Markers of lipid oxidative damage in the exhaled breath condensate of nano TiO₂production workers

Abstract

Nanoscale titanium dioxide (nanoTiO 2 ) is a commercially important nanomaterial. Animal studies have documented lung injury and inflammation, oxidative stress, cytotoxicity and genotoxicity. Yet, human health data are scarce and quantitative risk assessments and biomonitoring of exposure are lacking. NanoTiO 2 is classified by IARC as a group 2B, possible human carcinogen. In our earlier studies we documented an increase in markers of inflammation, as well as DNA and protein oxidative damage, in exhaled breath condensate (EBC) of workers exposed nanoTiO 2 . This study focuses on biomarkers of lipid oxidation. Several established lipid oxidative markers (malondialdehyde, 4-hydroxy-trans-hexenal, 4-hydroxytrans-nonenal, 8-isoProstaglandin F2a and aldehydes C 6 -C 12 ) were studied in EBC and urine of 34 workers and 45 comparable controls. The median particle number concentration in the production line ranged from 1.98 Â 10 4 to 2.32 Â 10 4 particles/cm 3 with $80% of the particles <100 nm in diameter. Mass concentration varied between 0.40 and 0.65 mg/m 3 . All 11 markers of lipid oxidation were elevated in production workers relative to the controls (p < 0.001). A significant dose-dependent association was found between exposure to TiO 2 and markers of lipid oxidation in the EBC. These markers were not elevated in the urine samples. Lipid oxidation in the EBC of workers exposed to (nano)TiO 2 complements our earlier findings on DNA and protein damage. These results are consistent with the oxidative stress hypothesis and suggest lung injury at the molecular level. Further studies should focus on clinical markers of potential disease progression. EBC has reemerged as a sensitive technique for noninvasive monitoring of workers exposed to engineered nanoparticles. ARTICLE HISTORY

Current state of knowledge on the health effects of engineered nanomaterials in workers: a systematic review of human studies and epidemiological investigations

“…In this regard, a significant increase in markers of oxidative stress damage of nucleic acids and proteins in the EBC was evident in the more exposed production workers, involved in micronation, calcination and other TiO 2 -ENM production activities, than in the lower exposed groups of research workers and controls (69). In another study, when a panel of biomarkers of lipid oxidation was investigated in the EBC of workers exposed to TiO 2 -ENM during production tasks as well as in office employees of the TiO 2 production plant, significant dose-dependent increases were detected compared to unexposed controls (70,71). In a recent investigation, occupational exposure to TiO 2 -ENM in manufacturing and/or handling facilities resulted in significantly higher oxidative biomarkers, such as urinary 8-OHdG and EBC 8-isoprostane (38).…”

“…Overall, considering the central role of the respiratory system in the toxicokinetic and toxicodynamic profile of ENM, the EBC, which needs further validation, has been proposed as a possible biological matrix to detect biomarkers of exposure, ie, the titanium content (64) and early effect, ie, alterations in pro-inflammatory, oxidative stress indicators (66, 67, 69-71, 121, 122), as well as lung damage biomarkers (SP-D) (65). Additionally, nucleic acid, and protein and lipid oxidation biomarkers have been proposed as possible indicators of the oxidative stress reactions induced by ENM in the pulmonary system that can be assessed in EBC (69)(70)(71)121). Moreover, considering that the persistence of inflammation and oxidative stress in the lungs may have a "systemic" impact on exposed organisms, biological monitoring investigations should consider biomarkers of systemic inflammatory and oxidative stress response in serum and changes in blood cell counts.…”

Safety of titanium dioxide nanoparticles in cosmetics

“…In humans, eight studies assessed nano‐TiO 2 toxicological effects on workers exposed to nano‐TiO 2 by inhalation . Results suggested possible pulmonary and cardiovascular effects.…”

“…In humans, eight studies assessed nano-TiO 2 toxicological effects on workers exposed to nano-TiO 2 by inhalation. [93][94][95][96][97][98][99][100] Results suggested possible pulmonary and cardiovascular effects. Nevertheless, no causal link between TiO 2 inhalation exposure and the observed effects could be established in these studies.…”

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate

“…Instead, urine appears as a more suitable matrix, with reduced sample manipulationno severe pre-treatment or pre-purification steps, and thus a reduced risk of pre-analytical artifacts compared to blood (Andreoli et al 2011). Therefore, the exhaled breath condensate (EBC) has been recently proposed as a noninvasively collected biological matrix to detect biomarkers of oxidative stress reflecting inflammation in the cell (Lee et al 2015;Pelclova et al 2016a;Pelclova et al 2017;Vlaanderen et al 2017;Wu et al 2014). Consequently, EBC is the preferential matrix for establishing the reference ranges for the most promising OS biomarkers for non-invasive biological surveillance of ENM-exposed workers.…”