(288d) PAH Exposure and LUNG Cancer Risk Assessment By Internal Dosimetry Metrics

This study deals with the assessment of cancer risk attributable to PAH exposure, largely connected to the increased use of biomass for space heating in Greece in the winter of 2012-2013. Towards this aim, several methodological elements have to be integrated Towards this aim, several methodological elements have to be integrated, including:

-          PM measurements for the three main fractions (PM10. PM2.5 and PM1). This is essential, since smaller PM fractions have been associated to biomass burning . Measurements include two different sampling sites (one representative of the urban background levels and one for traffic), in order to differentiate the amount and the composition of PM attributed to contribution of different sources.

-          PM chemical analysis, aiming at:

• identifying their carcinogenic potency, through PAHs composition analysis.
• identifying their origin, through levoglucosan and black carbon (BC) analysis. Levoglucosan is considered as the most specific biomass burning tracer, while BC is considered as product of internal combustion sources.

-          Refining the exposure and associated risk assessment methodology. Exposed population was divided to eight age-groups, ranging from infants to adults (>21 years old). Different types of daily activities demand different levels of effort that correspond to different inhalation rates. For the estimation of human exposure to PAHs, weighted average daily inhalation rate (IR_i, m³/day) was calculated for each age group. Calculations refer to the time-activity pattern of individuals for a period of one week. It is known that PM of different size interact differently with the Human Respiratory Tract (HRT). PM from biomass burning has specific characteristics, which have to be taken into account when estimating the associated risk. HRT particle deposition modeling was applied for the determination of PM deposition fraction (DF) to the three parts of the pulmonary system in order to estimate the internal dose of PAHs. Main mechanisms of PM deposition across HRT include diffusion, sedimentation and impaction. Secondary mechanisms involve interception and electrostatic deposition. Different HRT regions involve different deposition mechanisms, with regard to different PM size as follows: 1. Naso-pharyngeal region (or upper respiratory tract – URT): impaction, sedimentation, electrostatic deposition. 2. Tracheo-bronchial (TB) region: impaction, sedimentation, diffusion. 3. Pulmonary/alveolar (P) region: sedimentation, diffusion.  PM deposition is affected by the particle properties (concentration and size distribution), air flow parameters (lung capacity and breathing frequency) and HRT physiology (structure and morphology). HRT deposition was calculated using the multiple path particle deposition (MPPD) v.2.1 model. Calculation of the overall toxicity of the mixture of PAHs is done using toxic equivalency factors (TEFs). The lung cancer risk attributed to PAHs depends on the amount of TEQ deposited across the middle (TB) and lower (P) HRT regions, calculated as the sum of the products of the different size fractioned PM mass deposited across the different HRT regions, multiplied by the Toxic Equivalent Concentration (TEQ) estimated for the specific size fraction. Genotoxic effects of PAHs were estimated by calculating the amount of TEQ deposited across the middle (TB) and lower (P) HRT regions to a slope factor of 3.8×10^-6 (kg×day)/ng B[a]P, calculated from the respective Inhalation Unit Risk for B[a]P (IUR_B[a]P), of 1.1×10^-3 m³/μg.

The latter allows us to estimate for a PM fraction of given size the actual amount of PAHs coming in contact with the lower respiratory tract. Using this refined exposure assessment approach, differences in physiology among different age groups/susceptible populations are taken into account in the corresponding cancer risk estimates.

Results showed that PM concentrations were higher in Greece during the cold months of the year, mainly due to biomass use for space heating. PAH and levoglucosan levels were highly correlated, indicating that governed the genotoxic effect of exposure to PMs.

Different size-distributed particle fractions are deposited across the different HRT regions, as a result of the different deposition processes occurring in the different regions of the HRT, which are related to the physiology/morphology of the respiratory system and the PM size distribution. This has been verified by a variety of lung deposition computational and experimental efforts. HRT deposition results indicate that the lower respiratory tract of infants and children (up to 14 years old) can retain up to 74% higher mass fraction of PM_1.0 particles than that of adults. The maximum difference in the thoracic deposition between adults  and children between 3 and 8 years old reaches 68 and 230% for the PM_2.5 and PM₁₀ fractions respectively. Thus, the PM_2.5 and PM_1.0 fractions rather than PM₁₀contribute to a greater extent to the absorption of PAHs by the respiratory tract in younger individuals than in adults. Although particle deposition in infants and children has been poorly studied and a high variability between individuals has been observed, key factors that influence the thoracic deposition of particles in children are lower ventilation rates (l/min), which favor deposition by sedimentation, a process that governs the deposition of larger inhalable particle diameters resulting in increased overall particle deposition profiles, as well as lower functional residual capacity FRC volumes.

Individuals who reside near the urban background site experience a higher risk (above 10^-6). Individual lifetime risk is higher for children, due to the higher bodyweight normalised dose of PMs and the amount of PAHs deposited at lower HRT regions. A higher fraction of smaller particles is deposited across the children respiratory tract, resulting in higher PAH burden.

The estimated lung cancer risk was non-negligible for residents close to the urban background monitoring site. Higher risk was estimated for infants and children, due to the higher bodyweight normalized dose and the human respiratory tract (HRT) physiology. HRT structure and physiology in youngsters favor deposition of particles that are smaller and more toxic per unit mass. In all cases, the estimated risk (2.8×10^-6 and 7.6×10^-7 for younger infants and adults at the urban background site and   9.5×10^-7 to 2.3×10^-7 for the traffic site, respectively was lower to the one estimated by the conventional methodology (4.7×10^-6 and 1.6×10^-6for the urban background and the traffic site respectively) that is based on Inhalation Unit Risk; the latter assumes that all PAHs adsorbed to particles are taken up by humans.

This study provides new information on the toxicity of PM emitted from biomass burning based on a refined exposure and risk assessment methodological framework which takes into account the mechanisms of internal exposure to particulate matter. On this basis we could estimate health risk taking into account not only the spatial distribution of airborne particles, but also variance observed among different age groups. Our results suggest that the integrated mechanistic approach developed herein describes in more detail the interaction between toxicants adsorbed onto airborne particles and health effects on the urban population. This is clearly illustrated by comparing the relative risk between the people living in the two different sampling sites of our study. The non-mechanistic methodology that takes into account only TEQ and IURreflects only differences in ambient air PAHs/TEQ levels. The mechanistic methodology proposed herein, incorporates the effect of complex environmental, physicochemical and physiological processes. These include:

(a)    the PM size distribution emitted from biomass burning;

(b)   the PAH adsorption on the different particle size fractions;

(c)    the deposition distribution of different PM size fractions across the human respiratory tract.

The PM size distribution affects the way these are distributed across the different HRT regions. In turn, the deposition profile of PM across the HRT varies with age of the exposed individuals due to age- dependent differences in respiratory physiology. Thus, risk assessment can take into account that a higher fraction of small diameter particles (also found to be more toxic per unit of particles mass) are deposited in the middle and lower HRT. By incorporating all these parameters, the risks associated to the increased PM and PAHs due to biomass burning are further differentiated by source and age of the exposed population. Using the IUR methodology, cancer risk estimates for the population living close to the two sampling sites differ by a factor of three. This reflects only the difference of PAH levels found on PM10. With the methodology proposed in this work, the estimated cancer risk at the two sites differs by a factor of five to seven depending on the age group. Thus, the IUR method would result in significant underestimation of the actual cancer risk related to the particulate matter from biomass burning.