Assessing inhalation intake of microplastics using MPPD model
Article information
Abstract
Increasing evidence of the presence of small microplastics in human tissues necessitates research on their intake routes and internalization. Among two major routes of exposure to microplastics (MPs), inhalation pathways are less investigated than ingestion pathways. In this study, quantitative estimation of microplastics intake and internalization was conducted using the multi-path particle dosimetry (MPPD) model by US Environmental Protection Agency assuming three representative particle size distributions (i.e., Power law, unimodal, and biomodal distributions) of cylindrical MPs within the aerodynamic diameter between 0.1 and 10 μm at the aspect ratio of 3:1. Assuming the default atmospheric concentration of MPs at 0.1 μg m–3, the estimated mass deposition in human lungs ranged 19.1–49.9 μg. Although sensitivity analysis revealed that estimated mass deposition of MPs in human lungs were not much different among three particle size distributions, deposition in the pulmonary region was strongly affected by the type of size distributions. Because of suspected health symptoms of MPs in the pulmonary region and the slower clearance in this region, it is of urgent needs to characterize MP size distribution in the inhalable particle size range (0.1–10 μm) and to analyze MPs in the same size range in human respiratory tissues.
Introduction
Microplastics (MPs) are found in almost all environmental and food media [1-6], raising concerns about human exposure to them and their related adverse health effects [7-11]. MPs have been detected in various human tissues, including the lungs [12], placenta [13], saphenous veins [14], and cirrhotic liver tissues [15]. However, the pathways through which MPs reach body tissues remain poorly understood [11,16-18].
Dietary, inhalation, and dermal uptakes are the three major pathways for the internalization of MPs from the environment and foods. Many studies have focused on the dietary uptake of MPs through analyses of MPs in food and beverages [4,19,20], as well as in human feces [21,22]. Compared with dietary exposure, inhalation and dermal exposure to MPs have been less investigated. While the penetration of MPs through the skin is limited, MPs of inhalable size can reach respiratory tissues and cause damages [23,24]. Therefore, it is urgently necessary to quantitatively estimate inhalation exposure to MPs. Due to the analytical challenges of isolating and identifying MPs of inhalable size (i.e., aerodynamic diameter less than 10 μm), recent studies have been limited to relatively larger MPs in indoor and outdoor air [25-29]. In addition to the particle size, analyzing MPs in air samples is challenging because a larger sample volume is required for atmospheric MPs compared to those in other matrices, such as water, soil, and food. Moreover, isolating MPs from atmospheric particles is more susceptible to contamination.
Exposure to atmospheric particulate matter has long been a significant health issue [30-32]. It is well known that inhaled particles cause various diseases, and understanding their physical and chemical properties is crucial to elucidating the adverse outcome pathways of atmospheric particles [31-34]. Atmospheric particles may originate from several sources, including combustion, bioaerosols, minerals, and secondary formation [35,36]. Although the fraction of synthetic polymeric substances in atmospheric particulate matters might be low compared to particles of other origins, exposure to those emerging contaminants is considered an important environmental health issue [17,18,23-25].
In this study, the quantitative estimation of inhalation intake of MPs was conducted based on three plausible scenarios of particle size distribution: the Power law, unimodal log-normal, and bimodal log-normal distributions. Deposition of MPs in the size range of 0.1–10 μm in the human respiratory system was assessed using the multi-path particle dosimetry (MPPD) model [37], and parameter sensitivity was analyzed through Monte Carlo simulations.
Materials and Methods
Atmospheric particle size distribution of MPs
Although the presence of MPs in both outdoor and indoor air has been reported in many studies [25,26,28,29,38-40], most analyzed particles were larger than the inhalable size range (i.e., 0.1–10 μm in aerodynamic diameter). To the best of our knowledge, there are no reliable references available to estimate the size distribution of inhalable MPs. Thus, we assumed their size distribution to be similar to that of atmospheric aerosol particles. Despite the high spatiotemporal variability of atmospheric aerosols, the simplest way to represent particle size distribution is by assuming a Power law distribution [41] (Equation 1):
where N is the number concentration [m-3], dp is the characteristic particle diameter, and C and α are positive constants. For urban aerosols, their size distributions are often described as the sum of n log-normal distributions (Equation 2) [41].
