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Final Report: Southern California Particle Center and Supersite (SCPCS)

EPA Grant Number: R827352
Center: Southern California Particle Center and Supersite
Center Director: Froines, John R.
Title: Southern California Particle Center and Supersite (SCPCS)
Investigators: Froines, John R. , Arey, Janet , Atkinson, Roger , Avol, Edward L. , Berhane, Kiros , Charles, Judith M. , Cho, Arthur K. , Fukuto, Jon , Gauderman, William , Gong, Henry , Harkema, Jack , Hinds, William C. , Kleinman, Michael T. , Kumagai, Yoshito , Kunzli, Nino , Linn, William S. , Lurmann, Fred , McConnell, Rob , Miguel, Antonio , Nel, Andre E. , Peters, John M. , Phalen, Robert , Ritz, Beate R. , Schiestl, Robert H. , Sioutas, Constantinos , Stram, Dan , Turco, Richard , Winer, Arthur M. , Yu, Rong Chun
Institution: University of California - Los Angeles , Michigan State University , Rancho Los Amigos Medical Center , Sonoma Technology, Inc. , University of California - Davis , University of California - Irvine , University of California - Riverside , University of Southern California , University of Tsukuba
EPA Project Officer: Stacey Katz/Gail Robarge,
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
Project Amount: $8,715,583
RFA: Airborne Particulate Matter (PM) Centers (1999)
Research Category: Particulate Matter

Description:

Objective:

Southern California Particle Center and Supersite Overview

The overall objective of the Southern California Particle Center and Supersite (SCPCS) was to bring together outstanding scientists from the University of California–Los Angeles (UCLA), University of Southern California (USC), UC–Riverside, UC–Davis, UC–Irvine, Rancho Los Amigos Medical Center, Sonoma Technology, Michigan State University, and University of Tsukuba, Japan to identify and conduct high priority research to better understand exposure to and effects of airborne particulate matter (PM) and ensure protection of public health. Participating SCPCS faculty represented a wide range of disciplines including toxicology, epidemiology, biostatistics, immunology, pharmacology, medicine, atmospheric sciences, atmospheric and environmental chemistry, exposure assessment, and aerosol science.

The SCPCS developed an integrated approach to address the research needs in exposure, dosimetry, toxicology, and epidemiology of PM that were identified in the U.S. Environmental Protection Agency (EPA) Request for Application (RFA). SCPCS research included interaction and funding from the California Air Resources Board (CARB) and the South Coast Air Quality Management District (AQMD).

The Los Angeles Basin (LAB) is home to more than 14 million individuals who breathe some of the most polluted air in the U.S. The research projects in the SCPCS resulted in a detailed characterization of PM size, composition, and spatial variability across the LAB, applying measurement, analytical and modeling methodologies. Toxicology investigations were directed toward a fundamental understanding of the mechanisms and the chemical and physical components of PM responsible for health effects. Epidemiologic and human clinical studies provided new information to enhance our ability to detect human health effects from ambient air pollution. Given the continuing poor air quality in Southern California, it is unfortunate that a Center similar to SCPCS was not established years prior to 1999 (the commencement of the SCPCS). The need for this type of Center has not diminished. The SCPCS generated a wide range of projects and produced important findings and data within the themes and hypotheses that guided the overall research effort.

Summary/Accomplishments (Outputs/Outcomes):

Research Themes and Specific Projects

The principal theme of the SCPCS was: “Mobile Source Pollution and Health Effects.” All research within the SCPCS was intended to address specific priorities that had been articulated by the National Research Council (NRC) committee. The second theme that guided the research of the Center was: “Identification of the important physical/chemical characteristics of airborne PM responsible for the adverse health effects associated with PM and co-pollutant exposures.” A key feature of the research in the SCPCS was this linkage between exposure assessment/PM characterization and toxicological and human health outcomes. Health studies involved simultaneous physical and chemical characterization of the PM samples.

The SCPCS research programs were developed in three topic areas:

1. Studies emphasizing investigation of the biological mechanisms of PM effects in relation to PM physical and chemical characteristics
2. Studies of emission sources and related adverse health effects
3. Studies of the varying spatial and temporal patterns of ambient PM and co-pollutants and resulting health effects with a particular emphasis on the role of atmospheric chemistry

The studies in the SCPCS were conducted in the context of the secondary theme stated above, and one of the three general research areas. Research areas B and C were complementary and fundamentally linked with that in A. All three focused on the role of organic and metal constituents of PM, in accordance with our primary and secondary research themes. The research mission of the SCPCS was enhanced by the availability of ultrafine, fine, and coarse mobile concentrators which were essential for chemical toxicology, in vitro sample collection, in vivo studies, and human clinical studies and supported by the efforts of research core groups.

SCPCS Projects

This final report, covering each of the SCPC research themes, is presented as a series of individual reports from the 14 research projects listed below. In addition, there is a report from the dosimetry core on activities over the six year funding period, listed as project 16 (R827352C016) below.

Topic A: Investigation of the Biological Mechanisms of Particulate Matter (PM) Effects in Relation to PM Physical and Chemical Characteristics:

1. The Chemical Toxicology of Particulate Matter
2. Biological Effects of Diesel Exhaust Particulate and PM In Vivo and Iin Vitro
3. Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM
4. Effects of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
5. Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats

Topic B: Studies of Emission Sources and Adverse Health Effects:

6. Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
7. Exposure to Vehicular Pollutants and Respiratory Health
8. Traffic Density and Human Reproductive Health

Topic C: Studies of the Effects of Varying Spatial and Temporal Patterns of Ambient PM and Co-Pollutants and Resulting Health Effects With Emphasis on the Role of Atmospheric Chemistry:

9. The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and Other Atmospheric Transformation Products on Chronic Health Effects in Children: Exposure Assessment
10. A Novel Method for Measurement of Acrolein in Aerosols
11. Off-line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
12. Acute Cardiopulmonary Responses to Concentrated Ambient Particulate Matter in Human Volunteers
13. Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the Los Angles Basin
14. Physical and Chemical Characteristics of PM in the LAB: Source Receptor Study Exposure Assessment
15. Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS
16. Report on the Activities of the Dosimetry Core.

The project reports that follow detail the research the SCPCS has undertaken in investigation of these topical areas.

The following definitional/abbreviation convention is adopted throughout this document: F corresponds to airborne fine particulate matter (diameter <2.5 μm); C corresponds to airborne coarse particulate matter (diameter 2.5–10 μm); and UF corresponds to airborne ultrafine particulate matter (in most cases, particle diameter < 0.18 μm). The term accumulation mode is also used for F in some applications. Where the Sioutas concentrator is concerned, F represents the combination of F and UF particles (F + UF).

Topic A: Studies Emphasizing Investigation of the Biological Mechanisms of PM Effects in Relation to PM Physical and Chemical Characteristics

Project 1: The Chemical Toxicology of Particulate Matter (R827352C001)
Investigators: Arthur Cho, John Froines

Objective(s) of the Research Project: This project addressed the hypothesis that PM contains reactive chemical species and they, either separately or as a mixture, are responsible for the toxicological phenomena associated with PM. Reactive chemical species in PM can be organic or inorganic and act through several possible chemical reactions with biological substrates. To test our hypotheses, the project developed assays that can be applied to PM samples to assess their chemical reactivity and potential toxicity. Two of the assays measure redox activity, and have been developed and applied in several research studies. A third assay measures electrophilic chemistry of test substances, using a biological enzyme as a target. An assay for selected quinone species allows quantifying the levels of these compounds in ambient samples of particulate material on filters, in aqueous suspensions or as extracts containing volatile substances.

