title: Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use.
abstract: Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use "real world" printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old maleBalb/cmice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of theCcl5(Rantes),Nos1andUcp2genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects.
authors.affiliation: Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, T. H. Chan School of Public Health, Harvard University, Boston, MA, United States.
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Pirela
authors.affiliation: Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, T. H. Chan School of Public Health, Harvard University, Boston, MA, United States.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miousse
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, United States.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Sisler
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Pharmaceutical Sciences/Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, United States.
authors.forename: Nancy
authors.initials: N
authors.lastname: Guo
authors.affiliation: Department of Environmental and Occupational Health, College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.affiliation: Department of Pharmaceutical Sciences/Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV, United States.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: U.S. Consumer Product Safety Commission, Office of Hazard Identification and Reduction, Rockville, MD, United States.
authors.forename: Treye
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, T. H. Chan School of Public Health, Harvard University, Boston, MA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Godleski
authors.affiliation: Department of Environmental Health, Center for Nanotechnology and Nanotoxicology, T. H. Chan School of Public Health, Harvard University, Boston, MA, United States.
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
keywords: Epigenetics; Inflammation; Laser printers; Nanoparticles