2008 Progress Report: Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
EPA Grant Number:
Subproject: this is subproject number 003 , established and managed by the Center Director under
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Wexler, Anthony S.
Project 3 --
Inhalation Exposure Assessment of San Joaquin Valley Aerosol
Pinkerton, Kent E.
, Bonham, Ann
, Kleeman, Michael J.
Pinkerton, Kent E.
Kleeman, Michael J.
University of California - Davis
EPA Project Officer:
October 1, 2005 through
September 30, 2010
(Extended to September 30, 2011)
Project Period Covered by this Report:
October 1, 2007 through September 30,2008
Particulate Matter Research Centers (2004)
Epidemiological evidence suggests that the association between cardiac mortality and PM 10 concentrations changes between the summer and winter months in the San Joaquin Valley (SJV). This shift is likely caused by seasonal variation in the size and composition distribution of airborne particles. This project will perform inhalation exposure and particle characterization studies at rural and urban locations in different seasons to quantify the features of the airborne particles that are associated with adverse health effects.
Inhalation exposure studies will be carried out using mice that are exposed to ambient airborne particles and concentrated ambient airborne particles in the San Joaquin Valley. Exposures will be conducted in the summer and winter in both an urban and rural location to take advantage of the changes that occur in particle chemical composition and size distribution as a function of season and location. Heart rate variability, lung inflammation, and markers for oxidative stress will be monitored. Collocated measurements of PM2.5 and PM0.1 composition will be made to quantify health effects associated with chemical composition and support source apportionment calculations. Inhalation studies of direct emissions will be conducted for the dominant sources of PM2.5 and PM0.1 that are identified during ambient studies. Based on our results, we will postulate possible mechanisms for health effects and test these using laboratory studies and simple model particles.
Progress by Specific Aim
1. Differences in particle concentration, size distribution, and composition that occur as a function of season and location in the San Joaquin Valley (SJV) result in different health outcomes; these outcomes can be detected during inhalation exposure experiments.
We have now completed four field measurement and exposure studies in the San Joaquin Valley. These include an urban site located in Fresno, CA (500 East Shaw Avenue) for the summer and winter seasons, as well as a rural site located at Westside, CA also studied during the summer and winter seasons. The field studies in Fresno were conducted September 5-16, 2006, and February 13-24, 2007. The field studies in Westside were conducted August 14-25, 2007 and February 6-17, 2008. In each study male C57/BL6 mice were exposed to concentrated ambient particles (CAPs) for 6 hours/day, 5 days/week for two weeks. Fine/ultrafine ambient particles were collected and concentrated onsite using a Versatile Aerosol Concentrator Enhancement System (VACES). CAPs samples collected during each exposure were analyzed for chemical composition. The results of these exposure studies are ongoing, but are reported in part in this progress report.
2. The increased toxicity of airborne particles during the winter season in the SJV is associated with increased concentrations of ultrafine carbon particles.
A multi-pronged approach is being applied to examine the cardiopulmonary consequences of particle exposure, i.e., using both whole body to 1) evaluate cellular and inflammatory indicators in the lungs by bronchopulmonary lavage and cytokine measurements, 2) measure vascular components in platelets and other blood elements, 3) examine heart tissues directly for histopathology and 4) measure neurological changes in gene expression for pro-inflammatory cytokines.
3. The increased toxicity of airborne particles in the SJV during the winter season is associated with increased concentrations of accumulation mode ammonium/nitrate/sulfate particles.
Ambient and CAPs concentrations for the summer (2006) and winter (2007) Fresno and the summer (2007) and winter (2008) Westside Concentrated Ambient Particles (CAPs) exposures have been determined. These values are shown in the table below. RAAS represents the average ambient concentration of particles, while CAPs represents the enhanced concentration of particles to which the mice were exposed. The enhancement factor of ambient particles using the Virtual Aerosol Concentrator Exposure System (VACES) is also shown in the table below.
The chemical speciation for the Fresno and Westside summer and winter studies is also complete for nitrates, sulfates, bromine, ammonium, sodium, chloride, elemental carbon and organic carbon. The measurement for a number of trace elements has also been completed. These elements include potassium, vanadium, iron, lead, arsenic, calcium and barium.