Summary of Findings: Key findings from this project include:

1. We determined the concentration of four quinones found in both particulate and volatile fractions of ambient air samples. The quantities of these quinones in diesel exhaust particles, the National Institute of Standards and Technology (NIST) standard, Standard Reference Material (SRM) 1649a, and in samples of ambient PM from the LAB were determined (Cho, et al., 2004), demonstrating their presence as well as the high variability found between days at the same site and between sites. Of the four quinones (1,2- and 1,4-naphthoquinone [1,2- and 1,4-NQ] and 9,10-phenanthroquinone [9,10-PQ] and 9,10-anthroquinone [9,10-AQ]), the NQs were found mostly in the volatile fraction of ambient air, whereas the three ring compounds PQ and AQ were found in the particulate fraction. The quantitative quinone assay was used to demonstrate changes in these highly reactive chemical species as an air mass moves across the LAB. The results are consistent with the notion that at least two of the quinones, 1,4-NQ and 9,10-PQ are formed by photochemical processes in the LAB. In a subsequent study, samples from a highway tunnel in northern California were analyzed, to assess a fresh emissions source. NQs were in relatively high concentrations in the volatile fraction whereas PQ and AQ were found in the particulate fraction.
2. The ability of PM to transfer electrons from dithiothreitol (DTT) to oxygen was used to develop a quantitative assay for redox properties (Cho, et al., 2005). Application of this assay to ambient PM samples indicated that activity in the assay correlated with the ability of sample to induce the stress related protein, hemeoxygenase-1 (HO-1) in a macrophage cell line (Li, et al., 2003). The studies of redox activity of air samples collected at different sites in the LAB found that while the activity per mass shows limited variability, the particle concentration range is such that exposure to redox active material can be highly variable at different sites and in different seasons. UF, in general, had greater potency in terms of redox activity per mass, while the greater mass concentration of F often renders this fraction responsible for the highest exposures to material active in the DTT assay. High activity was found in Claremont, an air pollution receptor site at which photochemical oxidation of PM constituents can occur.
3. We have found that samples of PM from roadways possess redox activity. In a study of the redox properties of diesel exhaust particles, we observed electron transfer capacity using both DTT and ascorbate as electron sources. The organic and acid extractable materials present in the particles possess redox activity but the particles retain significant activity after extraction.
4. The DTT based redox activity was shown to be due primarily to organic species, but metal ions, particularly from transition metals, also contribute to redox activity. To address this component, we measured the ability of PM samples to generate the Fenton chemistry product of salicylate, dihydroxybenzoic acid (DHBA). The relationship between activity in this assay and the DTT assay is being studied.
5. We have obtained preliminary evidence to support the notion that particles and their constituents exhibit electrophilic properties, as evidenced by the inhibition of the nucleophilic enzyme, glyceraldehyde phosphodehydrogenase (GAPDH).

Conclusions

This project has developed and applied several chemical assays that provide quantitative assessment of an activity associated with the toxicity of PM. The results of the application of these assays have allowed comparison of PM properties at different sites across the LAB and their relationship to cellular events associated with adverse health effects. As the characterization of PM using these assays develops further, the regulation of PM by content as it relates to potential toxicity may be possible. Our studies demonstrate that urban UFs exhibit greater potency in redox activity assays relative to larger size fractions of ambient PM, and this potency may be attributable to organic chemicals associated with combustion processes. Chemical properties that derive from the particle structure are relevant, and our DTT assay reflects the behavior of whole particles not limited to any specific constituent. Other research in the SCPCS found that cell biological effects of PM that are related to oxidative stress and mitochondrial damage are more highly related to UF exposure levels, indicating that activity in our chemical assays may predict biological toxicity of PM samples.

Project 2: Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro (R827352C002)
Investigators: Andre Nel, Ning Li, Constantinos Sioutas, Arthur Cho, John Froines

Objective(s) of the Research Project: The objective of this project was to develop an understanding of the mechanisms by which PM induces adverse health effects, with particular emphasis on the role particulates play in the promotion of asthma and cellular immune function.

Summary of Findings: Aim 1 was to elucidate the effects of diesel exhaust particulate (DEP) and ambient PM components on the generation of oxidative stress and inflammation in cellular studies performed in vitro. We demonstrated that DEP induces reactive oxygen species (ROS) production in macrophages and bronchial epithelial cells, and that these effects can be reproduced by methanol extracts made from these particles. ROS generation by pro-oxidative PM chemicals induced a hierarchical oxidative stress response in which a protective antioxidant defense (Tier 1) upgrades to pro-inflammatory (Tier 2) and cytotoxic effects (Tier 3) as the level of oxidative stress increases. An example of a Tier 1 antioxidant defense is the expression of HO-1. This gene is activated by the nuclear accumulation of Nrf2. This transcription factor drives the antioxidant response element (ARE) in the promoter of phase II enzymes, leading to increased expression of hemoxygenase-1, glutathione-S- transferase, NADPH quinone oxidoreductase, and catalase in DEP and PM-exposed macrophages and epithelial cells. HO-1, through its catabolic effect on heme, generates bilirubin and CO, which exerts antioxidant and cytoprotective effects. Escalation of oxidative stress to Tier 2, activates pro-inflammatory signaling pathways, e.g., the MAP kinase cascades. These cascades are involved in AP-1 transcriptional activity, leading to the expression of cytokines (e.g., IL-8) and adhesion molecules. At the highest level of oxidative stress (Tier 3), mitochondrial perturbation leads to the initiation of programmed cell death (apoptosis) and changes in mitochondrial morphology. Each tier of oxidative stress is sensitive to the effects of the thiol antioxidant, e.g., N-acetylcysteine.

An important extension was to investigate the role of specific redox cycling chemical groups, such as the polycyclic aromatic hydrocarbons (PAH) and quinones, in ROS generation. We performed silica gel chromatography on methylene chloride extracted DEP. After loading of the columns, aliphatic, aromatic and polar chemical fractions were eluted by increasing polar substances. We demonstrated that the quinone-enriched polar fraction was more active than the PAH-enriched aromatic fraction for its ability to redox cycle the DTT assay and to deplete glutathione in epithelial cells and macrophages. The aliphatic fraction was inactive in these assays. The relationship between the organic chemical composition and the redox cycling potential of PM was confirmed in a study where UF were compared to C and F collected in the LAB. UF were more active than C and F in the DTT assay, and also more effective in inducing oxidative stress in macrophages. Both the in vitro and cellular responses showed an excellent correlation with the PAH content of UF.

UF were found to lodge in mitochondria and disrupt the mitochondrial architecture. Functional effects on the permeability transition pore (PTP) and the mitochondrial membrane potential were confirmed in isolated mitochondrial preparations. Moreover, the UF effects on mitochondria could be reproduced by the polar and aromatic fractions prepared from DEP, while commercial nanoparticles were inactive. Together, these data show differential particle toxicity based on size, composition and subcellular localization.

Aim 2 was to use a murine model for asthma to study the effects of DEP on the enhancement of ovalbumin (OVA)-induced allergic inflammation and airway hyperreactivity (AHR). The asthma studies were premised on findings that DEP enhance allergen-specific IgE and TH2 cytokine production in humans and animals. We demonstrated that aerosolized DEP can enhance OVA-specific IgE production in a murine inhalation model. The adjuvant effect of DEP could be suppressed by NAC administration. While adequate for upregulating IgE production, an important limitation of this model was the inability of DEP to enhance AHR. This likely reflects the fact that oxidizing chemicals lead to efficient IgE gene rearrangement in deposition hotspots, but exposure did not exceed the threshold of airway inflammation that is required for AHR. DEP-induced AHR has now been achieved through modification of the classical mouse OVA sensitization model, in which sensitization is achieved by intraperitoneal administration of OVA. We developed two new protocols for OVA sensitization. In the low grade sensitization protocol, BALB/c mice received intraperitoneal OVA without alum, followed by challenge with aerosolized OVA ± DEP two weeks later. In the post-challenge model, DEP was delivered to classically sensitized animals a few days after the OVA challenge. Under both conditions, DEP enhanced airway inflammation to the point of exceeding the AHR threshold. Since these data suggest that low grade airway inflammation is required to elicit AHR, nebulized DEP was administered to mice which have been genetically engineered to overexpress IL-5. These animals exhibit constitutive airway inflammation, and responded to DEP inhalation with increased airway inflammation and AHR.

