Occupational Exposure to N,N-Dimethylformamide and Hepatotoxicity among Synthetic Leather Workers in Bangladesh: Implications for Workplace Health and Labour Law Compliance
Year: 2026
Type: preprint
Abstract: Purpose : N,N-dimethylformamide (DMF) is a polar aprotic solvent that is extensively used in the production of synthetic leather, polyurethane products, resins, adhesives and surface coatings. Potential sources of occupational exposures are mixing, formulation, coating, solvent transfer, cleaning, maintenance, and spill-response. DMF may be inhaled and absorbed through intact skin, which means that total internal dose for a particular worker may be underestimated by only measuring DMF in the air. Liver is a known target organ of DMF toxicity, and reports of increased liver enzymes and, less frequently, clinically significant liver injury have been reported in workers occupationally exposed to DMF. Increases in liver-function tests, however, are non-specific and can occur in people who drink too much alcohol and/or are obese, and/or may be caused by metabolic disease associated with steatotic liver disease, viral hepatitis, certain medicines (prescribed or not) or other exposures that may occur at work. Therefore, a comprehensive evaluation of possible liver damage from DMF should include exposure history, workplace monitoring, biological monitoring, repeated clinical evaluations, and the careful consideration of other causes of liver damage. Objective : The aim of this study is to find the relationship between DMF exposure and liver injury in the workers working in the synthetic leather, polyurethane, resin and surface-coating industries. It will consider exposure by inhalation and skin contact, estimate internal exposure as measured by urinary markers, review liver-function patterns as they change over time, determine if another source of liver injury or exposure may have occurred, and determine if a failure of workplace controls or medical surveillance could have led to exposure. The results will help to inform evidence-based occupational-health and medico-legal decisions about the possibility and level of occupational contribution to liver disease. Methods : An occupational-health study using a mixed-methods approach will be conducted with workers who may be at risk for DMF, such as mixers, formulators, coating operators, solvent-transfer workers, cleaners, maintenance workers, and waste-handling workers. A standardised occupational history will document job titles, length of employment, work patterns, frequency of tasks, use of DMF containing products, past chemical exposures, spillages, symptoms, hygiene practices and use and suitability of personal protective equipment (PPE). Task specific workplace exposure assessments will be carried out and personal air sampling will be used, wherever possible, especially during transfer, mixing, coating, cleaning and maintenance activities. The results of the air-monitoring will be evaluated against relevant occupational exposure concentrations with an understanding that an exposure below the airborne concentration limit does not mean there is no significant dermal absorption. The dermal exposure potential will be evaluated by conducting facility observations and interviews with workers, which will include direct hands-on contact with the material, use of contaminated gloves and clothing, gloves used, gloves replaced, local exhaust ventilation, housekeeping, spill control, washing facility, training, and working practices. The urinary concentrations of N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) will be measured for internal DMF exposure. These are markers of systemic exposure from all routes of exposure including inhalation and skin contact. Ideally, urine samples will be collected at the end of shift and end of work week, or at other suitable times depending on the toxicokinetic properties of the biomarker. Urine dilutions, e.g. creatinine, specific gravity etc., will be corrected and results interpreted taking into account the timing of the sample, the analytical procedure and available biological guidance values. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) levels, bilirubin, albumin and international normalised ratio (INR) will be measured at regular intervals. These tests will assist in the identification of hepatocellular, cholestatic or mixed liver injury patterns and be useful in identifying transient, persistent or progressive liver injuries. Symptoms such as fatigue, nausea, abdominal discomfort, jaundice, pruritus and constitutional symptoms will also be recorded. Systematic assessment of potential confounding factors and alternative diagnosis. Alcohol intake, BMI, presence of diabetes, metabolic disease, pre-existing liver disease, other hepatotoxic chemicals and drug or supplement use will be recorded. Investigations may consist of a hepatology specialist review, abdominal ultrasound and hepatitis B and C testing, where clinically appropriate and consented to. There will be a structured medico-legal review, combining evidence from 4 domains – exposure, biological plausibility, individual clinical disease and duty of care. Occupational history and occupational monitoring will support the results of urinary biomarkers as evidence of internal exposure. The adequacy of engineering controls, local exhaust ventilation, training, spill management, hazard communication and medical surveillance will be taken into account in the duty of care assessment. Challenging with the drug after a possible hepatotoxic reaction will not take place. Expected Results : The study will not pre-judge causation as there is currently no data. It is anticipated to see if the workers with high overall or task specific exposure would have higher levels of urinary NMF and AMCC, and if these workers would have more frequent and persistent liver-test abnormalities. It will also be evaluated if liver enzymes improve if DMF exposure is reduced or eliminated, if follow up is available. Importantly, the analysis will differentiate isolated elevations of enzymes from a pattern of occupationally related disease. Conclusions :Concurring inhalational and dermal exposure to DMF is an occupational-health hazard that can be prevented. Task-based exposure assessment, urinary biomarkers, serial liver tests, clinical differential diagnosis and structured medico-legal analysis is a better approach for assessing possible occupational hepatotoxicity than liver enzymes alone. Decisions regarding the possibility, probability and highly probable occupational contribution will be based on the overall evidence and distinct from legal liability.PPE, training, spillage or medical surveillance had a significant impact on the workers.
Source: Research Square
Authors: Ahad Uddin Meazi, Sheikh Nasiba Ema
Institution: Daffodil International University
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225801358
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