Unlike particulate matter in the air, the particle size distribution of MPs in indoor and outdoor air has rarely been studied due to analytical challenges. Therefore, we developed three scenarios of MP distribution in air:
1. Power law distribution: Based on a typical exponent value of α = -3.75 for urban aerosols [41].
2. Unimodal log-normal distribution: Assuming coarse particles with
3. Bimodal log-normal distribution: Representing fine and coarse MP particles, with
Representative particle size distributions are shown in Figure 1.
Particle size distributions of MPs in air: distribution 1 assuming Power law distribution (α = −3.75); distribution 2 assuming unimodal log-normal distribution (
It is also well-known that spherical MPs are uncommon in environmental samples [25,28,43]. Although there is limited research on the shapes of MPs within the inhalable size range (0.1-10 μm), atmospheric MPs are likely to be predominantly microfibers or fragments. This assumption is based on the frequent observation of microfibers and fragments in atmospheric samples of larger particle sizes [25,28]. Typically, researchers classify particles as microfibers when the aspectIt is also well-known that spherical MPs are uncommon in environmental samples [25,28,43]. Although there is limited research on the shapes of MPs within the inhalable size range (0.1-10 μm), atmospheric MPs are likely to be predominantly microfibers or fragments. This assumption is based on the frequent observation of microfibers and fragments in atmospheric samples of larger particle sizes [25,28]. Typically, researchers classify particles as microfibers when the aspect ratio exceeds 3:1. In this study, the default shape of atmospheric MPs was assumed to be cylindrical, with a height-to-diameter ratio of 3:1. For this geometry, the characteristic diameter (dp) in Equations 1 and 2 relates to the cylinder diameter (dc) as follows [44]:
where V is the equivalent volume of a sphere. Since the mass median aerodynamic diameter (MMAD) was used for MPPD model simulations, the corresponding aerodynamic diameter (da) was estimated as 2.0 dc. This estimation accounts for the shape factor of a cylinder with an aspect ratio of 3 : 1, which is approximately 1.2 [44,45].
MPPD model
The multi-path particle dosimetry (MPPD) model (version 3.04) was employed to estimate the deposition of MP aerosols in human respiratory system. The Yeh/Schum 5-Lobe model, which incorporates a symmetric dichotomous branching pattern within lobes of differing structures, was used to simulate deposition across the entire lung.
Input parameters for the simulation are summarized in Table 1. The airway morphology was defined by functional residual capacity (FRC) and upper respiratory tract volume (URT). Particle properties were specified according to the distribution scenarios, including parameters such as diameter, density, shape, and physical distribution. Because the most abundant MP materials were polyethylene, polypropylene, polystyrene, and polyethylene terephthalate [4,29], the density of MP particles was assumed to be 1.0 g/cm3. Breathing parameters—breathing frequency, tidal volume, and inspiratory fraction—were set to 12 min−1, 625 mL, and 0.5, respectively, following default values suggested in the MPPD model [37]. Nasal breathing was assumed for the simulations.
Simulation parameters for the MPPD model.
Estimation of inhalation exposure to MPs
The mass of MPs in a specific size range (Mregion,i) deposited in three regions of the respiratory system – head (H), tracheobronchial (TB), and pulmonary (P) – was estimated under steady-state conditions using Equation 4.
where DFregion,i is the deposited fraction estimated by the MPPD model [-], Ca,i is the atmospheric concentration of MPs of a given size range in the air assumed in exposure scenarios [μg m-3], BR is the breathing rate [m3 min-1], and kclear,i is the clearance rate of MPs from the region [min-1].
The deposition fraction (DFregion,i) were obtained from the MPPD model, which provided total respiratory tract deposition as well as region-specific fractions for the head, tracheobronchial, and pulmonary regions. The default atmospheric MP concentration (Ca) was set at 0.1 μg m-3, and the BR was set at 0.0075 m3 min-1, values typical for an adult [37].
Both unimodal and multimodal particle size distributions were applied in the MPPD model simulations, enabling the estimation of region-specific deposition doses. It was assumed that inhaled MPs are predominantly larger than 1 μm. These larger particles are primarily deposited in the tracheobronchial region, where they are efficiently cleared by mucous and ciliary action [46]. The clearance process was incorporated using a fast human clearance rate (kclear,i) of 0.02 d-1 for the tracheobronchial region, consistent with MPPD model recommendations.
