Chronic upper airway inflammation and systemic oxidative stress from nanoparticles in photocopier operators: Mechanistic insights

Abstract

Background: Several recent studies have linked emissions from printing equipment with upper airway inflammation and systemic oxidative stress in healthy humans, lung inflammation in mice, and cytotoxicity, induction of inflammatory markers and epigenetic changes in human cell lines. Acute exposures have lead to upper airway inflammation and systemic oxidative stress, which for certain markers took longer than 24-36 h post-exposure to clear. Objective: In this follow-up work, we determined: i) whether chronic exposures to nanoparticles from copiers lead to chronic upper airway inflammation and systemic oxidative stress; and ii) whether expression patterns of biomarkers for such stresses change during transition from acute to chronic exposures. Methods: Six permanent employees from three copy centers and eleven controls participated in the study. Nasal lavage and urine samples were collected on Monday morning (pre-shift, Mo-AM) and evening (post-shift, Mo-PM), as well as at the end of the workweek (Fr-PM), over three random weeks. The matched controls were sampled over one week. Nasal lavage samples were analyzed for a panel of 14 pro-inflammatory cytokines/chemokines, inflammatory cells, and total protein. Urine samples were analyzed for 8-OH-dG, a biomarker of systemic oxidative stress. Detailed quantitative exposure assessment to airborne nanoparticles was conducted for a whole week, and included size distribution, size-fractionated aerosol collection, extensive chemical analysis, and lung burden estimates. Results:The daily geometric mean total particle number concentration varied between 14,600-21,860 particles/cm 3 , 1.7-12.1 times greater than background, with maxima up to 143,000 particles/cm 3 . Mass concentration of the nanoscale fraction was in the 1-10 µg/m 3 range.Chemical composition of the nanoparticle fraction was comprised mostly of organic compounds, mixed with several engineered nanoparticles, which contributed a metal content ranging from 2-8% of the total particulate mass.Five out of the 14 inflammatory cytokines, namely IL-6, IL-8, TNFα, IL-1β and Eotaxin, were significantly elevated in the nasal lavage samples of the chronically exposed copier operators (p < 0.0001) relative to controls. One cytokine, G-CSF, was significantly down regulated (p < 0.0001) in copier operators (p <0.05). The level of all six cytokines did not change significantly across days (i.e. Mo-AM vs. Mo-PM, and Mo-AM vs. Fr-PM) and across weeks in chronically exposed individuals. In addition, there were significant (p < 0.0001) increases in inflammatory cell infiltration (2.7 fold) in nasal lavage samples and 8-OH-dG in (4.3 fold) in urine samples. Conclusion:Chronic upper airway inflammation and systemic oxidative stress were documented in photocopier operators chronically exposed to nanoparticles. These findings agree with the recent toxicological literature on printer-emitted particles and medical case reports, and call for an industry-wide study of the health effects resulting from exposure to printer-emitted particles...

Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

“…Persistent ROS generation has been mechanistically linked to chronic inflammation and tissue injury and is one of the most studied mechanisms of ENMs toxicity. [54,55] Here, at 1 µg mL −1 of administered GO concentration, there was no effect on ROS production. On the contrary, both smGO and mGO at 5 µg mL −1 of administered concentration caused a statistically significant 1.2-fold increase in ROS production over the blank FFM, respectively (p < 0.05).…”

Deep Airway Inflammation and Respiratory Disorders in Nanocomposite Workers

“…In responses to acute exposures, these biomarkers tend to go up with other pro-inflammatory markers and then go down, as the inflammation is resolved. In chronic exposures with established inflammation, the anti-inflammatory biomarkers, such as IL 10, are not playing an important role, presumably because the feedback loops that require them are no longer functional [ 38 , 39 ]. In this study, LXB4 and IL 10 were lower in the pre-shift samples, compared with controls, which may reflect a reduced response due to long-term exposures.…”

“…Our findings are consistent with limited epidemiological studies in nanomanufacturing workers, in which reduction of lung function parameters and an increase of TNF or oxidative stress markers were described [ 15 , 43 , 44 ]. In copier operators, exposed predominantly to a mixed-type exposure to copier emitted nanoparticles that contain a few percent (1–8%) metal oxides, respiratory, immunological, cardiovascular, and other disorders may develop following nanoparticle inhalation [ 38 , 39 , 45 ]. A decade into nanomanufacturing, we are now starting to see the emergence of disease in these workers, especially respiratory airway disorders.…”

Review of the characteristics and possible health effects of particles emitted from laser printing devices

“…78 The published findings for persons who spend time in copy centers or offices with printers are manifold. They range from oxidative stress and inflammatory reactions 84,85 to sick building syndrome (SBS) 86 and on to chronic fatigue syndrome (CFS). 87 It should be noted that the work of Jaakkola et al 86 A whole series of studies address the exposure of persons in photocopy centers and printing rooms.…”

“…87 It should be noted that the work of Jaakkola et al 86 A whole series of studies address the exposure of persons in photocopy centers and printing rooms. 58,81,84,85,[90][91][92] In some studies, an attempt is made to bridge the gap between particle exposure and the chemical composition of the toner. 24,93,94 The measurement results themselves should not be questioned; however, the attribution of observations to printer emissions as compared to other possible influences may be questioned.…”