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 male Balb/c mice 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 the Ccl5 (Rantes), Nos1 and Ucp2 genes 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.

Synergistic effects of engineered nanoparticles and organics released from laser printers using nano-enabled toners: potential health implications from exposures to the emitted organic aerosol

“…In our previous studies, it was found that human small airway epithelial cells, microvascular endothelial cells, macrophages, and lymphoblasts showed substantial changes in cell viability, production of reactive oxygen species, release of inflammatory cytokines and modifications to the DNA methylation machinery (18–20). Animal experimental models have also confirmed the findings stated previously, including upregulation of neutrophils, macrophages and changes in the expression of genes that are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens (21,22). Various epidemiological studies with detailed exposure characterization data have been done in photocopy centers.…”

Development and characterization of electronic-cigarette exposure generation system (Ecig-EGS) for the physico-chemical and toxicological assessment of electronic cigarette emissions

“…The Harvard compact cascade impactor (CCI) (Pirela et al 2016; Pal et al 2015; Pirela et al 2014; Demokritou et al 2004) was connected to e-cig mixing chamber for size-fractioned sampling. Particles were size fractionated and collected in three size fractions: PM 0.1 , PM 0.1–2.5 , PM 2.5–10 .…”

Toxicological implications of released particulate matter during thermal decomposition of nano-enabled thermoplastics

“…Nano-enabled thermoplastics or nanocomposites can contain nanofillers such as silica nanoparticles (Stojanović et al , 2013), clays (Fang et al , 2008), metal oxides (Perkgoz et al , 2011), carbon fibers (Al-Saleh et al , 2013) and carbon nanotubes (Sahoo et al , 2010) enabling extensive mechanical and electrical properties. Although, ENMs afford many useful properties, certain ENMs can cause adverse health effects such as cytotoxicity (DeLoid et al , 2016; DeLoid et al , 2014; Pirela et al , 2013; Pirela et al , 2014a), genotoxicity (Watson et al , 2013), epigenetic changes (Lu et al , 2016a; Lu et al , 2016b), and lung inflammation upon exposure (Borm et al , 2006; Konduru et al , 2014; Pirela, et al, 2013; Pirela et al , 2016). With this in mind, considerable concern over the hazards that may ensue due to the release of ENMs during consumer use and disposal of nano-enabled thermoplastics has created efforts to understand potential exposures across the life cycle of nano-enabled products (Bouillard et al , 2013; Grassian et al , 2016; Pirela et al , 2014b; Sisler et al , 2014; Wohlleben et al , 2011; Wohlleben and Neubauer, 2016).…”