Sensitivity analysis
Since the three MP distributions described earlier do not fully capture the potential variability in inhalation intake at a given atmospheric concentration (Ca = 0.1 μg m–3), further sensitivity analyses were performed. The analyses evaluated the impact of particle size distribution parameters on inhalation exposure.
1. Power law distribution:
The exponent α was uniformly varied between 3 and 4 in the Monte Carlo simulations (n=10,000). For each simulation, the corresponding constant C was adjusted to maintain the toral atmospheric MP concentration. Since the deposition fraction from the MPPD model does not depend on aerosol particle concentration, a linear relationship was expected between total atmospheric MP concentration and deposited mass when the particle size distribution was unchanged.
2. Unimodal and bimodal distributions:
Input parameters for the MPPD model (n = 300) were randomly generated as outlined in Table 2. For the unimodal distribution, particle diameter and geometric standard deviation were varied uniformly within 3–7 μm and 1.2–1.7, respectively. For the bimodal distribution, the mass fractions of the smaller and the larger size modes were fixed at 0.1 and 0.9, respectively, to represent realistic atmospheric particle size distributions.
Input parameters for the MPPD model for Monte-Carlo simulation.
Results and Discussion
Estimation of lung deposition of MPs in human respiratory system
Table 3 summarizes the deposited mass of MPs in the three respiratory regions (head, tracheobronchial, and pulmonary) based on the default parameter values for each of the three particle size distribution scenarios. At a constant atmospheric concentration of MPs (0.1 μg m–3), the total mass of MPs deposited in the respiratory system was highest for the unimodal distribution (49.9 μg), followed by bimodal distribution (46.0 μg), and lowest for the Power law distribution (19.1 μg). The higher deposition in the unimodal distribution is attributed to the larger fraction of MPs in the micrometer size range compared to the other two distributions (Figure 1). MPs in this size range exhibit a higher deposition fraction in the respiratory tract, as estimated by the MPPD model, compared to smaller, sub-micrometer particles.
Estimation of mass deposition of microplastics using MPPD model for three particle size distributions.
Interestingly, the mass of MPs deposited in the pulmonary region was significantly higher (10.0 μg) when assuming the Power law distribution compared to the unimodal or bimodal log-normal distribution (6.1 or 5.9 μg, respectively), despite the total mass of MPs in the entire respiratory system being lowest for the Power law distribution. This discrepancy can be attributed to the fact that smaller particles, which tend to be more prevalent in the Power law distribution, are more likely to deposit in the pulmonary region. In general, smaller particles that deposit in the pulmonary region are cleared more slowly and pose a higher risk of adverse health effects. Particles deposited in the head and TB regions are likely to be removed via mucociliary clearance, whereas smaller particles deposited in the alveoli are likely to be internalized by alveolar macrophages and to enter the blood circulation [44,46,47]. Therefore, understanding both general and specific size distributions of atmospheric MPs is crucial for linking MP exposure to potential health impacts.
Model sensitivity analysis and comparison with human biomonitoring studies
The variation in the deposited mass across the three respiratory regions, assuming the parameter distributions outlined in Table 2, is depicted in Figure 2. The results were consistent with those obtained from the simulations using fixed parameter values (Table 3). Specifically, the total deposited mass followed the same order of magnitude: unimodal log-normal > bimodal log-normal > Power law distributions. The arithmetic mean and median values were found to be in close agreement with those presented in Table 3.
Variation in the deposited mass of MPs in three respiratory regions for (a) Power law (n=10,000), (b) unimodal log-normal (n=300), and (c) bimodal log-normal distributions (n=300) based on Monte Carlo simulations. The median is represented by the vertical line that divides the box into two parts. The upper and lower boxes are the upper and lower quartiles, respectively. The whiskers represent 1.5 times the interquartile ranges. Arithmetic mean values are also indicated inside the box.
