4.7 Article

Human Biomonitoring Initiative (HBM4EU): Human Biomonitoring Guidance Values Derived for Dimethylformamide

期刊

TOXICS
卷 10, 期 6, 页码 -

出版社

MDPI
DOI: 10.3390/toxics10060298

关键词

HBM4EU; dimethylformamide; DMF; HBM-GV; guidance value; biomarker; human biomonitoring; toxicokinetics; health effects; liver; carcinogenicity; reprotoxic effects

资金

  1. European Union [733032]

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The methodology to derive human biomonitoring guidance values for dimethylformamide (DMF) within the HBM4EU project was applied in this study. Hepatotoxicity of DMF was found to be the most sensitive effect, with liver enzyme concentrations serving as biomarkers. The biomarkers tNMF and AMCC in urine were selected for biological monitoring of workers exposed to DMF, with different half-lives complementing each other. Medium-high confidence levels were set for tNMF, while further investigations are needed for the consolidation of health-based HBM-GV for AMCC in urine.
Within the European Joint Program on Human Biomonitoring HBM4EU, human biomonitoring guidance values (HBM-GVs) for the general population (HBM-GV(GenPop)) or for occupationally exposed adults (HBM-GV(Worker)) are derived for prioritized substances including dimethylformamide (DMF). The methodology to derive these values that was agreed upon within the HBM4EU project was applied. A large database on DMF exposure from studies conducted at workplaces provided dose-response relationships between biomarker concentrations and health effects. The hepatotoxicity of DMF has been identified as having the most sensitive effect, with increased liver enzyme concentrations serving as biomarkers of the effect. Out of the available biomarkers of DMF exposure studied in this paper, the following were selected to derive HBM-GV(Worker): total N-methylformamide (tNMF) (sum of N-hydroxymethyl-N-methylformamide and NMF) and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine. The proposed HBM-GV(Worker) is 10 mg center dot L-1 or 10 mg center dot g(-1) creatinine for both biomarkers. Due to their different half-lives, tNMF (representative of the exposure of the day) and AMCC (representative of the preceding days' exposure) are complementary for the biological monitoring of workers exposed to DMF. The levels of confidence for these HBM-GV(Worker) are set to high for tNMF and medium-low for AMCC. Therefore, further investigations are required for the consolidation of the health-based HBM-GV for AMCC in urine.

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