Conclusions

PM exerts prooxidative effects in tissue culture cells and in the immune system that can be ascribed to the presence of the redox cycling chemicals. The particles also play an important role by acting as a vehicle for the delivery of the prooxidative chemicals. The particle size is of particular importance in being able to localize in and perturb cellular immune function. The biology of oxidative stress involves different levels of cellular responses, in which there is a dynamic equilibrium between the protective antioxidant defenses and pro-inflammatory and cytotoxic cellular responses. This dynamic equilibrium determines whether the cellular and immunological impact will be subclinical or can lead to allergic inflammation and asthma.

Project 3: Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project) (R827352C003)
Investigators: Sheldon Friedlander, Constantinos Sioutas

Objective(s) of the Research Project: The ultrafine particle size range (dp < 0.1 μm) of the atmospheric aerosol is composed of both primary and secondary particulate matter. The primary component, emitted directly from sources, often includes agglomerates of 10 to 50 nm particles. (Note that the term “primary” in this context differs from its use to designate the individual particles that compose aerosol aggregate structures.) The secondary component is composed of particulate matter formed in the atmosphere, including sulfuric acid and sulfates, and organic reaction products of low volatility. Particles that form in the atmosphere tend to evaporate in the electron microscope, our principal observational method. Animal studies indicate that freshly formed agglomerate structures may have adverse health effects (Warheit, et al., 1990). Thus it is important to be able to characterize this component of the atmospheric aerosol.

With support from other sources, our Laboratory developed novel methods for the sampling and analysis of ultrafine atmospheric agglomerates. We applied our technology in a collaborative study with Dr. Constantinos Sioutas. Our goal was to determine whether the condensation and evaporation processes that precede aerosol concentration in the VACES alter the structure of agglomerates in the ultrafine particle size range. In the set of measurements described in methodology below, we found that the agglomerates were concentrated without substantial changes in their structure. The results of our study were described in the following publication:

Kim S, Jaques PA, Chang M, Barone T, Xiong C, Friedlander SK, Sioutas C. Versatile Aerosol Concentration Enrichment System (VACES) for simultaneous in vivo and in vitro evaluation of toxic effects of ultrafine, fine and coarse ambient particles. Part II: Field evaluation. Journal of Aerosol Science 2001;32(11):1299-1314.

Summary of Findings:

Methodology

Atmospheric ultrafine particles and those concentrated by the VACES were sampled using the low-pressure impactor (LPI) at the UCLA campus, in west Los Angeles. Measurements for the ambient air and concentrated particles from the VACES were made within minutes of each other. Concentrated ultrafine aerosols generated by the VACES were sampled after they were dried by diffusion. The LPI is an eight-stage single jet impactor equipped with a critical orifice that maintains a flow rate of 1 L/min under the appropriate pressure drop (Hering, et al., 1978; 1979). The stages have 50% efficiency cutoffs for aerodynamic diameters of 4.0, 2.0, 1.0, 0.5, 0.26, 0.11, 0.075, and 0.05 μm for stages one to eight, respectively. The particles were collected on a nickel transmission electron microscope (TEM) grid. To minimize the effects of particle bounce, only one stage at a time had a grid attached for sampling; the grid was secured at the center of a 25 mm diameter glass stage, while the other glass stages were coated with apiezon grease to trap the larger particles. Air was drawn through the impactor by a vacuum pump for 5 minutes per stage for aerosols coming from the concentrator and 10 minutes for the ambient air samples. Agglomerates were collected on LPI stages 7 and 8, which have aerodynamic diameter ranges of 0.075–0.11 μm and 0.05–0.075 μm, respectively. TEM photomicrographs of the grids were taken using a JEOL 100CX and 2000FX TEM at a magnification of 10⁵. To compare the morphologies of the atmospheric agglomerates and those concentrated by the VACES, we made use of fractal concepts. The fractal characteristics determine agglomerate transport and deposition from the atmosphere and in the lung. They may also affect the interaction of agglomerates with cellular surfaces. More details on fractal analysis conducted in our Laboratory can be found in Xiong (2000).

Experiments and computer simulations have shown that fractal concepts can often be applied to agglomerates of nanometer primary particles (Forrest and Witten, 1979; Witten and Sander, 1981). Such agglomerates can be described by the following relationship (Weber, et al., 1995):

(1)

where D_f is the fractal dimension, N_p is the number of primary particles in the agglomerate, A is the fractal pre-factor, R_o is the average primary particle radius and R_g is the radius of gyration. The radius of gyration is defined by the expression:

R_g = [(1/M)S(m_ir_i²)]^1/2 (2)

where mi is the mass of the i^th primary particle, M is the total mass given as ∑m_i, and r_i is the distance of the i^th primary particle from the center of mass. Values of D_f and A for agglomerates sampled from ambient air and from the concentrator exit air were obtained from a log-log plot of the number of primary particles as a function of distance from the center of mass to the edge of the agglomerate. The fractal dimension was determined from the slope of this diagram, and the prefactor from the intercept of the line representing the least squares fit.

Conclusions

Changes in agglomerate structure were investigated by comparing values for D_f and A for 38 agglomerates sampled from ambient air to 39 from the concentrator exit. Figures 1 and 2 show the D_f distributions for concentrated and ambient aerosols, respectively. The count median D_f was very similar (between 1.6 and 1.8) for both concentrated and ambient particles. The average value of A for the particles collected from the VACES was 2.73 and for the atmospheric agglomerates 2.83.

Figure 1. Fractal Dimension Distribution for Agglomerates From the VACES. The count mean D_f value was found to be between 1.8 and 2. Samples were taken at the Center for Health Sciences at UCLA on 8/22/00 using a LPI.

Figure 2. Fractal Dimension Distribution for Agglomerates Sampled From the Ambient Aerosol. The count mean D_f value was found to be between 1.6 and 1.8. Samples were taken at the Center for Health Sciences at UCLA on 8/22/00 using a LPI.

Previous studies suggest that chain agglomerates may become more compact when subjected to condensation and evaporation processes (Colbeck, et al., 1990; Hallet, et al., 1989; Wells, et al., 1976). In a study of diesel chain agglomerates (Huang, et al., 1994), the fractal dimension increased from 1.56 to 1.76 for mid-sulfur fuels and 1.40 to 1.54 for low-sulfur fuels, after condensation and evaporation processes. These were somewhat larger changes than we found. A possible explanation is that in the study by Huang, et al., the agglomerates underwent up to three cycles of condensation and evaporation while in our study they only went through one cycle. We therefore conclude that for the one set of measurements conducted by our Laboratory, the condensation and evaporation process used with the VACES did not cause significant changes in agglomerate structure as measured by D_f and A. However, both the sources of the fractal-like structures and associated trace gases may affect this phenomenon. Since the measurements were made for only one sampling site, more experiments will be needed at different sites to generalize these conclusions.

Project 4: Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model (R827352C004)
Investigators: Michael Kleinman, Constantinos Sioutas, Arthur Cho, John Froines

Objective(s) of the Research Project: The objective of this study was to examine the effects of exposure to concentrated ambient particles (CAPs) from a heavily trafficked freeway on biomarkers of allergic and inflammatory responses in an asthma mouse model. A secondary objective was to examine pro-inflammatory biomarkers in brain tissue as a preliminary approach to the hypothesis that exposure to particulate matter could play a role in the onset or progression of neurodegenerative disorders, some of which can display an increase in oxidative and inflammatory events. Development of the particle concentrators and animal work were supported by funding from the California Air Resources Board as part of a five year program to develop and apply PM concentrators in health studies. The SCPCS supported concentrator operations, physicochemical characterization of the CAPs to which animals were exposed, and the examination of pro-inflammatory markers in brain tissue.

