| Summary: | 碩士 === 國立成功大學 === 環境醫學研究所 === 92 === The exposure of the humans to the chemical mixtures is the general rule in the general environment as well as in most occupational settings. Lower toxicity or higher toxicity from mixtures than the expected depends on their constituents and potencies. It is very likely that the workers could be exposed to N,N-dimethylformamide (DMF), methyl ethyl ketone (MEK), and toluene (TOL) in the occupational environments simultaneously. This study was aimed to investigate the effects of the different co-exposure levels of MEK and toluene and different DMF on different biomarkers of DMF exposure metabolism-free form (U-DMF) and biotransformation-required forms (U-NMF, and U-AMCC), and the effects of co-exposure to DMF on urinary MEK biomarker, respectively. Twenty workers were selected from a two-stage field investigation strategy and were classified into four subgroups based on their DMF exposure and co-exposure levels. Breathing-zone air concentrations of DMF, MEK and TOL as well as dermal DMF exposure were determined for two consecutive and another five consecutive working days. The concentrations of U-DMF, U-NMF, U-AMCC and U-MEK in pre- and post-shift as well as during at least 36-hour period since the end of the exposure for each individual were analyzed. For post-shift urine measurements, we found U-DMF concentrations in high DMF subgroups were significantly higher than those in low DMF subgroups (p＜0.05). On the other hand, U-NMF and U-AMCC concentrations in high-DMF-high-coexposure subgroup were significantly lower than those in high-DMF-high-coexposure subgroup but no significant differences between two low DMF subgroups. Metabolic index (MI) showed the biotransformation from DMF to NMF, but not from NMF to AMCC, was significantly suppressed at high co-exposure (p＜0.001). We also found a significant daily accumulation of pre-shift U-NMF across five consecutive working days for those who have high co-exposure to high MEK/TOL and the day-to-day increase of U-NMF at pre-shift was approximate 1.4-fold given the occupational exposure to DMF at the same level. The lag time of excretory U-NMF for high MEK/TOL co-exposure group was significantly longer that for low co-exposure group in conventional kinetics study. The estimates of half-life, area under curve (AUC), and mean residence time (MRT) also showed the same tendency as found for lag time. For the biological monitoring of MEK part, the regression equations of A-MEK to post-shift U-MEK showed no significant differences between high and low DMF co-exposure groups. On the other hand, the estimates of the half-life and maximum concentration of post-shift U-MEK for high DMF co-exposure groups were greater than those for low DMF co-exposure groups in kinetics study. Owing to the insufficient sample sizes, this finding warranted a further study. The discrepancy between conventional kinetics approach and physiologically-based pharmacokinetics (PBPK) approach could result from the differences in races and exposure scenarios as well as insufficient sample size. We concluded that co-exposure to high MEK/TOL could result in 1. the suppression of U-NMF and U-AMCC at high DMF exposure; 2. the accumulation of U-NMF at daily pre-shift urines; 3). the increases of the lag time, half-life, MRT, and AUC for U-NMF. Difference. For the biological monitoring of MEK part, no significant effects of co-exposure to DMF on post-shift U-MEK. Some effects might exist in the estimates of the kinetic parameters and this warranted a further study to confirm. Due to the ubiquity of co-existence of MEK, TOL and DMF in occupational settings, biological monitoring for the above-mentioned chemicals should be carefully evaluated while the co-exposure is substantial and a more comprehensive longitudinal health evaluation program should be performed for those workers.
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