Elsevier

NanoImpact

Volume 21, January 2021, 100292
NanoImpact

Quantifying respiratory tract deposition of airborne graphene nanoplatelets: The impact of plate-like shape and folded structure

https://doi.org/10.1016/j.impact.2021.100292Get rights and content

Highlights

  • Respirable aerodynamic diameter enabled GNPs deposition in human respiratory tract.

  • Plate-like shape and folded structure of GNPs affected lung deposition fractions.

  • Most of small GNPs deposited in alveolar region, while large GNPs deposited in head airways.

  • Folded GNPs had higher alveolar deposition than planar GNPs.

Abstract

The booming development of commercial products containing graphene nanoplatelets (GNPs) triggers growing concerns over their release into the air. Precise prediction of human respiratory system deposition of airborne GNPs, especially in alveolar region, is very important for inhalation exposure assessment. In this study, the pulmonary deposition of airborne GNPs was predicted by the multiple-path particle dosimetry (MPPD) model with consideration of GNPs plate-like shape and folded structure effect. Different equivalent diameters of GNPs were derived and utilized to describe different deposition mechanisms in the MPPD model. Both of small GNPs (geometric lateral size dg < 0.1 μm) and large GNPs (dg > 10 μm) had high deposition fractions in human respiratory system. The total deposition fractions for 0.1 and 30 μm GNPs were 41.6% and 75.6%, respectively. Most of the small GNPs deposited in the alveolar region, while the large GNPs deposited in the head airways. The aerodynamic diameter of GNPs was much smaller than the geometric lateral dimension due to the nanoscale thickness. For GNPs with geometric lateral size of 30 μm, the aerodynamic diameter was 2.98 μm. The small aerodynamic diameter of plate-like GNPs enabled deposition in the alveolar region, and folded GNPs had higher alveolar deposition than planar GNPs. Heavy breathing led to higher GNPs deposition fraction in head airways and lower deposition fractions in the alveolar region than resting breathing.

Introduction

Graphene nanoplatelets (GNPs) are two-dimensional nanoparticles made from graphite with typical lateral dimension of 0.5–20 μm and 0.34–100 nm in thickness. Two-dimensional GNPs exhibit superior mechanical strength (Anwar et al., 2015), excellent electrical conductivity (Kashi et al., 2018) and higher thermal conductivity (Soldano et al., 2010) compared to zero-dimensional fullerenes and one-dimensional nanotubes. GNPs have been widely used in electronics (Sun et al., 2011), sensors (He et al., 2012), composite materials (Idowu et al., 2018), energy storage (Allahbakhsh and Arjmand, 2019) and biotechnology (Kurapati et al., 2016), and the global market of graphene is predicted to reach $311.2 million by 2022 (Zhang et al., 2018). Due to the fact that some GNPs are inevitably released into the environment during product manufacturing, use and disposal processes, the concern about their potential impact on environment and human health has been growing (Pelin et al., 2018; Zhang et al., 2019; Gao et al., 2020; Netkueakul et al., 2020; Fadeel et al., 2018; Park et al., 2017). Released GNPs in the airborne form are especially troubling due to their high mobility and the possibility of entering human body. Inhalation uptake is the most critical exposure route compared to other pathways, such as dermal adsorption and ingestion. The National Institute for Occupational Safety and Health (NIOSH) published a research about engineering control for nanoscale graphene platelets during manufacturing and handling processes in 2011 (Lo et al., 2011). According to this report, airborne graphene platelets with number concentration higher than 2 × 106 cm−3 were found in the production areas. Compared with spherical particles with the same volume, GNPs have larger lateral dimensions owing to the plate-like shape. Attempted uptake of GNPs by macrophages could lead to frustrated phagocytosis and result in inflammation (Sanchez et al., 2012; Schinwald et al., 2012). Therefore, precise prediction of respiratory deposition of airborne GNPs is very important for human exposure risk assessment.

