Estimation of the Seasonal Inhaled Deposited Dose of Particulate Matter in the Respiratory System of Urban Individuals Living in an Eastern Mediterranean City

In this study, we present an estimation for the inhaled deposited dose rate in adult males and females during common exposure scenarios to urban background aerosols in an Eastern Mediterranean city (Amman, Jordan) based on a one-year database of measured particle number size distribution. The dose rates show seasonal variations reflecting the physical characteristics (i.e., modal structure) of the particle number size distribution. An additional factor was the varying deposition fraction (DF) for different regions and different human activities (exercising versus resting). The total dose rate was 3 × 109–65 × 109 particles/h (PM2.5 and PM10 doses 1–22 µg/h and 9–210 µg/h; respectively) depending on the gender, activity, and season. Based on the particle number metrics, the inhaled deposited dose in the head, Tracheobronchial, and alveolar were 7–16%, 16–28%, and 56–76%; respectively. Based on the PM2.5 metric, the corresponding dose rate was 9–41%,13–19%; and 46–72% respectively. As for the PM10 metric, they were 25–75%, 7–35%, and 15–55%; respectively.


Introduction
Urban aerosols have gained increased attention over the past decades because they have clear health effects related to their exposure [1,2]. Health studies and air quality regulations have been based on the mass concentration of particulate matter (PM); however, recent studies have increased the awareness about the importance of the number concentration as a complementary metric needed to understand the health effects and exposure. This has been evident from the fact that submicron particles penetrate deep into the respiratory system reaching the alveolar region, where the blood can carry particulate matter and circulate them in different organs causing serious health effects in the human body [3]. Besides their health effects, ultrafine particles (UFP, diameter < 0.1 µm) can act as cloud condensation nuclei (CCN) affecting the climate [4,5].
Ultrafine particles (UFP, diameter < 0.1 µm) do not have a significant fraction in the total mass concentration but they have a significant fraction in the number concentration in urban areas. Besides that, UFP emanate from a complex variety of sources (primary and secondary) that are directly linked to anthropogenic activities. Primary particles are directly emitted into the atmosphere. Secondary particles are produced in the atmosphere via gas-toparticle transformation, which has been known as new particle formation (NPF) observed in various environments and contributing to a major fraction of the total particle number budget [6][7][8]. The complexity of urban aerosols comes from the fact that different sources may entangle them in the same particle size range that becomes difficult to distinguish 1.
Calculated the 5-min average of the SMPS data; 2.
Omitted the first channel in the OPS (i.e., the remaining diameter range was 0.32-10 µm); 4.
Merged the two distributions.

Regional Inhaled Deposited Dose
According to the ICRP and MPPD models [21,22], the respiratory tract is divided into three regions: head/throat, tracheobronchial (TB), and pulmonary/alveolar (P/Alv). Following our previous methodology [18,19,23], the regional inhaled deposited dose can be calculated for a specific particle diameter range (D p1 -D p2 ) during a one-hour exposure period, which is known as the dose rate: where V E is the minute ventilation (volume of air breathed as reported by Holmes [24], Table S1), DF(D p ) is the aerosol deposition fraction in a particular region of the respiratory tract ( Figure S1, Löndahl et al. [25]), n N 0 (D p ) (particles/cm 3 ) is the particle number size distribution (i.e., dN/dlog(D p )), and f is a metric conversion for the aerosol concentration (i.e., it is 1 for particle number and for particle mass = ρ p D p 3 π/6, where ρ p is the particle effective density). Note that the inhaled deposition fraction (DF(D p )) and the particle number size distribution (n 0 N (D P )) are functions of particle diameter (D p ). The details about the calculation of the regional inhaled deposited dose rate are described in the Supplementary Material (Section S4). The results herein are presented based on the mean particle number size distribution. As a measure of the uncertainty of the calculation, we shall discuss the results with respect to the quartiles of the aerosol concentrations.

Exposure Scenarios
The regional inhaled deposited dose rates were calculated for adult male and female occupants during different activity levels: 1.
Resting, such as sitting and standing.

