Biomarkers of oxidative stress in urine and plasma of operators at six Singapore printing centers and their association with several metrics of printer-emitted nanoparticle exposures

Abstract

Inhalation of nanoparticles emitted from toner-based printing equipment (TPE), such as laser printers and photocopiers, also known as PEPs, has been associated with systemic inflammation, hypertension, cardiovascular disease, respiratory disorders, and genotoxicity. Global serum metabolomics analysis in 19 healthy TPE operators found 52 dysregulated biomolecules involved in upregulation of inflammation, immune, and antioxidant responses and downregulation of cellular energetics and cell proliferation. Here, we build on the metabolomics study by investigating the association of a panel of nine urinary OS biomarkers reflecting DNA/RNA damage (8OHdG, 8OHG, and 5OHMeU), protein/amino acid oxidation (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine), and lipid oxidation (8-isoprostane, 4-hydroxy nonenal, and malondialdehyde [MDA]), as well as plasma total MDA and total protein carbonyl (TPC), with several nanoparticle exposure metrics in the same 19 healthy TPE operators. Plasma total MDA, urinary 5OHMeU, 3-chlorotyrosine, and 3-nitrotyrosine were positively, whereas o-tyrosine inversely and statistically significantly associated with PEPs exposure in multivariate models, after adjusting for age and urinary creatinine. Urinary 8OHdG, 8OHG, 5OHMeU, and total MDA in urine and plasma had group mean values higher than expected in healthy controls without PEPs exposure and comparable to those of workers experiencing low to moderate levels of oxidative stress (OS). The highest exposure group had OS biomarker values, most notably 8OHdG, 8OHG, and total MDA, that compared to workers exposed to welding fumes and titanium dioxide. Particle number concentration was the most sensitive and robust exposure metric. A combination of nanoparticle number concentration and OS potential of fresh aerosols is recommended for larger scale future studies.

Keywords:

• Laser printers and photocopiers
• engineered nanoparticles
• urine
• plasma
• oxidative stress
• DNA damage
• 8OHdG
• isoprostane
• malondialdehyde
• total protein carbonyl

Acknowledgments

The authors thank Dr Poh Tuang Yeow for his role in study co-ordination and specimen collection and all the workers and supervisors of copy centers for their support of this study. The authors thank Dr. Yipei Zhang for his assistance with the initial LC-MS/MS method development, validation, and knowledge transfer, Suresh Bandhari for his assistance with the analysis of MDA and TPC, as well as Paridhiben Patel for her assistance with Figure 3. The authors also thank the team from IOM Singapore (Sriram P.R. Krishnan, Xian Huang, Michael Riediker, and Robert J. Aitken) for their technical support in carrying out the field exposure measurements.

Ethics approval and consent to participate

All study recruitment and sampling procedures were approved by the institutional review board of Nanyang Technological University, Singapore (Ref: IRB-2017-07-023). Each participant was explained the purpose of the study and involved procedures and was then asked to sign an informed consent.

Consent for publication

All authors have agreed with and approved the content of the manuscript.

Author contributions

The manuscript was produced and written through contributions from all authors. All authors have given approval to the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability of data and materials

Data supporting the findings are found within the manuscript and supplemental material. Raw data files will be provided by the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the Nanyang Technological University − Harvard School of Public Health Initiative for Sustainable Nanotechnology [NTU-Harvard SusNano; ref No. NTU-HSPH 17001]. LC was supported in part through DB’s research investment funds.