The shape of a particle is an important factor which influences the particle aerodynamic properties. The GNPs exhibit unique aerodynamics owing to the platelet morphology, nevertheless, studies about the plate-like shape impact on GNPs lung deposition are scarce. There are some researches on inhalation exposure of fiber-like shaped particles, such as carbon nanotubes (CNTs; Sturm, 2016; Liu et al., 2019) and asbestos (Mossman et al., 2011; Bernstein et al., 2006). As fiber-like particles tend to align with the airflow when inhaled into the respiratory tract, the length and aspect ratio of the particle are very important factors. The significance of particle length in asbestos toxicity was first studied by Vorwald et al. (1951), subsequently the inflammatory response of fiber-like particles was confirmed by many studies (Donaldson et al., 2006; Donaldson et al., 2010). However, up till now, researches on the inhalation exposure of two-dimensional GNPs are far from adequate and how the plate-like structure affects the respiratory deposition is not clear.

Because of the large lateral dimension to thickness ratio and out-of-plane flexibility, GNPs are easily warped in the out-of-plane direction. This unique property and van der Waals attraction between graphene sheets facilitate the self-folded configuration (Li et al., 2018a). The study about folding could be traced back to the 1990s, where folding was observed due to the friction between scanning probe microscopy tips and the surface of pyrolytic graphite. The mechanical stimulation overcomes the potential barriers for deformation and triggers self-folding, and the van der Waals attraction determines the stability of the self-folded pattern (Zhang et al., 2010). Recently, self-folding behavior of GNPs has been studied by more and more researchers. Cranford et al. (2009) utilized an atomistic model to simulate the self-folding of graphene sheets and derived the critical self-folding length. Meng et al. (2013) proposed a theoretical model based on finite deformation beam theory to predict the self-folding of graphene, and the theoretical model showed good agreement with molecular dynamics simulation. Folding converts GNPs into more complex shapes and affects GNPs transport dynamics during respiratory deposition. Therefore, it is important to take folding into consideration for more accurate lung deposition prediction of airborne GNPs.

The potential health impact of GNPs inhalation exposure has attracted substantial interest. The toxicity of graphene-related materials depends on the physicochemical properties including exposure dose (Mullick Chowdhury et al., 2013), lateral dimension (Zhang et al., 2013), surface structure (Li et al., 2018b), functional groups (Sasidharan et al., 2011), as well as dispersion state (Duch et al., 2011). The hazard of inhaled particles also depends on their deposition site in the respiratory tract. Compared to particles in the bronchus which can be eliminated from sputum, particles in the alveolar are engulfed by the macrophages and cleared over several months, which makes them more harmful to human health (Ou et al., 2016). Two experimental methods have been used to study the respiratory tract deposition of graphene-related materials. One is animal experiments with radioisotope tracing (Li et al., 2013). Another is experiments based on human airways replicate casts (Su et al., 2016). Animal exposure experiments including intratracheal instillation (Duch et al., 2011), pharyngeal aspiration (Schinwald et al., 2012), and inhalation exposure (Ma-Hock et al., 2013) were reported. Intratracheal instillation in mice resulted in pulmonary edema and dose-dependent acute lung inflammation, and 47% GNPs still in the lung after 4 weeks (Mao et al., 2016). Animal exposure experiments were useful to study the total lung deposition. Human airways cast experiments gave more information about the regional deposition, but still limited to the evaluation of particle deposition in large bronchial airway, with less accuracy for small airways such as alveolar region. Lung deposition model provides an effective way to give more information about small airway deposition. The International Commission on Radiological Protection (ICRP) model, multiple-path particle dosimetry (MPPD) model, and computational fluid dynamics (CFD) model have been developed for simulating particle pulmonary deposition. In the ICRP model, aerosol deposition was estimated by semi-empirical expressions based on experimental data, and the accuracy of ICRP model should be improved (Guha et al., 2014). The CFD models simulated fluid physics based on the 3D sections of respiratory tract. As there were no accurate morphometric data for lower airways, the CFD model was limited to predict particle deposition in upper airways (Sandeau et al., 2010). The MPPD model was established based on actual lung morphology, and predicted both total and regional deposition. Anjilvel and Asgharian (1995) firstly introduced the multiple-path model to estimate particle deposition in the rat lung. Subsequently, this model was improved and proved to be a reliable model to evaluate particle deposition in animals and humans (Lee et al., 2019; Hammer et al., 2020). The MPPD model could simulate the deposition of non-spherical particles using particle equivalent diameters instead of geometric diameter to consider particle shape effect. There were no studies of comprehensive respiratory deposition assessment of airborne GNPs using MPPD model.