Summary of Findings: The goal of this study was to test the following hypotheses: (1) exposure to mobile emissions from mobile sources close to a heavily trafficked roadway will exacerbate airway inflammation and allergic airway responses in a sensitized mouse model, and (2) the magnitude of allergic airway disease responses will decrease with increasing distance from the roadway. An ambient particle concentrator was used to expose ovalbumin (OVA)-treated BALB/c mice to purified air and to F and UF airborne particles at two distances, 50 m and 150 m, downwind of a roadway that is impacted by emissions from both heavy-duty diesel and light duty gasoline vehicles. Tissues and biological fluids from the mice were analyzed after exposures for 5 days per week in 2 consecutive weeks. The biomarkers of allergic or inflammatory responses that were assessed included cytokines released by Type 2 T-helper cells (IL-5, and IL-13), OVA-specific immunoglobulin E, OVA-specific immunoglobulin G1, and pulmonary infiltration of polymorphonuclear leukocytes and eosinophils. Allergy-related responses were increased in mice exposed to CAPs 50 m downwind of the road, compared to responses in mice exposed to purified air. No significant increases in allergy-related responses were observed in mice exposed to CAPs 150 m downwind of the road. The biological responses at the 50 m site were significantly associated with organic and elemental carbon components of F and UF suggesting that PM from motor vehicle fuel combustion could exert adjuvant effects and promote the development of allergic airway diseases.

We demonstrated that CAPs exposure increased inflammatory indices in the brains of ovalbumin-sensitized BALB/c mice. Animals were divided into three exposure groups: filtered air (control), UF, or F and UF. The levels of proinflammatory cytokines interleukin-1 alpha (IL-1α) and tumor necrosis factor alpha (TNF-α) in the cytoplasm of brain tissue preparations were measured by immunoassay, and found to be increased in samples from mice exposed to particulate matter compared to that of control animals. Levels of the transcription factor NF-κB, which plays an important role in the expression of many immune system and pro-inflammatory compounds were also found to be substantially elevated in the brains of exposed groups compared with those of mice in the control group, as measured by an electrophoretic mobility shift assay. These findings suggest that components of inhaled particulate matter may trigger a proinflammatory response in nervous tissue that could contribute to the pathophysiology of neurodegenerative diseases. This small scale study is notable in that it identifies an important potential target tissue for the toxicity of particulate matter that has received little attention to date. If present in humans, brain inflammatory responses to particulate matter exposure could have a significant public health impact.

A full report to the CARB on this study is available for public download at: http://www.arb.ca.gov/research/abstracts/98-316a.htm

Project 5: Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project) (R827352C005)
Investigator: Michael Kleinman

Objective(s) of the Research Project: A geriatric rat model was used to test the hypothesis that free radicals produced by reactive organic and inorganic constituents of motor vehicle exhaust particles will induce injury to lung epithelium and changes in heart rate and blood pressure in aged animals exposed to UF and F near a freeway.

Summary of Findings: This study was carried out in two phases. In Phase 1, twelve rats aged 22 to 24 months were exposed 6 hours per day for two consecutive days to F and UF CAPs at a site approximately 50 m downwind of a heavily trafficked freeway. The average exposure concentration was about 300 μg/m³. Control rats (n=10) were exposed to purified air. Four rats from the CAPs-exposure group were implanted with pressure transducers and transponders and their blood pressures and heart rates were measured. Measurements were made before and after each exposure. One of the implanted rats was euthanized because of a tumorous growth. Two weeks after the last CAPs exposure, the remaining implanted rats were exposed to purified air on 3 consecutive days, and blood pressure and heart rate were again measured before and after exposure.

Eight rats per group were euthanized 24 hours after their last exposure. Biochemical, cytological and histological assays were performed on blood, plasma, bronchoalveolar lavage, and heart and lung tissues. The endpoints included cell counts and cell differentials, inflammatory cytokines (TNFα, IL-1α, IL-1β, IFNγ) and anti-inflammatory cytokines (IL-4, IL-6, IL-10) in BAL. BAL from CAPs exposed animals had approximately 2 fold increases in some inflammatory and anti-inflammatory cytokines, relative to unexposed controls. IL-1α, IL-1β, IL-6 and IL-10 were increased in lung lavage fluid from exposed animals.

Heart rate and blood pressure were measured in the three surviving rats that had been implanted with cardiac monitors and telemetry transmitters. Average blood pressure and heart rate were both elevated when pre- and post-exposure measures were compared. The elevation in blood pressure after exposure was statistically significant, although the sample size is very small.

The surgical preparation of geriatric rats was difficult, and if scaled up, the protocol would benefit from implanting transmitters into rats at a younger age, before the exposure experiment was to commence. Notably, at a relatively low exposure concentration of F over just two days, we were able to detect post-exposure cardiovascular changes in three aged rats compared to controls and found some elevated cytokines in lavage fluid in a group of eight exposed animals.

A second exposure study was carried out in Phase 2. Thirty-four 22-month-old rats were exposed to filtered air (n=17) or PM_2.5 CAPs (n=17) at a site in Boyle Heights, CA with high levels of particulate pollution dominated by motor vehicle exhaust from freeway sources. Control group animals received filtered air. Blood pressure was obtained via tail cuff from all rats in the experiment. Electrocardiograph (ECG) parameters (heart rate [HR], heart rate variability [HRV]) and temperature were obtained from 5 animals in each group. Rats were monitored telemetrically for twenty minutes at the lab immediately before transport to the exposure site and twenty minutes at the lab immediately after the end of the exposure. Within 18–24 hours after the exposure ended, animals were euthanized by a lethal intraperitoneal injection of sodium pentobarbital (Nembutal, 65 mg/kg). Lung tissue samples were analyzed for malonaldehyde and glutathione as markers for oxidative stress, for IL-1β, TNFα, and IL-6, and for C-reactive protein. Western blots were analyzed for MAP kinases ERK1, ERK2, pERK2, JNK1, JNK2, p38 and pp38.

The concentration of CAPs ranged from 540–943 μg/m³ (mean: 655 μg/m³) at a site in Boyle Heights, CA with high levels of ambient particulate matter dominated by motor vehicle exhaust. With respect to cardiovascular responses, increased trends in the root mean square of successive differences in normal beat intervals (rMSSD) of HRV, a parameter highly correlated with vagal activity in the heart were observed on the second and third days of exposure. No significant exposure-related changes in blood pressure or heart rate were observed. The cytokine concentrations were not significantly different between control and exposed rats. All of the MAPK’s were lower in the exposed rats than in the control rats. The decreases were significant (p≤0.05) for ERK1 and pJNK. These MAPK’s are involved in protection of cells from apoptosis and further study of these parameters is warranted in future studies.

Topic B: Studies of Emission Sources and Related Adverse Health Effects

Project 6: Ultrafine Particles and Freeways (R827352C006)
Investigators: William Hinds, Yifang Zhu, Constantinos Sioutas

Objective(s) of the Research Project: It is now well established that increases in the concentration of fine particulate matter (PM_2.5) in urban areas are associated with increases in morbidity and mortality. It is not known what components of PM_2.5 cause these effects, but one candidate is the ultrafine particles (UF). These are particles less than 100 nm or 0.1 μm in size and are found near combustion sources, such as motor vehicles. In an urban environment motor vehicle emissions usually constitute the most important source of UF.

The overall objective of this research was to systematically evaluate and quantitatively predict UF particle concentration in the vicinity of freeways, particularly as they are transported downwind from freeways and into residences near freeways. Results from this study have provided data and tools that allow epidemiologists and toxicologists to estimate exposure to UF in the vicinity of major highways.

