Leukotrienes in exhaled breath condensate and fractional exhaled nitric oxide in workers exposed to TiO2 nanoparticles.

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.

Oxidative stress markers are elevated in exhaled breath condensate of workers exposed to nanoparticles during iron oxide pigment production.

Markers of oxidative stress and inflammation were analysed in the exhaled breath condensate (EBC) and urine samples of 14 workers (mean age 43 ± 7 years) exposed to iron oxide aerosol for an average of 10 ± 4 years and 14 controls (mean age 39 ± 4 years) by liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) after solid-phase extraction. Aerosol exposure in the workplace was measured by particle size spectrometers, a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS), and by aerosol concentration monitors, P-TRAK and DustTRAK DRX. Total aerosol concentrations in workplace locations varied greatly in both time and space. The median mass concentration was 0.083 mg m(-3) (IQR 0.063-0.133 mg m(-3)) and the median particle concentration was 66 800 particles cm(-3) (IQR 16,900-86,900 particles cm(-3)). In addition, more than 80% of particles were smaller than 100 nm in diameter. Markers of oxidative stress, malondialdehyde (MDA), 4-hydroxy-trans-hexenale (HHE), 4-hydroxy-trans-nonenale (HNE), 8-isoProstaglandin F2α (8-isoprostane) and aldehydes C6-C12, in addition to markers of nucleic acid oxidation, including 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-OHG), 5-hydroxymethyl uracil (5-OHMeU), and of proteins, such as o-tyrosine (o-Tyr), 3-chlorotyrosine (3-ClTyr), and 3-nitrotyrosine (3-NOTyr) were analysed in EBC and urine by LC-ESI-MS/MS. Almost all markers of lipid, nucleic acid and protein oxidation were elevated in the EBC of workers comparing with control subjects. Elevated markers were MDA, HNE, HHE, C6-C10, 8-isoprostane, 8-OHdG, 8-OHG, 5-OHMeU, 3-ClTyr, 3-NOTyr, o-Tyr (all p < 0.001), and C11 (p < 0.05). Only aldehyde C12 and the pH of samples did not differ between groups. Markers in urine were not elevated. These findings suggest the adverse effects of nano iron oxide aerosol exposure and support the utility of oxidative stress biomarkers in EBC. The analysis of urine oxidative stress biomarkers does not support the presence of systemic oxidative stress in iron oxide pigment production workers.

Raman microspectroscopy of exhaled breath condensate and urine in workers exposed to fine and nano TiO2 particles: a cross-sectional study.

The health effects of engineered nanoparticles in humans are not well-understood; however experimental data support the theory of oxidative stress promoting fibrogenesis and carcinogenicity. The aim of this study was to detect TiO2 particles in exhaled breath condensate (EBC) and urine samples to ascertain their presence and potential persistence and excretion in urine.EBC and urine samples were collected from 20 workers exposed to TiO2 aerosol; among them, 16 had a higher risk level of exposure (production workers) and four had medium risk level (research workers); in addition to 20 controls. Titanium levels in EBC and urine were analysed using the inductively coupled plasma mass spectrometry (ICP-MS) method. A Raman microspectroscopic analysis was performed in EBC and urine to identify the phase composition of TiO2 particles observed. Aerosol exposure in the workplaces was measured using SMPS and APS spectrometers and P-TRAK and DustTRAK DRX monitors.The median concentration of TiO2 aerosol was 1.98 × 10(4) particles cm(-3), the interquartile range (IQR) was 1.50 × 10(4) - 3.01 × 10(4) particles cm(-3) and the median mass concentration was 0.65 mg m(-3) (IQR 0.46-.0.83 mg m(-3)); 70-82% of the particles were smaller than 100 nm in diameter. In any part of the plant, the median TiO2 air concentration did not exceed the national airborne exposure limit of 10 mg m(-3) for inert dust. Particles of rutile and/or anatase were found in the EBC of exposed workers in 8/20 (40%) of the pre-shift and 14/20 (70%) of the post-shift samples. In the urine of workers, TiO2 particles were detected in 2/20 post-shift urine samples only. The mean concentration of titanium in the EBC in production workers was 24.1 ± 1.8 µg/l. In the research workers the values were below the limit of quantitation; LOQ = 4.0 ± 0.2 µg/l), as well as in the controls. In the urine samples of all of the subjects, titanium was under the limit of detection (LOD = 1.2 µg/l). Raman microanalysis of EBC in the workers confirmed the presence of TiO2 anatase and/or rutile crystal phases in the pre-shift samples and their persistence from previous shifts in the workers.