2.
Exercising, such as walking, running, and yard working.
The combination of subjects (male/female), activities (resting/exercising), and exposure levels (different time of the year, month, week, and day) reflect common exposure scenarios in the urban background atmosphere of Amman, which can be a good example for an Eastern Mediterranean city. The required respiratory tract parameters (i.e., V E and DF) are described in detail in Figure S3 and Table S1. As for the exposure parameters, these are taken from the aerosol database for the particle number size distribution (n N 0 (D p )).
The coarse mode particle number (PN Coarse ) concentration had a different seasonal pattern than that of PN Sub . PN Coarse was the highest during the autumn and spring. This seasonal pattern is closely linked to the sand and dust storms (SDS) in the spring season and local dust resuspension in the autumn. The daily average PN Coarse often exceeded 2 cm −3 (as high as 14.5 cm −3 ) during SDSs and the hourly average reached values as high as 46 cm −3 .
As shown in Figure S9, the particle number size distribution also showed clear variation in its modal structure with respect to the time of the year, as well as the time of the day. For example, the UFP modes had higher concentrations during the winter (December-February) than in the summer (June-August). During the traffic rush hours (morning and afternoon) the UFP particle modes also had higher concentrations than during the early morning (before 6:00).
Interestingly, the seasonal dose rate showed a different cycle when considering the PM 2.5 metric (Figure 1c,d). In this case, the dose rate was the highest during the autumn (specifically around October and November) and the spring (specifically around March and April). Similar to the particle number metric, the lowest dose rate was also seen in the summer. Quantitively, the monthly total dose rate in the summer (June-August) was around 7, 3.5, 2.7, 1.7, and 1.4 µg/h for an adult male, and for the same order of the abovementioned activities. During the winter (December-February), the corresponding dose rate was about 15, 7.6, 6, 4, and 3.3 µg/h. During the spring (March-May), the dose rate was as high as 20, 10, 7.5, 5.4, and 4.4 µg/h and during the autumn (September-November), it was as high as 22, 11, 8.5, 6, and 4.8 µg/h. The corresponding dose rates for an adult female were lower than those for an adult male; the ratios between the genders varied between 66% and 88% depending on the activity and the season. The reason for these differences between females and males can be explained by the differences in the body size (i.e., lungs size) and breathing minute ventilation (i.e., V E ). The female lungs' size is smaller than those of a male, and consequently, their V E is lower.
With respect to the PM 10 metric, the differences in the dose rate were marginal between the summer and winter and the highest dose rates were observed during the autumn followed by the spring (Figure 1e,f). Similar to the PM 2.5 metric, the corresponding dose rate for an adult female was lower than those for an adult male with the ratio between 61% and 91% depending on the activity and the season. Quantitively, the monthly total dose rate in the summer was around 55, 28, 22, 12, and 9 µg/h for an adult male, and for the same order of the above-mentioned activities. During the winter, the corresponding dose rate was about 81, 40, 32, 17, and 14 µg/h. During the spring, the dose rate was as high as 171, 85, 67, 36, and 29 µg/h and during the autumn was as high as 210, 105, 82, 43, and 35 µg/h.
Based on the seasonal variation of the dose rate with respect to the two metrics (i.e., particle number versus particle mass), it is obvious that there is a contradicting result regarding when to avoid high dose rates received in the respiratory system. For example, according to the particle number dose rates, the highest probability of receiving high dose rates is expected in the winter, namely during December and January. However, when considering the particle mass, the highest dose rate is expected to be received during the autumn (namely October and November) and the spring (namely March and April). The important question comes here: which metric shall we consider? In order to answer that, more investigations shall be made to study the health effects with the respect to different aerosols metrics in addition to the composition and toxicity. For instance, the lung deposition surface area (LDSA) is one of the metrics, but this alone will have a limitation to making constructive conclusions.
for the same order of the above-mentioned activities. During the winter, the corresponding dose rate was about 81, 40, 32, 17, and 14 µg/h. During the spring, the dose rate was as high as 171, 85, 67, 36, and 29 µg/h and during the autumn was as high as 210, 105, 82, 43, and 35 µg/h. Based on the seasonal variation of the dose rate with respect to the two metrics (i.e., particle number versus particle mass), it is obvious that there is a contradicting result regarding when to avoid high dose rates received in the respiratory system. For example, according to the particle number dose rates, the highest probability of receiving high dose rates is expected in the winter, namely during December and January. However, when considering the particle mass, the highest dose rate is expected to be received during the autumn (namely October and November) and the spring (namely March and April). The important question comes here: which metric shall we consider? In order to answer that, more investigations shall be made to study the health effects with the respect to different aerosols metrics in addition to the composition and toxicity. For instance, the lung deposition surface area (LDSA) is one of the metrics, but this alone will have a limitation to making constructive conclusions.  The variation in the dose rates based on the metric calls for an urgent deep investigation to better understand the health effects not only based on the PM 2.5 but also on the PN Sub . This fact is further revealed when looking at the regression plots of each dose rate metric with respect to the modal structure of the particle number size distribution (i.e., simplified as the concentration of each individual mode: nucleation (D p 10-25 nm), Aitken (D p 25-100 nm), accumulation (D p 0.1-1 µm), and coarse (D p 1-10 µm)) shown in Figures 2-4. Quantitively, this is reflected by the R 2 and the correlation coefficient (r) ( Tables 1-3). The PN Sub inhaled deposited dose metric had the highest R 2 and r with the total particle number concentration and the ultrafine particles (diameter < 100 nm). The other two metrics based on the particle mass (i.e., PM 2.5 and PM 10 ) had the highest R 2 and r with coarse particle size fraction.
The variation in the dose rates based on the metric calls for an urgent deep investigation to better understand the health effects not only based on the PM2.5 but also on the PNSub. This fact is further revealed when looking at the regression plots of each dose rate metric with respect to the modal structure of the particle number size distribution (i.e., simplified as the concentration of each individual mode: nucleation (Dp 10-25 nm), Aitken (Dp 25-100 nm), accumulation (Dp 0.1-1 µm), and coarse (Dp 1-10 µm)) shown in Figure 2, Figure  3 and Figure 4. Quantitively, this is reflected by the R 2 and the correlation coefficient (r) ( Table 1, Table 2 and Table 3). The PNSub inhaled deposited dose metric had the highest R 2 and r with the total particle number concentration and the ultrafine particles (diameter < 100 nm). The other two metrics based on the particle mass (i.e., PM2.5 and PM10) had the highest R 2 and r with coarse particle size fraction.