We made detailed measurements of UF near the 405 and 710 freeways, two of the busiest in the country. Interstate 405 carries more than 95% gasoline vehicles while Interstate 710 has up to 30% heavy-duty diesel vehicles. These freeways represent the range of vehicle mix one is likely to encounter in urban areas. Measurements were made in summer and in winter and during the day and at night to study the seasonal and diurnal variations of UF near freeways.

Particle number concentration and size distribution in the size range from 7 nm to 220 nm were measured by a condensation particle counter (CPC) and a scanning mobility particle spectrometer (SMPS), respectively. Measurements were taken at 30 m, 60 m, 90 m, 150 m, and 300 m downwind and 300 m upwind from Interstate highway 405 at the VA National Cemetery and at similar positions near Interstate 710. At each sampling point, the concentrations of carbon monoxide, black carbon and particle mass were also measured.

Summary of Findings: We found wind speed and direction, temperature, and relative humidity to be important factors in determining the local concentration of UF near freeways. The stronger the wind, the lower the total particle number concentration observed near freeways. The lower the temperature, or the higher the humidity, the higher the emission factor for UF especially for the primary mode particles below 30 nm. The maximum UF particle number concentration observed near freeways was about 25 times greater than background concentrations and decayed exponentially with downwind distance along the wind direction. Under the conditions of our measurements, CO, black carbon and particle number concentration track each other well with distance away from a freeway. Exponential decay was found to be a good estimator for the decrease in total particle number concentration with distance along the downwind direction. Strong seasonal and diurnal variations were found near freeways. Based on these experimental data, dispersion models and aerosol dynamic models were successfully developed that predict UF particle concentrations near freeways.

We also studied the penetration characteristics of freeway UF into nearby residences. Four two-bedroom apartments near the I-405 Freeway in Los Angeles, CA were selected for this study. Indoor (I) and outdoor (O) UF particle size distributions in the size range of 6 to 220 nm were measured simultaneously. We found significant amounts of freeway UF were able to penetrate into indoor environments. Particle number concentration I/O ratios showed strong dependence on particle sizes and were influenced by different ventilation mechanisms. Under natural ventilation, the highest I/O ratios (0.6–0.9) were usually observed for larger UF, while the lowest I/O ratios (0.1–0.4) occurred typically around 10–20 nm.

Project 7: Exposure to Vehicular Pollutants and Respiratory Health (R827352C007)
Investigators: Robert McConnell, Fred Lurmann, W. James Gauderman, Edward Avol

Objective(s) of the Research Project:

Project Hypotheses

This project tested the hypothesis that exposure to vehicular pollutants is associated with respiratory health outcomes in children. We have examined this hypothesis using data from the Children’s Health Study (CHS), a longitudinal evaluation originally designed to evaluate the effect of average community pollutant exposures on average community respiratory health outcomes. Pollution has been well characterized at central site monitors in 16 Southern California communities involving participants from two sets of school based cohorts. In the SCPCS we characterized within-community variation in traffic related particulate pollutant exposure and related traffic pollutants. These new pollutant metrics have allowed us to examine the relationship of individual level exposures to the CHS outcomes:

1. We developed modeled metrics of exposure and tested these against measured pollutants.
2. We evaluated the association of these metrics and of measured indicator pollutants to:
1. Prevalence and severity of asthma at entry
2. Incidence of asthma during follow-up
3. Lung function at study entry and its growth during follow-up
4. School absence.
3. We evaluated the association of chronic asthma exacerbation with chronic temporal variation from yearly variation in exposure to oxidant pollutants among asthmatics.

Project Objectives

Our approach was to geo-code addresses of residences and schools and then to assign traffic exposures to these addresses, based on traffic estimates available from the California Department of Transportation (Caltrans). We used ambient air quality measurements at 12 locations to evaluate these models. Using modifications of statistical modeling strategies developed for the CHS, we examined the effect of exposure to traffic related pollutants on asthma prevalence, and we found relationships not previously reported in this growing literature. In addition, we examined outcomes for which there has been little previous study of the effects of traffic modeled pollutants: asthma severity, asthma incidence, lung function and lung function growth, and school absence.

Summary of Findings: Some of the key findings of this project were:

1. Proximity to high traffic corridors and intra-community variability in traffic-related pollutants were associated with lifetime asthma in cross sectional analyses and with incident asthma during follow-up of the CHS cohorts.
2. Lung function and lung function growth were associated with traffic related air pollution estimated both at the home and at the central site monitor.
3. School absence was associated with traffic related air pollution at home and school among children with asthma.
4. Yearly variations in organic carbon and other particulate pollutants were strongly associated with bronchitis among children with asthma; these effects were modified by a dog in the home, an indicator of endotoxin exposure.

Project 8: Traffic Density and Human Reproductive Health (R827352C008)
Investigator: Beate Ritz

Objective(s) of the Research Project: This project proposed two research goals. The first goal was to determine whether residential proximity to heavy traffic roadways, such as freeways and major arterials, affected the risk of low birth weight (LBW) and preterm birth in infants born to women living in Los Angeles County, California between 1994–2000. Residential proximity to heavy traffic roadways was used as a surrogate measure of exposure to motor vehicle exhaust. The second research goal of this project was to evaluate whether maternal in-vehicle air pollutant exposures during commutes affected the risk of LBW and preterm birth in infants born to women living in Los Angeles County, California during 2003, who answered to a survey within 6 months of delivery.

Summary of Findings: First, we used an epidemiologic case-control study design to examine whether residential proximity to heavy-traffic roadways influenced the occurrence of LBW and/or preterm birth in Los Angeles County between 1994 and 1996 (Wilhelm and Ritz, 2003). We mapped subject home locations at birth and estimated exposure to traffic-related air pollution using a distance-weighted traffic density (DWTD) measure. The clearest exposure-response pattern was observed for preterm birth, with a risk ratio (RR) of 1.08 (95% confidence interval [CI]=1.01–1.15) for infants in the highest DWTD quintile. Although higher risks were observed for LBW infants, exposure-response relations were less consistent. Examining the influence of season, we found elevated risks primarily for women whose third trimester fell during fall/winter months (OR_{term LBW} = 1.39; 95% CI=1.16–1.67; OR_{preterm and LBW} = 1.24; 95% CI=1.03–1.48; RR_{all preterm} = 1.15; 95% CI=1.05–1.26) and exposure-response relations were stronger for all outcomes for these women. This result is consistent with elevated pollution in proximity to sources during more stagnant air conditions present in winter months.

In a second study (Wilhelm and Ritz, 2004), we expanded our analysis to the time period 1994–2000 and incorporated available information on the number of trucks frequenting freeways in our study area. We did not observe associations between DWTD and LBW (term and preterm) for 1997–2000, but in certain subgroups we still observed associations with preterm birth: women whose third trimesters fell primarily during fall/winter months (November–April) (RR=1.07, 95% CI = 0.99–1.16, comparing the highest to lowest DWTD quintile) and women living in census block groups with a fraction of children in poverty at or above the median value (RR=1.08; 95% CI=1.00–1.18). However, we observed a 23% greater risk of a preterm-LBW birth for women with ≥13,290 freeway trucks passing within 750 feet of their residence per day (95^th percentile) (OR=1.23, 95% CI=1.06–1.43) during 1997–2000.