4. The health effects of San Joaquin Valley aerosol can be directly related to the emissions source of the fine and ultrafine particles.
We have completed the lung cytokine analysis of the summer (2006) and winter (2007) Fresno and the summer (2007) and winter (2008) Westside Concentrated Ambient Particles (CAPs) exposures. Bronchoalveolar lavage analysis for these same locations and seasons demonstrated no significant changes in total cells recovered from the lungs, but a statistically significant increase in neutrophil counts for both summer and winter seasons in Westside. For the lung cytokine assays, the following patterns were observed:
Fresno summer: Significant decreases in IL-1β, IL-6 IL-10, INF-gamma, and MCP-1 were observed following CAPs exposure in lung homogenates.
Fresno winter: No significant changes were noted in the levels of cytokines in lung
homogenates following CAPs exposure compared with controls.
Westside summer: Demonstrated no statistically significant changes in cytokines following CAPs exposure.
Westside winter: Demonstrated significant increases in cytokine levels in lung homogenates for TNFa, IL-1a, IL-1b, IL-6, IL-12, GM-CSF, INF-gamma, MCP-1 and MIP-1a following
Supernatant from BAL is being analyzed for protein content and the presence of cytokines. In collaboration with the Wilson laboratory, optimal conditions for cytokine measurement are under way.
Lung tissues have been reoriented and embedded to enhance 1) airway analysis of central and distal airways. Staining is complete to examine for the presence and frequency of alcian blue/periodic acid Schiff (AB/PAS) positive airway epitheial cells.
With the completion of the first four CAPs studies for summer and winter seasons in both an urban and rural area of the San Joaquin Valley, we are now in the process of establishing potential relationships between biological responses observed and the emission sources for fine and ultrafine particles. Size-resolved particulate matter samples collected during each exposure experiment will be analyzed for organic molecular markers by extracting them with organic solvents followed by analysis using gas chromatography – mass spectrometry (GC-MS). The information obtained from this analysis will be combined with size-resolved source profiles to determine size-resolved source contributions to airborne particulate matter using the chemical mass balance (CMB) receptor model. The smallest size fraction analyzed will be 0.056-0.1 μm particle diameter (fully in the ultrafine size range).
Summary of Particle Size and Composition Fall and Winter Exposure Experiments in Fresno
Samples of airborne particulate matter were collected during September 4-9 and September 12-16, 2006 (late summer season) and again on February 13-17 and February 20-24, 2007 (winter season) using six Micro Orifice Uniform Deposit Cascade Impactors (MOUDIs) and three Reference Ambient Air Sampler (RAAS). Samples were collected for 6hrs each day during the animal exposure periods. Three of the MOUDIs were loaded with Teflon collection substrates (used for gravimetric, water soluble ions, and trace metals analysis) while the other three MOUDIs were loaded with Aluminum Foil substrates (used for gravimetric and carbon analysis). Upstream of each MOUDI a PM1.8 cyclone was used to remove coarse particles that might otherwise bounce off collection substrates. Six size fractions below 1.8 μm aerodynamic particle diameter were resolved with the MOUDI operated in this configuration. The RAAS sampler was equipped with multiple channels that employed Teflon filters and Quartz filters to characterize PM1.8 mass.
The PM1.8 mass collected during the Fresno summer event was 15.8 μg m-3 during September 4-9, 2006 and 18.8 μg m-3 during September 12-16, 2007. The PM1.8 mass collected during the Fresno winter event was 23.7 μg m-3 during February 13-17, 2007 and 11.0 μg m-3 during February 20-24, 2007. These concentrations are significantly lower than concentrations experienced during typical air pollution events in the SJV, when PM1.8 concentrations can increase to values greater than 100 μg m-3. Ultrafine (PM0.1) mass concentrations were measured to be 0.3-0.4 μg m-3 during all Fresno summer sampling events (summer and winter). PM0.1 concentrations greater than 2.0 μg m-3 have been measured during previous winter pollution events in the San Joaquin Valley. The low concentrations during the current study period are attributed to the weather conditions (atmosphere was well mixed during all days; rain was recorded at times).