Figure 2.
Regression scatter plots between the inhaled deposited dose rate (based on the particle number PNSub metric) and the particle number concentration of (a,b) nucleation mode, (c,d) Aitken mode, and (e,f) accumulation mode. The left panel is the inhaled dose rate calculated for an adult male and the right panel for an adult female. Regression scatter plots between the inhaled deposited dose rate (based on the particle number PN Sub metric) and the particle number concentration of (a,b) nucleation mode, (c,d) Aitken mode, and (e,f) accumulation mode. The left panel is the inhaled dose rate calculated for an adult male and the right panel for an adult female.

Regional Inhaled Deposited Dose Rate
The regional inhaled deposited dose (Illustrated as the percentage fraction Figures 5  and 6) also showed a clear seasonal variation. Based on the particle number metric, the exercising dose rate (Figure 5a) in the head was rather identical for both males and females and had its minimum value (about 7%) during the winter and its maximum during the summer (about 7.5%). The exercising dose rate in the Tracheobronchial (Figure 5c) also showed a similar seasonal variation but the females had a high fraction (18-20%) than that of the males (16-18%). As for the exercising dose rate received in the Alveolar (Figure 5e), it showed an opposite seasonal variation to those of other regions (i.e., maximum in the winter) and was higher for males (74-76%) than females (73-75%). During resting (Figure 5b,d,f), the differences in the regional dose rates between males and females were more pronounced but followed similar seasonal variations as those for during exercising: around 14%, 23%, 63%, respectively, in the head, Tracheobronchial, and Alveolar, for an adult male versus 16%, 28%, and 56% for an adult female.   3.2.2. Regional Inhaled Deposited Dose Rate The regional inhaled deposited dose (Illustrated as the percentage fraction Figure 5 and Figure 6) also showed a clear seasonal variation. Based on the particle number metric, the exercising dose rate (Figure 5a) in the head was rather identical for both males and female and had its minimum value (about 7%) during the winter and its maximum during the sum mer (about 7.5%). The exercising dose rate in the Tracheobronchial (Figure 5c) also showed a similar seasonal variation but the females had a high fraction (18%-20%) than that of the male (16%-18%). As for the exercising dose rate received in the Alveolar (Figure 5e), it showed an opposite seasonal variation to those of other regions (i.e., maximum in the winter) and was higher for males (74%-76%) than females (73%-75%). During resting (Figure 5b,d,f) Based on the PM metrics, the regional inhaled deposited dose rates were rather similar for males and females. However, the seasonal trend was less pronounced for the PM 2.5 metric ( Figure 6): it was around 9%, 19%; and 72%, respectively, in the head, Tracheobronchial, and Alveolar during exercising versus 41%, 13%, and 46% during resting. As for the PM 10 metric, the exercising and resting head dose rates were minimum during the winter and varied within 25-45% and 45-75% (Figure 7a,b). In contrast, the exercising and resting Alveolar dose rates were maximum during the winter and varied within 25-55% and 15-45% (Figure 7e,f). The Tracheobronchial dose rate seasonal variation varied between 25-35% and similar to that of the Head during exercising (Figure 7c) and 7-18% and similar to the Alveolar during resting (Figure 7d). Table 1. Coefficient of determination (R 2 ) and correlation coefficient (r) calculated for the regional inhaled deposited dose (PN Sub ) with respect to the size/fractionated particle number concentrations: nucleation mode (NUCL, 10-25 nm), Aitken mode (AITK, 25-100 nm), accumulation mode (ACCU, 0.1-1 µm), coarse mode (COAR, 1-10s µm), and the total diameter range (Total, 10 nm-10 µm).  Table 2. Coefficient of determination (R 2 ) and correlation coefficient (r) calculated for the regional inhaled deposited dose (PM 2.5 ) with respect to the size/fractionated particle number concentrations: nucleation mode (NUCL, 10-25 nm), Aitken mode (AITK, 25-100 nm), accumulation mode (ACCU, 0.1-1 µm), coarse mode (COAR, 1-10s µm), and the total diameter range (Total, 10 nm-10 µm).   Table 3. Coefficient of determination (R 2 ) and correlation coefficient (r) calculated for the regional inhaled deposited dose (PM 10 ) with respect to the size/fractionated particle number concentrations: nucleation mode (NUCL, 10-25 nm), Aitken mode (AITK, 25-100 nm), accumulation mode (ACCU, 0.1-1 µm), coarse mode (COAR, 1-10s µm), and the total diameter range (Total, 10 nm-10 µm).  Surprisingly and contrary to what we expected, the regional dose rate seasonal variation for the PM 10 (illustrated as the percentage fraction) was not similar to that of the coarse mode concentrations ( Figure S8). Surprisingly, the PM 2.5 was the one that showed rather similar seasonal variation to that of the coarse mode concentrations.
