title: Leukotrienes in exhaled breath condensate and fractional exhaled nitric oxide in workers exposed to TiO2 nanoparticles.
abstract: 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.
authors.affiliation: 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.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pelclova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Zdimal
authors.forename: Petr
authors.initials: P
authors.lastname: Kacer
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Fenclova
authors.forename: Stepanka
authors.initials: S
authors.lastname: Vlckova
authors.forename: Martin
authors.initials: M
authors.lastname: Komarc
authors.forename: Tomas
authors.initials: T
authors.lastname: Navratil
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Schwarz
authors.forename: Nadezda
authors.initials: N
authors.lastname: Zikova
authors.forename: Otakar
authors.initials: O
authors.lastname: Makes
authors.forename: Kamila
authors.initials: K
authors.lastname: Syslova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Belacek
authors.forename: Sergey
authors.initials: S
authors.lastname: Zakharov
mesh_terms: D000328:Adult; D000336:Aerosols / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods*; D016022:Case-Control Studies; D045853:Exhalation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015289:Leukotrienes / Q000032:analysis* / Q000652:urine; D053758:Nanoparticles / Q000009:adverse effects*; D009569:Nitric Oxide / Q000032:analysis*; D016273:Occupational Exposure / Q000032:analysis*; D012044:Regression Analysis; D012129:Respiratory Function Tests; D053719:Tandem Mass Spectrometry; D014025:Titanium / Q000009:adverse effects*; D017132:Workplace
chemical_list: D000336:Aerosols; D015415:Biomarkers; D015289:Leukotrienes; C009495:titanium dioxide; D009569:Nitric Oxide; D014025:Titanium