The particle concentrator system can compensate for low ambient concentrations by increasing the exposure concentration by a factor of approximately 13. This will yield representative results during exposure experiments if the composition of the ambient particles is similar to the composition of particles during a true stagnation event. This assumes that the size and composition distribution of particles during the clean and polluted events are similar, but the absolute concentrations are lower during the clean event. The source apportionment of ultrafine particles during these periods of low concentrations will be very challenging and may not be possible if insufficient mass is available for analysis.
Figures 1 and 2 illustrate the size and composition distribution of particles collected during at Fresno during the summer and winter experiments, respectively.
Figure 1: Size and composition distribution of airborne particulate matter measured at Fresno during Sept 4-9, 2006 (week 1) and Sept 12-16, 2006 (week 2). The majority of the “unknown” material is likely common crustal components such as Si, Al, and Fe.
Figure 2: Size and composition distribution of airborne particulate matter measured at Fresno during Feb 13-17, 2007 (week 1) and Feb 20-24, 2007 (week 2).
Organic carbon, elemental carbon, and water soluble ions (sulfate, nitrate, etc) make up the majority of the particle size distribution during summer months. The Fresno sampling site was located in relatively close proximity to busy surface streets and highways in Fresno. It is expected that the majority of these particles are derived from tailpipe exhaust emissions and / or road dust sources. Nitrate contributions are strongly evident during winter months, when colder temperatures favor the partitioning of ammonium nitrate to the particle phase. Elemental analysis of these samples using ICPMS has been completed and the data is being reviewed for QA/QC.
Summary of Particle Size and Composition Fall and Winter Exposure Experiments in Westside
The PM1.8 mass concentrations measured at Westside were 9.4 μg m-3 during the summer experiment and 16.7 μg m-3 during the winter experiment. The PM0.1 concentrations measured at Westside were 0.5 μg m-3 during the summer experiment and 0.4 μg m-3 during the winter experiment. These concentrations are similar to those measured in the Fresno experiment, but since Westside is much further away from any direct emissions sources, it is expected that particles collected at this location have undergone significantly more atmospheric aging than particles collected at Fresno.
Figures 3 and 4 illustrate the size and composition distribution of particles collected at Westside during the summer and winter experiments, respectively.
Figure 3: Size and composition distribution of airborne particulate matter measured at Westside summer during week 1 and week 2. The majority of the “unknown” material is likely common crustal components such as Si, Al, and Fe.
Figure 4: Size and composition distribution of airborne particulate matter measured at Westside winter during week 1 and week 2.
Trends are qualitatively similar to those observed at Fresno. Carbonaceous aerosol dominates during the summer months, with the addition of ammonium nitrate during winter months. Source apportionment analysis will be used to quantify source contributions to primary carbonaceous aerosol.
We will identify the composition and size fraction of the airborne particles that cause adverse health effects in the San Joaquin Valley. The source origin of these unhealthy particles will be determined using source apportionment calculations. These findings will support an improved mechanistic understanding of how airborne particles cause negative health effects.
For the next reporting period, our plan are to (1) repeat the 10 day (2 week) CAPs study in Fresno for the summer and winter months, 2) create an allergic mouse model for incorporation into future CAPs studies, including the upcoming Fresno studies for the summer and winter seasons, and 3) acquire and configure a new larger trailer to allow more subjects in the field studies.
Background, rationale and plans for the ovalbumin allergic mouse model: Ovalbumin is a protein allergen that has been widely used in murine animals as a model of IgE-mediated allergic airway disease. Commonly the animals are sensitized to the allergen via intraperitoneal injection in the presence of an adjuvant, such as alum, and later challenged with an inhalation exposure of the allergen. Studies have revealed that local sensitization in the lung can be achieved through utilizing multiple intranasal instillations of the allergen. Further it has recently been illustrated that while fewer instillations of the allergen will not sensitize the animals, with instillate containing low levels of ultrafine particulate matter, an adjuvant effect is witnessed resulting in a sensitized animal. The PM Center is currently conducting research to validate these recent claims and to further investigate the adjuvant effect and its mechanism. Studies are being carried out which investigate the adjuvant effect through concomitant inhalation exposure to particulate matter with instilled allergen and instilled PM-enriched allergen to attempt to elucidate the mechanism of the particulate matter's adjuvant effect and determine its applicability to human exposures. Further research studies utilizing CAPs via the VACES exposure system will investigate the effects of atmospheric particles on both the sensitization and exacerbation of the allergic model in California's worst region of air pollution and asthma prevalence.