In fact, the varying physical characteristics (i.e., modal structure) of the particle number size distribution ( Figure S9) through the year (i.e., seasonal variation) was the critical factor in defining the regional inhaled deposited dose rate. This is in addition to the varying deposition fraction (DF) for different regions and different human activities (exercising versus resting) ( Figure S3).
Recalling the particle number concentrations are dominated by the UFP fraction as discussed in Section 2.1 "Summary about the particulate matter concentrations", then it can be used to check the accuracy of the calculated dose rate based on the particle number concentrations. For instance, the difference between the monthly mean and the corresponding 25% of the UFP concentrations (and the submicron particle concentrations) was about 40%. Similarly, the difference between the monthly mean and the corresponding 75% of the UFP concentrations was about 30%. This means that the monthly dose rate varies between 30% and 40% based on the particle number concentrations. As for the dose rate calculated in terms of particle mass metrics, the monthly dose rate is expected to vary between 15% and 50%, which reflects the mass concentration variability of the accumulation and coarse modes. Based on the PM metrics, the regional inhaled deposited dose rates were rather sim ilar for males and females. However, the seasonal trend was less pronounced for the PM2 metric ( Figure 6): it was around 9%, 19%; and 72%, respectively, in the head, Tracheobron chial, and Alveolar during exercising versus 41%, 13%, and 46% during resting. As for th PM10 metric, the exercising and resting head dose rates were minimum during the winte and varied within 25%-45% and 45%-75% (Figure 7a,b). In contrast, the exercising and resting Alveolar dose rates were maximum during the winter and varied within 25%-55% and 15%-45% (Figure 7e,f). The Tracheobronchial dose rate seasonal variation varied be tween 25%-35% and similar to that of the Head during exercising (Figure 7c) and 7%-18% and similar to the Alveolar during resting (Figure 7d). The limitation of this study relies on several factors: (1) the measured particle number concentrations were selected for urban background conditions, (2) the calculations were made by assuming the exposure time as outdoors only, (3) the calculations were made based on seasonal variation, (4) the selected scenarios were limited to adult male/female and four activities, and (5) the conversion from particle number to particle mass concentration has some limitations (such as lack of information about particle density, shape, and chemical composition). The first and second limitations imply that the calculated dose rates here in this study represent a lower estimation for the real dose because urban people are exposed to a variety of environments, which vary from background to polluted areas (i.e., traffic, industry, etc.). Usually, people spend most of their time indoors being exposed to different types and levels of pollutants. The third limitation can be taken care of by recalculating the dose rates by using higher time resolutions (e.g., daily or hourly). The selected scenarios (fourth limitation) can be extended to more realistic human activities such as the typical daily behavior of an urban person. The fifth limitation cannot be taken care of unless detailed aerosol sampling is made aiming at gaining better knowledge about the physical-chemical properties of aerosols. The chemical composition might affect the hygroscopicity of particulate matter; which, in turn, affects the deposition pattern in the respiratory system.   Surprisingly and contrary to what we expected, the regional dose rate seasonal vari ation for the PM10 (illustrated as the percentage fraction) was not similar to that of the coarse mode concentrations ( Figure S8). Surprisingly, the PM2.5 was the one that showed rather similar seasonal variation to that of the coarse mode concentrations.
In fact, the varying physical characteristics (i.e., modal structure) of the particle num ber size distribution ( Figure S9) through the year (i.e., seasonal variation) was the critica factor in defining the regional inhaled deposited dose rate. This is in addition to the var ying deposition fraction (DF) for different regions and different human activities (exercis ing versus resting) ( Figure S3).
Recalling the particle number concentrations are dominated by the UFP fraction as discussed in Section 2.1 "Summary about the particulate matter concentrations", then i