In the present work, the airborne GNPs deposition in the head airways, tracheobronchial and alveolar regions were simulated by the MPPD model. The GNPs aerodynamic diameter was derived based on the aerodynamics of oblate spheroids with random orientation. Various equivalent diameters (aerodynamic diameter, sedimentation diameter, mobility diameter) of GNPs were applied in the MPPD model to consider the plate-like shape impact on respiratory tract deposition. The folding effect was investigated by comparing the deposition fractions of planar GNPs and folded GNPs. In addition, the GNPs respiratory deposition was systematically discussed based on different breathing scenarios and respiratory parameters for comprehensive exposure assessment of airborne GNPs. Fig. 1 shows the schematic representation of the plate-like structure and respiratory deposition assessment of airborne GNPs. This study revealed the influence of plate-like shape and folded structure on GNPs transport dynamics during respiratory deposition, and emphasized the potential of GNPs accumulation in the alveolar region due to their respirable aerodynamic diameter.

Section snippets

Materials and methods

The graphene nanoplatelets (GNPs) were provided by XG Science, USA. The average geometric lateral dimension was 5 μm. The specific surface area was 120–150 m2 g−1 and the true density was 2.2 g cm−3. Airborne GNPs were produced via a Collison type atomizer by atomizing 0.02 wt% GNPs suspension. GNPs were dispersed in water and ultrasonicated for 20 min before atomizing to avoid agglomeration. Airborne GNPs were collected on Nuclepore membranes (WHA-111112, Whatman International, UK) for

Aerodynamic diameter da

The aerodynamic diameter da was significant for calculating particle deposition due to impaction mechanism. When a particle was released in air, it reached its settling velocity as the drag force offset the gravity. The drag force of plate-like GNPs was derived on basis of the drag force expressions for oblate spheroid (Lai and Mockros, 2006), which has been commonly applied for plate-like particle aerodynamics calculation in previous studies (Cheng et al., 1988a, Cheng et al., 1988b). The

Characterization of plate-like shape and folded structure of airborne GNPs

The pristine GNPs showed platelet shape with average lateral size of 5 μm (Fig. 2a). Airborne GNPs were produced by atomizing 0.02 wt% GNPs suspension and collected on Nuclepore membranes for geometric size measurement. As GNPs had irregular shape, the geometric diameter was defined as the diameter of a circle that had the same projected area as GNPs silhouette. The airborne GNPs remained the plate-like morphology (Fig. 2b), and the geometric lateral size of airborne GNPs was 0.5–3.5 μm

Discussion

In this study, the aerodynamic diameter of GNPs was derived from the aerodynamics of oblate spheroids by considering the gravitational force and aerodynamic resistance perpendicular and parallel to particle motion, and the effect of random orientation was taken into consideration. For GNPs with 30 μm geometric lateral size, the aerodynamic diameter was 2.98 μm, which was within the respiratory particle size. The calculation results in our study matched well with the results in the literature.

Conclusions

In summary, the plate-like morphology and folded structure affected the aerodynamic property and equivalent diameters of GNPs, further affecting GNPs transportation and deposition in the respiratory tract. Both of small GNPs (dg < 0.1 μm) and large GNPs (dg > 10 μm) had high total deposition fractions in human respiratory tract calculated by the MPPD model. The total deposition fractions for 0.1 μm and 30 μm GNPs were 41.6% and 75.6%, respectively. Most of the small GNPs deposited in the

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work is supported by Swiss National Science Foundation (grant number 310030_169207). The authors thank financial support from China Scholarship Council.

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