In the work summarized above, we used electronic birth certificate data as the source of information on both health outcomes and other covariates we evaluated in our statistical models. However, the birth certificate data are missing information on some potentially important risk factors such as smoking, maternal stature and weight gain during pregnancy, and stress. We therefore conducted a nested case-control study in which we surveyed a sample of approximately 2,500 women in LA County (half of whom gave birth to a low weight or preterm infant) approximately four months after delivery to collect additional information on these factors (the survey was funded by the National Institute of Environmental Health Sciences [NIEHS]). As part of our survey, we asked women detailed information about their residential history and commuting habits during pregnancy. We calculated an average commute length and time for each woman who worked outside the home during pregnancy, weighting the distance (in miles and minutes) for each home by the time during pregnancy spent in each home. We observed a 47% increase in risk of delivering a preterm and LBW infant and a 55% increase in risk of delivering a LBW infant at term for women who commuted 45 minutes or more compared to those who commuted 5 minutes or less (OR=1.47, 95% CI=0.97–2.24 and OR=1.55, 95% CI=0.98–2.43, respectively). Adjustment for a number of important covariates did not change these estimates substantially.

In conclusion, we observed an approximately 10–20% increase in risk of preterm birth (both normal and low weight) and term LBW in infants born to women potentially exposed to high levels of traffic-related air pollution, as represented by DWTD when focusing on births during 1994–1996. These risks appeared to be strongest for women whose third trimester fell during fall/winter months, who lived in high background air pollution areas, and/or who lived in more impoverished areas according to census block-group level indicators of socioeconomic status (SES). Although residential proximity to traffic did not appear to be associated with higher risks of term LBW or preterm-LBW birth in the later time period included in this analysis (1997–2000), residential proximity to trucks on freeways did appear to be associated with greater risks of these outcomes, especially preterm-LBW, during 1997–2000. This suggests more heavily polluting vehicles within the overall cleaner motor vehicle fleet, such as trucks, may have become more important for these outcomes in the later years. Our finding of positive associations between ambient CO concentrations and term LBW, preterm-LBW birth, and preterm birth in 1997–2000 suggests, overall, air pollution may still be harmful. We feel a more refined exposure assessment approach is needed at this point to arrive at further conclusions concerning the associations between residential proximity to traffic and the adverse birth outcomes we have seen in our studies. One approach would be to develop an individual exposure model that takes into account exposure to indoor sources of air pollution and in-vehicle exposures, in addition to residential exposures to outdoor air pollution by accounting for concentrations within each of these microenvironments and time-activity patterns of pregnant women. Measurements of key traffic-related pollutants (CO, NO₂, UF) inside a sample of Los Angeles homes with varying levels of traffic in close proximity would provide needed information about typical at-home exposures and the influence of indoor pollution sources to overall exposure. Our results also indicate that in-vehicle exposures to air pollution while commuting during pregnancy may be important for low birth weight. We plan to analyze these data further and take into consideration the importance of type of commute (e.g., car versus bus, freeway versus surface streets), whether commuting distances vary by pregnancy period and if yes, the importance of this variation to the outcomes of interest, the importance of car age, and the importance of total time spent in a car including other in-vehicle activities besides commuting to work.

Topic C: Studies of the Effects of Varying Spatial and Temporal Patterns of Ambient PM and Co-pollutants and Resulting Health Effects with Emphasis on the Role of Atmospheric Chemistry

Project 9: The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children (R827352C009)
Investigators: Edward Avol, Antonio Miguel, Arthur Cho, John Froines

Objective(s) of the Research Project: The two primary objectives guiding the sampling study were: (1) to develop an estimate of seasonal variability and annual levels of specific ambient aldehydes, quinones, and polycyclic aromatic hydrocarbons (PAH) in the 12 communities under study in the USC Children’s Health Study (CHS), and (2) to assess the possible association of those estimates with observed CHS health outcomes. The core studies of the CHS were funded primarily by CARB, and full final reports can be found at: http://www.arb.ca.gov/research/chs/chs.htm .

Summary of Findings: Using an innovative sampler deployment approach to collect seasonal samples in 12 sampling locations with only three sets of instrumentation, field sampling was successfully performed in consecutive two-month deployments across all 12 CHS communities between 2001 and 2003. In the course of field operations, an improved sampling matrix was developed to successfully capture and stabilize particle and vapor-phase PAHs, aldehydes, and quinones in a multiple-media sampling matrix for 24 hr sampling intervals. Variability in inter-community levels of PAHs, carbonyls, and quinones was observed, with apparent phase shifts between vapor and particles as the result of ambient temperature.

Conclusions

Ambient air samples were collected in 12 Southern California communities to assess seasonal variability and annual estimates of 15 PAHs, four quinones, and 15 aldehydes of environmental and health concern. Analyses revealed that:

1. Virtually all of the total PAH mass was found in the vapor-phase and vapor phase PAHs were dominated by naphthalene.
2. Vapor-phase PAH concentrations were essentially uncorrelated with those of the more commonly measured pollutants (O₃, NO₂, PM₁₀, elemental carbon [EC], organic carbon [OC], ambient acids).
3. Several particle-phase PAHs and aldehydes were strongly correlated with more commonly measured pollutants (O₃, NO₂, PM₁₀, EC, OC, ambient acids).
4. Particle-phase PAH levels were similar across most of the study sites.
5. Particle-phase PAH levels were 2 to 54 times higher in winter than summer.
6. Particle-phase PAH concentrations were negatively correlated with mean air temperature.
7. In two-pollutant models assessing decrements in lung function growth rate indices (FEV₁ and MMEF), the PAH, aldehyde, and quinone constituents of PM did not generally provide additional clarification in the health analyses over NO₂ or PM_2.5.

Project 10: Novel Method for Measurement of Acrolein in Aerosols (R827352C010)
Investigator: Judith M. Charles

Objective(s) of the Research Project:

Hypothesis

The overall objective of the project is to develop a method to measure acrolein, and other carbonyls that either are directly emitted from motor vehicles or are photooxidation products of hydrocarbons in motor vehicle exhaust (e.g., crotonaldehyde, hydroxyl acetone, glycolaldehyde, methyl glyoxal, glyoxal) that is accurate and precise, and that affords a short sampling time.

Objectives

The objective of this project was to develop a new method to measure acrolein and other toxic carbonyls in air that affords part-per-trillion detection limits and short sampling times (10 minutes). The proposed method relies on using a mist chamber to sample carbonyls, followed by detection of the compounds by using derivatization along with gas chromatography/mass spectrometry (GC/MS).

Summary of Findings: Initial work was conducted to explore whether carbonyls could be sampled into a mist chamber by using an aqueous bisulfite solution, and whether the carbonyls could be analyzed by releasing the carbonyl-bisulfite adduct and then derivatizing the “free” carbonyl with 0-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine (PFBHA) prior to detection by using gas chromatography/mass spectrometry. Specifically, experiments were conducted to: 1) establish the formation of carbonyl-bisulfite adducts by measuring the formation constants (k_f) for formaldehyde, methyl glyoxal, acrolein, glyoxal, methacrolein, crotonaldehyde, hydroxy acetone and glycolaldehyde, 2) investigate the effect of pH on PFBHA derivatization of the carbonyls in the presences and absence of bisulfite, and 3) investigate the effect of bisulfite concentration on PFBHA derivatization. Once optimum conditions were determined for formation and derivatization of the carbonyls, we compared the collection efficiency (CE) in the mist chamber using an aqueous solution, a 0.001M bisulfite solution, a 2mM PFBHA solution and a 2mM pentafluorophenylhydrazine (PFPH) solution. The collection efficiency is a measure of the efficiency of the mist chamber to capture the carbonyls is the first mist chamber, using 2 mist chambers in series.

