Skip navigation

Reference A comparative benchmark dose study for N, N-dimethylformamide induced liver injury in a Chinese occupational cohort.

Authors Wu Z, Liu Q, Wang C, Xu B, Guan M, Ye M, Jiang H, Zheng M, Zhang M, Zhao W, Jiang X, Leng S, Cheng J.
Institution The Toxicology Laboratory of National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, 100050, China.
Citation Toxicol Sci. 2017 May 15.
DOI ID 10.1093/toxsci/kfx076
PubMed® ID 28505332
Review Status Is curated Curated.
Abstract Widespread contamination of N,N-dimethylformamide (DMF) has been identified in the environment of leather industries and their surrounding residential areas. Few studies have assessed the dose-response relationships between internal exposure biomarkers and liver injury in DMF exposed populations. We assessed urinary N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC) and blood N-methylcarbmoylated hemoglobin (NMHb) levels in 698 Chinese DMF-exposed workers and 188 Non-DMF- exposed workers using ultra-performance liquid-chromatography tandem mass-spectrometry. Liver injury was defined as having abnormal serum activities of any of the three liver enzymes, including alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase. Higher liver injury rates were identified in DMF-exposed workers versus Non-DMF-exposed workers (9.17% vs. 4.26%, P=0.029) and in male versus female workers (11.4% vs. 3.2%, P<0.001). Positive correlations between environmental exposure categories and internal biomarker levels were identified with all three biomarkers undetectable in Non-DMF-exposed workers. Lower confidence limit of benchmark dose (BMDL) was estimated using the benchmark dose (BMD) method. Within all study subjects, BMDLs of 14.0 mg/L for NMF, 155 mg/L for AMCC, and 93.3 nmol/g for NMHb were estimated based on dose-response relationships between internal levels and liver injury rates. Among male workers, BMDLs of 10.9 mg/L for NMF, 119 mg/L for AMCC, and 97.0 nmol/g for NMHb were estimated. In conclusion, NMF, AMCC and NMHb are specific and reliable biomarkers and correlate well with DMF-induced hepatotoxicity. NMF correlates the best with liver injury, while NMHb may be the most stable indicator. Males have a greater risk of liver injury than females upon DMF exposure.