A pilot study to examine the adjuvant effects of particles on the ovalbumin model is underway using an iron/soot aerosol as a surrogate to San Joaquin Valley particles. The following exposure scenario has been implemented:
Work to acquire a second trailer for field studies is underway. This trailer will be larger in size compared with the current trailer to accommodate greater room for housing of animals, improve the environmental and housing conditions of the animals, facilitate working with the equipment and VACES system in the trailer, along with better lighting. Delivery is scheduled for September 17, 2008.
Cytokine analysis of BAL and lung tissues for Westside summer and winter CAPs studies will continue under the direction of Laurel Plummer. Further training is planning for Julian Recendez in filter preparation, instrument preparation and particle analysis for the upcoming summer 2008 Fresno CAPs study. Tentative dates for this study are August 18 to September 11.
on this Report
: 4 Displayed | Download in RIS Format
|| Donaldson K, Borm PJA, Oberdorster G, Pinkerton KE, Stone V, Tran CL. Concordance between in vitro and in vivo dosimetry in the proinflammatory effects of low-toxicity, low-solubility particles: the key role of the proximal alveolar region. Inhalation Toxicology 2008;20(1):53-62.
Abstract from PubMed
Full-text: SemanticScholar-Full Text PDF
|| Kleeman MJ, Riddle SG, Jakober CA. Size distribution of particle-phase molecular markers during a severe winter pollution episode. Environmental Science & Technology 2008;42(17):6469-6475.
Abstract from PubMed
Abstract: ACS Publications
|| Riddle SG, Robert MA, Jakober CA, Hannigan MP, Kleeman MJ. Size-resolved source apportionment of airborne particle mass in a roadside environment. Environmental Science & Technology 2008;42(17):6580-6586.
Abstract from PubMed
Full-text: ACS-Full Text HTML
Other: ACS-Full Text PDF
|| Smith KR, Veranth JM, Kodavanti UP, Aust AE, Pinkerton KE. Acute pulmonary and systemic effects of inhaled coal fly ash in rats: comparison to ambient environmental particles. Toxicological Sciences 2006;93(2):390-399.
Abstract from PubMed
Full-text: OUP-Full Text HTML
Other: OUP-Full Text PDF
cardiopulmonary, ultrafine particles, histology, immunohistochemistry, microassay, biology, pathology, physics, engineering, nanotechnology, metabolism, bioavailability, chemical mass balance model, ammonium, nitrates, sulfates, carbon, biochemistry, particulate matter, ambient air, ozone, sensitive populations, agriculture, transportation,
, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Risk Assessments, Physical Processes, ambient aerosol, lung injury, long term exposure, lung disease, acute cardiovascular effects, airway disease, exposure, airborne particulate matter, San Joaquin Valley, cardiac arrest, human exposure, inhalation, ambient particle health effects, PM, concentrated air particles, cardiovascular disease, human health risk
Progress and Final Reports:
2006 Progress Report
2007 Progress Report
2009 Progress Report
2010 Progress Report
Main Center Abstract and Reports:
San Joaquin Valley Aerosol Health Effects Research Center (SAHERC)
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832414C001 Project 1 -- Pulmonary Metabolic Response
R832414C002 Endothelial Cell Responses to PM—In Vitro and In Vivo
R832414C003 Project 3 -- Inhalation Exposure Assessment of San Joaquin Valley Aerosol
R832414C004 Project 4 -- Transport and Fate Particles
R832414C005 Project 5 -- Architecture Development and Particle Deposition