The influence of airborne N,N-dimethylformamide on liver toxicity measured in industry workers: A systematic review and meta-analysis

Abstract

Background: Modern industry is developing and so is the consumption of N,N-dimethylformamide (DMF) and the occupational population exposed to DMF. However, chronic occupational and experimental exposure to DMF has been especially linked to liver and gastrointestinal disturbances. Aims: This study aims to systematically review and evaluate with a meta-analysis the influence of DMF exposure on human liver toxicity. Methods: The PubMed/Medline, the ECHA restriction dossier and the Web of Science were searched. Midpoint DMF exposure levels were calculated, and the association between DMF exposure and liver toxicity was investigated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: Of 92 screened articles, 19 articles were included in the review and of them, 10 articles were included in the meta-analysis. No association was observed when the midpoint DMF exposure was less than 20 mg/m3 (OR: 1.58, 95% CIs: 0.68–3.65). A positive association between DMF exposure and liver toxicity was observed when the midpoint DMF exposure was between 21 mg/m3 and 25 mg/m3 (OR: 3.26, 95% CIs: 1.38–7.73). Conclusions: Higher exposure DMF levels are associated with liver toxicity. However, these results tend to overestimate potential risks because the use of midpoint exposures includes and gives weight to populations at the upper end of the exposure distributions and because liver toxicity was defined as a statistical significant difference in liver enzyme levels compared to control groups, which is not identical to biologically relevant effects and adverse health effects.