The k_f of the carbonyls were determined at pH=5.0 using pseudo-first order kinetics. The k_f for formaldehyde was 15.15 ± 1.36 M^-1s^-1 which is in close agreement with the literature value of 12.83 M^-1s^-1, thereby validating the analytical approach. The formation constant for acrolein was 0.73 ± 0.10 M^-1s^-1 with a 96% yield in 10 minutes. These k_fs and the k_fs obtained for the other compounds establish the formation of carbonyl-bisulfite adducts at pH=5.0 with >80% yields in 10 minutes. Since samples will be collected in the field, and then prepared for analysis in the laboratory, we also explored the stability of the bisulfite adducts over a 6 day period. The effect of pH on PFBHA derivatization was explored at pH=1, 5 and 12 in the absence of bisulfite. The results were consistent with previous data that demonstrate that PFBHA derivatization occurs at neutral and acidic, but not basic pH. The experiment was repeated at pH=5.0 in the presence of 0.05 M bisulfite. The concentration of the PFBHA derivatives was lower in the presence of bisulfite than in the absence of bisulfite, indicating that the bisulfite hinders PFBHA derivatization of the carbonyls. Further experiments established that derivatization was also compromised at 0.005 M and 0.001 M bisulfite concentrations, with higher concentrations of derivatives being formed at the lowest bisulfite concentration. The finding that bisulfite hinders or interferes with PFBHA derivatization was significant and may be a deterrent to using an aqueous solution bisulfite as the collecting medium in the mist chamber. Comparison of the collection efficiency for acrolein, methacrolein, methyl vinyl ketone, crotonaldehyde, glyoxal and methyl glyoxal using water, a 0.001 M bisulfite solution, a 2 mM PFBHA solution and a 2 mM PFPH solution demonstrated this occurrence. Overall the collection efficiency followed the order of water < PFBHA solution < 0.00 1M bisulfite solution < PFPH solution. For example for acrolein, the collection efficiency in water, a 0.001 M bisulfite solution, a 2 mM PFBHA solution and a 2 mM PFPH solution was 0.18±0.04, 0.448±0.13, 0.19±0.07, and 0.89±0.07, respectively. The reason that the collection efficiency for PFPH is higher than PFBHA is not clear, but may be due to greater water solubility and lower volatility of the hydrazone derivatives, and faster and more expedient derivatization of the carbonyls using PFBHA compared to PFPH (see Figure 3).

Figure 3. Comparison of Collection Efficiencies of Acrolein and Other Carbonyls Using Different Solutions in a Mist Chamber

In view of the established k_f for the carbonyls, and the water-solubility and stability of the carbonyl-bisulfite adducts, the lower collection efficiency in the presence of the bisulfite solution compared to using PFPH is likely a result of poor derivatization of the carbonyls with PFBHA in the presence of bisulfite. The difference between the collection efficiency when water is used as the collection media vs. an aqueous solution of PFPH indicates that formation of the derivatives is critical to efficiently capturing the carbonyls.

Previous research conducted in our laboratory demonstrates the ability of a 2 mM solution in a mist chamber to sample carbonyls with Henry’s law constants < 10³. To sample less polar carbonyls, such as acrolein, a 0.001 M bisulfite or a 2 mM PFPH solution can be used. Although the use of the bisulfite solution to collect the carbonyls and form carbonyl-bisulfite adducts is an attractive approach due to the water solubility of carbonyl-bisulfite adducts, PFBHA derivatization of the carbonyls is hindered in the presence of S(IV). For this reason, if bisulfite is used in the mist chamber to collect the carbonyls, we suggest that further research be conducted to investigate the direct detection of the carbonyl-bisulfite adducts. The high collection efficiencies for acrolein (CE=8.0), and overall good collection efficiency (CE > ~6.0) for methacrolein, methyl vinyl ketone, crotonaldehyde, glyoxal and methyl glyoxal using a 2 mM PFPH solution in the mist chamber indicates that use of PFPH along with detection by using GC/MS will afford sensitive detection of acrolein and other toxic carbonyls.

Project 11: Off-line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys (R827352C011)
Investigators: Henry Gong, William Linn

Objective(s) of the Research Project: Delayed offline measurement of exhaled nitric oxide (eNO) has important applications in environmental health screening studies where direct online measurement can be impractical. However, the use and application of delayed offline eNO has been limited by the instability of stored breath samples. Our goal was to develop a practical method for off-line measurement of eNO that can be applied in larger multiple-site epidemiologic surveys, with reliable preservation of exhaled breath samples for analysis at one central laboratory.

Summary of Findings:

Description of Research

Exploratory experiments indicated that breath could be collected satisfactorily in commercial eNO sampling bags (Sievers Instruments, Boulder, CO) or in structurally similar toy balloons made of aluminized polyethylene terephthalate film (Mylar or equivalent). We used both sampling bags and balloons with a Bag Collection and Sampling Kit (Sievers Instruments) that allowed a subject to take a vital-capacity inspiration of relatively NO-free air and immediately exhale it at a measured flow rate near 100 mL/sec. Exhaled air was allowed to escape for the first 3–6 sec to clear deadspace, then a sample of 0.5 to 1.5 L was collected. After preliminary experiments to optimize the procedure, we obtained 185 air samples, including:

• breath from 38 nonsmoking volunteer subjects (10 adults, 22 high school students, and 6 children aged 9–13, including individuals with asthma or other chronic cardiorespiratory conditions),
• ambient air over a range of NO pollution conditions,
• air filtered by the breath collection apparatus (like the air inhaled by subjects during tests), and
• commercial zero air free of NO.

Samples were collected in our laboratory and at 5 field locations (3 schools, 2 homes) in
metropolitan Los Angeles. Each sample was measured repeatedly with a chemiluminescent NO analyzer (Sievers NOA Model 280i) over a period of 1–7 days. A calibration check with zero and span gas was performed within 20 min of each sample measurement. Samples were stored at 42, 22, 6, or -14 degrees Celsius to

