Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model

Sisler, Jennifer D.; Pirela, Sandra V.; Friend, Sherri; Farcas, Mariana T.; Schwegler‐Berry, Diane; Shvedova, Anna A.; Castranova, Vincent; Demokritou, Philip; Qian, Yong

doi:10.3109/17435390.2014.976603

Cited by 47 publications

(49 citation statements)

References 67 publications

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“…inhalation, dermal, ingestion) and specific types of effects being investigated. For example, common immortal cell lines used for investigating possible effects of inhalation exposure include Human Small Airway Epithelial cells (SAECs), Human Microvascular Endothelial Cells (HMECs), and human THP-1 macrophages 26,55,60,82 . However, it is worth noting that the proposed methodology and protocols are independent of cell type and cellular assays.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

et al. 2017

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Summary Evidence continues to grow of the importance of in vitro and in vivo dosimetry in the hazard assessment and ranking of engineered nanomaterials (ENMs). Accurate dose metrics are particularly important for in vitro cellular screening to assess the potential health risks or bioactivity of ENMs. In order to ensure meaningful and reproducible quantification of in vitro dose, with consistent measurement and reporting between laboratories, it is necessary to adopt standardized and integrated methodologies for 1) generation of stable ENM suspensions in cell culture media, 2) colloidal characterization of suspended ENMs, particularly properties that determine particle kinetics in an in vitro system (size distribution and formed agglomerate effective density), and 3) robust numerical fate and transport modeling for accurate determination of ENM dose delivered to cells over the course of the in vitro exposure. Here we present such an integrated comprehensive protocol based on such a methodology for in vitro dosimetry, including detailed standardized procedures for each of these three critical steps. The entire protocol requires approximately 6-12 hours to complete.

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Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

et al. 2017

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“…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). …”

Section: Introductionmentioning

confidence: 99%

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

Watson-Wright¹,

Singh²,

Demokritou³

2017

NanoImpact

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Nano-enabled thermoplastics are part of the growing market of nano-enabled products (NEPs) that have vast utility in several industries and consumer goods. The use and disposal of NEPs at their end of life has raised concerns about the potential release of constituent engineered nanomaterials (ENMs) during thermal decomposition and their impact on environmental health and safety. To investigate this issue, industrially relevant nano-enabled thermoplastics including polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1 and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v), and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with their pure thermoplastic matrices were thermally decomposed using the recently developed lab based Integrated Exposure Generation System (INEXS). The life cycle released particulate matter (called LCPM) was monitored using real time instrumentation, size fractionated, sampled, extracted and prepared for toxicological analysis using primary small airway epithelial cells to assess potential toxicological effects. Various cellular assays were used to assess reactive oxygen species and total glutathione as measurements of oxidative stress along with mitochondrial function, cellular viability, and DNA damage. By comparing toxicological profiles of LCPM released from polymer only (control) with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were determined. We observed associations between NEP properties such as the percent nanofiller loading, host matrix, and nanofiller chemical composition and the physico-chemical properties of released LCPM, which were linked to biological outcomes. More specifically, an increase in percent nanofiller loading promoted a toxicological response independent of increasing LCPM dose. Importantly, differences in host matrix and nanofiller composition were shown to enhance biological activity and toxicity of LCPM. This work highlights the importance of assessing the toxicological properties of LCPM and raises environmental health and safety concerns of nano-enabled products at their end of life during thermal decomposition/incineration.

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“…In a series of recently published papers, several physiologically relevant cell lines (i.e., human small airway epithelial cells, microvascular endothelial cells, macrophages and lymphoblasts) were treated with various doses of PEPs using both mono- and co-culture exposure systems (Sisler et al, 2014; Pirela et al, 2015). In both studies, it was shown that PEPs triggered an unfavorable series of biological responses in macrophages, small airway epithelial cells and microvascular endothelial cells at doses comparable to approximately 8 h or more of consumer inhalation of PEPs.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we sought to further expand on the latest cellular toxicology studies performed by our group on PEPs (Sisler et al, 2014; Pirela et al, 2015; Lu et al, 2015b). Particularly, we present findings on the murine responses to intratracheal instillation exposures to various doses of PEPs.…”

Section: Introductionmentioning

confidence: 99%

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

Pirela

Miousse

et al. 2016

NanoImpact

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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.

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Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model

Cited by 47 publications

References 67 publications

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

Preparation, characterization, and in vitro dosimetry of dispersed, engineered nanomaterials

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

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

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