Conclusions
In this study, we presented an estimation for the inhaled deposited dose rate in adult males and females during common exposure scenarios (i.e., human activities of exercising and resting) to urban background aerosols in an Eastern Mediterranean city. The calculations were based on a one-year database of the measured particle number size distribution in Amman, Jordan. The analysis of the inhaled deposited dose rate included seasonal variation and regional doses in the respiratory system.
A quick glance at the aerosol database indicates that the ultrafine particle number concentration (PN UFP , diameter < 0.1 µm) constitutes about 93% submicron aerosols. Aerosols of different particle size fractions showed clear temporal variations: seasonal, weekly, and diurnal reflecting the temporal variation of the anthropogenic activities and influencing factors such as meteorological conditions. The daily mean of the submicron particle number concentration (PN Sub ) was within the range of 1.2.3 × 10 4 -3.7 × 10 4 cm −3 with high concentrations during the winter. The coarse mode particle number (PN Coarse ) concentration had a different seasonal pattern with high concentrations during the autumn and spring reflecting sand and dust storms (SDS) in the spring season and local dust resuspension in the autumn. The daily average PN Coarse often exceeded 2 cm −3 (as high as 14.5 cm −3 ) during SDS episodes.
In general, the varying physical characteristics (i.e., modal structure) of the particle number size distribution through the year (i.e., seasonal variation) was the critical factor in defining the regional inhaled deposited dose rate in addition to the varying deposition fraction (DF) for different regions and different human activities (exercising versus resting).

Supplementary Materials:
The following are available online at https://www.mdpi.com/article/ 10.3390/ijerph19074303/s1, S1: geographical location, Figure S1 Figure S2: Experimental penetration efficiency through the sampling lines (tubing and diffusion drier); S3. Data handling; S4. Regional Inhaled Deposited Dose Rate, Figure S3. Size-resolved deposition fraction (DF) curves for the respiratory tract of adult subjects: (a) male exercising, (b) male at rest, (c) female exercising, and (d) female at rest. Data were adopted from Löndahl et al. [25] and the ICRP and MPPD models [15,21], Table S1. Minute ventilation (volume of air breathed), V E (m 3 /h), for adult subjects according to Holmes (1994). The last column indicates the deposition fraction curve used for the listed activity ( Figure S3); S5. Summary of the aerosol database and particulate matter concentrations, Figure S4. Time series of the (a) submicron particle number concentration, (b) comparison between the condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) + optical particle sizer (OPS) particle number concentrations, and (c,d) the main particle size fraction concentrations of ultrafine particles (Dp < 0.1 µm) and accumulation mode particles (Dp 0.1-1 µm), Figure S5. (a) Diurnal pattern of the submicron particle number concentration (0.01-1 µm) and (b) date-time spectrum showing the day-to-day and hour-to-hour variation of the number concentration; the color bar scales the number concentration (cm −3 ), Figure S6. Diurnal pattern of the (a) ultrafine particle number concentration (UFP, diameter < 0.1 µm) and (b) accumulation mode particle number concentration (diameter 0.1-1 µm), Figure S7. Date-time spectra showing the day-to-day and hourto-hour variation of (a) ultrafine particle number concentration (UFP, diameter < 0.1 µm) and (b) accumulation mode particle number concentration (diameter 0.1-1 µm). The color bar scales the number concentration (cm −3 ), Figure S8. (a) Time series of the coarse mode (diameter 1-10 µm) particle number concentration and (b) date-time spectrum showing the day-to-day and hour-to-hour variation of the number concentration; the color bar scales the number concentration (cm −3 ), Figure  S9. Mean particle number size distributions during (a,b) cold period (i.e., December-February) and (c,d) warm period (i.e., May-August). The mean distributions are shown for different times of the day on workdays (left panel) and weekend days (right panel), Table S2: Monthly statistics for the main particle size fractions (concentrations in units of cm −3 ).