who developed neurotoxicity with various neurological manifestations and outcomes, ranging from mild to fatal. This case series highlights the need for further studies to investigate the safety of IV Bu, especially in patients with an underlying organic brain disorder, who have been treated with immunoconjugates with a potential for central neurotoxicity, or who have received therapeutic brain irradiation.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy

Ramdial

Chan

Petitto

et al. 2023

Bone Marrow Transplant

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“…Table 2 summarizes the occupational liver diseases reported in the Annals of Occupational and Environmental Medicine until recently. 8 9 13 14 15 16 17 18 Cases of toxic hepatitis caused by various xlink:types of organic solvents were reported in Korea, and there were 2 cases of toxic hepatitis caused by chloroform. The first reported case was suspected chloroform-induced hepatotoxicity in a laboratory engineer in 2012, 8 and the second case was hepatotoxicity of the 2 patients who worked in the clean room at a medical endoscopic manufacturer in 2014.…”

Section: Discussionmentioning

confidence: 99%

A case report of toxic hepatitis caused by chloroform in automotive parts manufacturer coating process

Hwang

Kim

2022

Ann Occup Environ Med

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Background Several cases of chloroform-induced hepatotoxicity have been reported worldwide, but only 2 cases have been reported in Korea. We encountered a case of toxic hepatitis due to chloroform exposure in February 2022 and report the diagnosis process and clinical findings. Case presentation A 38-year-old employee in charge of the coating after washing (degreasing) at an automotive parts manufacturer complained of jaundice and was diagnosed with acute toxic hepatitis. After the initial diagnosis, he continued to work, his symptoms worsened, and he was hospitalized for 8 days. Liver ultrasonography (elastography) revealed acute hepatitis. The washing agent contained chloroform, which was not listed on the materials safety data sheet, and the concentrations of chloroform in the workplace were up to 4.7 times the time-weighted average. Conclusions This patient showed typical toxic hepatitis with chloroform; further follow-up studies are required. Both employers and workers should be aware of information on toxic substances and take precautions to avoid exposure.

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“…DMAc and DMF, both solvents that can potentially cause acute toxic hepatitis (Baum and Suruda 1997; Choi et al 2001; Kang et al 1991; Kim et al 1991; Marino et al 1994; Spies et al 1995), were detected in the environmental samples; such common solvents, which are used by many of the client industries of this plant, are likely to be the causative agents of this outbreak. Carbon tetrachloride is one of the strongest chemicals that can induce toxic hepatitis while showing hepatocellular necrosis with fatty change, but the clinical and pathologic characteristics we found do not correspond exactly with this agent, and it was not detected in our environmental samples.…”

Section: Discussionmentioning

confidence: 99%

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

Cheong

Kim

Choi

et al. 2007

Environ Health Perspect

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ContextIndustrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers.Case presentationFive workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis.DiscussionInfectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction–type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them.Relevance to clinical or professional practiceIn the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers’ health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent.

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Toxic Hepatitis Induced by Occupational Dimethylacetamide Exposure

Cited by 8 publications

References 0 publications

Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy

Intravenous Busulfan, Dimethylacetamide and neurotoxicity after high-dose pretransplant conditioning chemotherapy

A case report of toxic hepatitis caused by chloroform in automotive parts manufacturer coating process

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

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