Pelclova Daniela, Zdimal Vladimir, Kacer Petr, Fenclova Zdenka, Vlckova Stepanka, Komarc Martin, Navratil Tomas, Schwarz Jaroslav, Zikova Nadezda, Makes Otakar, Syslova Kamila, Belacek Jaroslav, Zakharov Sergey
Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojišti 1, 128 00 Prague 2, Czech Republic.
J Breath Res. 2016 Jun 30;10(3):036004. doi: 10.1088/1752-7155/10/3/036004.
Human health data regarding exposure to nanoparticles are extremely scarce and biomonitoring of exposure is lacking in spite of rodent pathological experimental data. Potential markers of the health-effects of engineered nanoparticles were examined in 30 workers exposed to TiO2 aerosol, 22 office employees of the same plant, and 45 unexposed controls. Leukotrienes (LT) B4, C4, E4, and D4 were analysed in the exhaled breath condensate (EBC) and urine via liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Fractional exhaled nitric oxide (FeNO) and spirometry was also measured. The median particle number concentration of the aerosol in the production ranged from 1.98 × 10(4) to 2.32 × 10(4) particles cm(-3); about 80% of the particles were <100 nm in diameter. Median total mass concentration varied between 0.4 and 0.65 mg m(-3). All LT levels in workers' EBC were elevated relative to the controls (p < 0.01). LTs in the EBC sample were correlated with titanium levels. Urinary LTs were not elevated in the workers and office employees. Office workers had higher LTB4 in EBC (p < 0.05), and higher levels of FeNO (p < 0.01). FeNO was higher in office employees with allergic diseases and was negatively correlated with smoking (p < 0.01). In spirometry significant impairment in the workers was seen only for %VCIN and %PEF (both p < 0.01). Multiple regression analysis confirmed a significant association between production of TiO2 and all cysteinyl LTs in EBC (p < 0.01) and impaired %VCIN and %PEF (both p < 0.01). LTB4 was also associated with smoking (p < 0.01). LT levels complemented our earlier findings of DNA, protein, and lipid damage in the EBC of workers with nanoTiO2 exposures. Cysteinyl LTs in EBC analysis suggest inflammation and potential fibrotic changes in the lungs; they may be helpful for monitoring the biological effect of (nano)TiO2 on workers. Spirometry was not sensitive enough.
尽管有啮齿动物的病理实验数据，但关于纳米颗粒暴露的人类健康数据极其稀少，且缺乏暴露生物监测。对30名接触二氧化钛气溶胶的工人、同一工厂的22名办公室员工和45名未接触者进行了工程纳米颗粒健康影响潜在标志物的检测。通过液相色谱 - 电喷雾电离 - 串联质谱法（LC - ESI - MS/MS）分析呼出气冷凝物（EBC）和尿液中的白三烯（LT）B4、C4、E4和D4。还测量了呼出一氧化氮分数（FeNO）和肺活量测定。生产过程中气溶胶原位颗粒数浓度中位数范围为1.98×10⁴至2.32×10⁴个颗粒/cm³；约80%的颗粒直径<100nm。总质量浓度中位数在0.4至0.65mg/m³之间变化。与对照组相比，工人EBC中所有LT水平均升高（p<0.01）。EBC样本中的LT与钛水平相关。工人和办公室员工尿液中的LT未升高。办公室员工EBC中的LTB4较高（p<0.05），FeNO水平也较高（p<0.01）。患有过敏性疾病的办公室员工FeNO较高，且与吸烟呈负相关（p<0.01）。在肺活量测定中，仅在工人的%VCIN和%PEF方面观察到显著损害（均p<0.01）。多元回归分析证实，二氧化钛生产与EBC中所有半胱氨酰LT之间存在显著关联（p<0.01），以及与%VCIN和%PEF受损之间存在显著关联（均p<0.01）。LTB4也与吸烟有关（p<0.01）。LT水平补充了我们早期关于纳米二氧化钛暴露工人EBC中DNA、蛋白质和脂质损伤的研究结果。EBC分析中的半胱氨酰LT提示肺部存在炎症和潜在的纤维化改变；它们可能有助于监测（纳米）二氧化钛对工人的生物学效应。肺活量测定不够敏感。