In the MPPD model, the deposition fraction in different respiratory regions is estimated based on the aerodynamic properties of aerosols [37]. For cylindrical MPs with a density of 1.0 g cm–3, particles with an aerodynamic diameter greater than 5 μm are predominantly filtered in the head region (Figure 3). For example, the deposition fractions of cylindrical MPs with an aerodynamic diameter of 5 μm are 0.47, 0.06, and 0.19 in the head, tracheobronchial (TB), and pulmonary regions, respectively. In contrast, those for 0.2 μm MPs are 0.06, 0.08, and 0.19 in the head, TB, and pulmonary regions, respectively. Since the total deposition of MPs is dominated by deposition in the pulmonary region for MP particles smaller than 1 μm, it is crucial to understand the characteristic particle size distribution of MPs in the PM2.5 range, even though most recent studies have reported larger atmospheric MPs [25-29].
Deposition fraction in three respiratory regions estimated by the MPPD model with respect to the aerodynamic diameter of cylindrical MPs with an aspect ratio of 3:1 and particle density of 1.0 g cm–3.
Comparison with literature
To the best of our knowledge, no studies reported the occurrence of MPs in the 0.1–10 μm range in human respiratory tissues. Jenner et al. (2022) identified MPs larger than 10 μm using Fourier-transform infrared (FTIR) spectroscopy in human lung tissues [12]. Since they reported between “not detected” (n.d.) to 8 MP particles in 0.79-13.33 g of lung tissue, direct comparison with the steady-state mass of MPs (0.1–10 μm) deposited in the respiratory system in this study is not possible. However, the accumulated mass of larger MPs could be estimated based on the length of fiber or fragment- type MPs reported in their study, assuming an aspect ratio of 3:1. The estimated mass concentration of large MPs ranges from n.d. to 202 μg g–1, corresponding to 18 56 μg g–1. Considering the typical size of lungs (~ 1 kg), the steady-state deposited mass of MPs in human lungs could be in the milligrams range (a few to several hundred mg), which is much greater than the few tens of micrograms estimated in this study assuming an atmospheric MP concentration of 0.1 μg m–3. Since the deposited mass of MPs estimated using the MPPD model is linearly related to the atmospheric concentration, Ca should be at least two to three orders of magnitude higher to yield comparable masses of MPs in the 0.1–10 μm range to those of large MPs identified by Jenner et al. (2022) [12], resulting in an unrealistically high Ca for MPs. Therefore, the mass of MPs in 0.1–10 μm range in human respiratory systems should be much lower than that of MPs > 10 μm, which can be identified using FTIR, although those smaller MPs are of a more serious health concern. Similarly, the interquartile range of MPs identified in human sputum samples using FTIR was 44.67–210.64 μm [48], making it difficult to assess exposure to MPs within 0.1–10 μm range. Therefore, it is urgently needed to determine the levels of MPs in human respiratory systems within the PM10 and PM2.5 ranges.
Conclusions
This study provides a quantitative estimation of the inhalation intake of MPs using the MPPD model under various scenarios of particle size distribution. Our findings highlight that while the total mass of MPs deposited in the human respiratory system depends significantly on the assumed size distribution, smaller MPs (< 1 μm) are more likely to reach the pulmonary region, where clearance is slower and potential health risks are greater. Sensitivity analyses confirmed the robustness of the deposition patterns, emphasizing the importance of understanding the characteristic size distribution of MPs in atmospheric particulate matter, particularly in the PM2.5 range. Comparison with biomonitoring studies suggests that the steady-state deposited mass of MPs in the 0.1–10 μm range is likely much lower than that of larger MPs (>10 μm), which are more readily detected in human lung tissues and sputum samples. Nonetheless, smaller MPs may pose more severe health risks due to their deeper deposition and prolonged retention in the respiratory tract. These results underscore the critical need for further research to characterize the occurrence, size distribution, and health impacts of MPs within the inhalable range in both environmental air and human tissues. Precise monitoring of MPs in the PM10 and PM2.5 range will be essential to better understand and mitigate potential adverse health outcomes associated with MP inhalation.
Notes
Acknowledgement
This work was supported by the Korea Environment Industry & Technology Institute (KEITI) through the Technology Development Project for Safety Management of Household Chemical Products Program funded by the Korea Ministry of Environment (MOE) (202300230430).
Conflict of interest
None.
CRediT author statement
YC: Data Curation, Methodology, Software, Writing – Original draft; IC: Data curation, Methodology; JHK: Conceptualization, Investigation; Supervision, Writing – Original draft; Writing – Reviewing and Editing.