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Type	Citation	Sub Project	Document Sources
Journal Article	Arellanes C, Paulson SE, Fine PM, Sioutas C. Exceeding of Henry’s Law by hydrogen peroxide associated with urban aerosols. Environmental Science & Technology 2006;40(16):4859-4866.	R827352 (Final)	Abstract from PubMed Full-text: ACS Publications Full Text Abstract: ACS Publications Abstract Other: ACS Publications PDF
Journal Article	Arhami M, Kuhn T, Fine PM, Delfino RJ, Sioutas C. Effects of sampling artifacts and operating parameters on the performance of a semicontinuous particulate elemental carbon/organic carbon monitor. Environmental Science & Technology 2006;40(3):945-954.	R827352 (Final)	Full-text: ACS Publications Full Text Abstract: ACS Publications Abstract Other: ACS Publications PDF
Journal Article	Becker S, Soukup JM, Sioutas C, Cassee FR. Response of human alveolar macrophages to ultrafine, fine, and coarse urban air pollution particles. Experimental Lung Research 2003;29(1):29-44.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Biswas S, Fine PM, Geller MD, Hering SV, Sioutas C. Performance evaluation of a recently developed water-based condensation particle counter. Aerosol Science and Technology 2005;39(5):419-427.	R827352 (Final) R827352C014 (Final)	Abstract: InformaWorld Abstract Other: InformaWorld PDF
Journal Article	Campbell A, Oldham M, Becaria A, Bondy SC, Meacher D, Sioutas C, Misra C, Mendez LB, Kleinman M. Particulate matter in polluted air may increase biomarkers of inflammation in mouse brain. Neurotoxicology 2005;26(1):133-140.	R827352 (2004) R827352 (Final) R827352C005 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Chakrabarti B, Singh M, Sioutas C. Development of a near-continuous monitor for measurement of the sub-150 nm PM mass concentration. Aerosol Science and Technology 2004;38(Suppl 1):239-252.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: University of Southern California PDF
Journal Article	Chakrabarti B, Fine PM, Delfino R, Sioutas C. Performance evaluation of an active-flow personal DataRAM PM2.5 mass monitor (Thermo Anderson pDR-1200) designed for continuous personal exposure measurements. Atmospheric Environment 2004;38(20):3329-3340.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Chan RC-F, Wang M, Li N, Yanagawa Y, Onoe K, Lee JJ, Nel AE. Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation. Journal of Allergy and Clinical Immunology 2006;118(2):455-465.	R827352 (Final) R827352C002 (Final) R832413 (2008) R832413C002 (2007) R832413C002 (2008)	Abstract from PubMed Full-text: ScienceDirect Other: ScienceDirect PDF
Journal Article	Chang M, Sioutas C, Cassee FR, Fokkens PHB. Field evaluation of a mobile high-capacity particle size classifier (HCPSC) for separate collection of coarse, fine and ultrafine particles. Journal of Aerosol Science 2001;32(1):139-156.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Chang M-C, Geller MD, Sioutas C, Fokkens PHB, Cassee FR. Development and evaluation of a compact, highly efficient coarse particle concentration for toxicological studies. Aerosol Science and Technology 2002;36(4):492-501.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Cho AK, Di Stefano E, You Y, Rodriquez CE, Schmitz DA, Kumagai Y, Miguel AH, Eiguren-Fernandez A, Kobayashi T, Avol E, Froines JR. Determination of four quinones in diesel exhaust particles, SRM 1649a and atmospheric PM2.5. Aerosol Science and Technology 2004;38(Suppl 1):68-81.	R827352 (Final) R827352C001 (Final) R827352C009 (Final) R827352C013 (Final) R831861 (2004) R831861 (2005)	Abstract: Ingenta Connect Abstract Other: Childrens Centers PDF
Journal Article	Cho AK, Sioutas C, Miguel AH, Kumagai Y, Schmitz DA, Singh M, Eiguren-Fernandez A, Froines JR. Redox activity of airborne particulate matter at different sites in the Los Angeles Basin. Environmental Research 2005;99(1):40-47.	R827352 (Final) R827352C001 (Final) R827352C013 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Science Direct Abstract Other: Science Direct PDF
Journal Article	Cui Y, Zhang Z-F, Froines J, Zhao J, Wang H, Yu S-Z, Detels R. Air pollution and case fatality of SARS in the People’s Republic of China: an ecologic study. Environmental Health 2003;2(1):15.	R827352 (2004) R827352 (Final)	Abstract from PubMed Full-text: Environmental Health Full Text Other: Environmental Health PDF
Journal Article	de Pereira PA, de Andrade JB, Miguel AH. Determination of 16 priority polycyclic aromatic hydrocarbons in particulate matter by HRGC-MS after extraction by sonication. Analytical Sciences 2001;17(10):1229-1231.	R827352 (Final) R827352C013 (Final)	Abstract from PubMed Other: The Japan Society for Analytical Chemistry PDF
Journal Article	de Pereira PA, de Andrade JB, Miguel AH. Measurements of semivolatile and particulate polycyclic aromatic hydrocarbons in a bus station and an urban tunnel in Salvador, Brazil. Journal of Environmental Monitoring 2002;4(4):558-561.	R827352 (2004) R827352 (Final) R827352C013 (Final)	Abstract from PubMed
Journal Article	De Vizcaya-Ruiz A, Gutierrez-Castillo ME, Uribe-Ramirez M, Cebrian ME, Mugica-Alvarez V, Sepulveda J, Rosas I, Salinas E, Garcia-Cuellar C, Martinez F, Alfaro-Moreno E, Torres-Flores V, Osornio-Vargas A, Sioutas C, Fine PM, Singh M, Geller MD, Kuhn T, Miguel AH, Eiguren-Fernandez A, Schiestl RH, Reliene R, Froines J. Characterization and in vitro biological effects of concentrated particulate matter from Mexico City. Atmospheric Environment 2006;40(Suppl 2):583-592.	R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Delfino RJ, Sioutas C, Malik S. Potential role of ultrafine particles in association between airborne particle mass and cardiovascular health. Environmental Health Perspectives 2005;113(8):934-946.	R827352 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Doherty SP, Prophete C, Maciejczyk P, Salnikow K, Gould T, Larson T, Koenig J, Jaques P, Sioutas C, Zelikoff JT, Lippmann M, Cohen MD. Detection of changes in alveolar macrophage iron status induced by select PM2.5-associated components using iron-response protein binding activity. Inhalation Toxicology 2007;19(6-7):553-562.	R827352 (Final) R827351 (Final) R827355 (2004) R827355 (Final)	Abstract from PubMed Abstract: InformaWorld Abstract
Journal Article	Eiguren-Fernandez A, Miguel AH. Determination of semivolatile and particulate polycyclic aromatic hydrocarbons in SRM 1649a and PM2.5 samples by HPLC-fluorescence. Polycyclic Aromatic Compounds 2003;23(2):193-205.	R827352 (2004) R827352 (Final) R827352C013 (Final)	Abstract: Informa World Abstract
Journal Article	Eiguren-Fernandez A, Miguel AH, Jaques PA, Sioutas C. Evaluation of a denuder-MOUDI-PUF sampling system to measure the size distribution of semi-volatile polycyclic aromatic hydrocarbons in the atmosphere. Aerosol Science and Technology 2003;37(3):201-209.	R827352 (2004) R827352 (Final) R827352C013 (Final) R827352C014 (Final)	Full-text: Informa World Full Text Abstract: Informa World Abstract
Journal Article	Eiguren-Fernandez A, Miguel AH, Froines JR, Thurairatnam S, Avol EL. Seasonal and spatial variation of polycyclic aromatic hydrocarbons in vapor-phase and PM2.5 in Southern California urban and rural communities. Aerosol Science and Technology 2004;38:447-455.	R827352 (2004) R827352 (Final) R827352C009 (Final) R827352C013 (Final) R831861 (2005)	Full-text: Informa World Full Text Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Eiguren-Fernandez A, Avol EL, Thurairatnam S, Hakami M, Froines JR, Miguel AH. Seasonal influence on vapor- and particle-phase polycyclic aromatic hydrocarbon concentrations in school communities located in Southern California. Aerosol Science and Technology 2007;41(4):438-446.	R827352 (Final) R827352C009 (Final) R827352C013 (Final) R832413 (2008) R832413C003 (2007) R832413C003 (2008)	Full-text: InformaWorld Abstract: InformaWorld Other: InformaWorld PDF
Journal Article	Eiguren-Fernandez A, Miguel AH, Lu R, Purvis K, Grant B, Mayo P, Di Stefano E, Cho AK, Froines J. Atmospheric formation of 9,10-phenanthraquinone in the Los Angeles air basin. Atmospheric Environment 2008;42(10):2312-2319.	R827352 (Final) R832413 (2007) R832413 (2008) R832413C003 (2007) R832413C003 (2008)	Full-text: ScienceDirect Abstract: ScienceDirect Other: ScienceDirect PDF
Journal Article	Fine PM, Jaques PA, Hering SV, Sioutas C. Performance evaluation and use of a continuous monitor for measuring size-fractionated PM2.5 nitrate. Aerosol Science and Technology 2003;37(4):342-354.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Fine PM, Chakrabarti B, Krudysz M, Schauer JJ, Sioutas C. Diurnal variations of individual organic compound constituents of ultrafine and accumulation mode particulate matter in the Los Angeles Basin. Environmental Science & Technology 2004;38(5):1296-1304.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Fine PM, Shen S, Sioutas C. Inferring the sources of fine and ultrafine particulate matter at downwind receptor sites in the Los Angeles Basin using multiple continuous measurements. Aerosol Science and Technology 2004;38(S1):182-195.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Fruin SA, St Denis MJ, Winer AM, Colome SD, Lurmann FW. Reductions in human benzene exposure in the California South Coast Air Basin. Atmospheric Environment 2001;35(6):1069-1077.	R827352 (2004) R827352 (Final) R827352C015 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Gauderman WJ, Avol E, Lurmann F, Kuenzli N, Gilliland F, Peters J, McConnell R. Childhood asthma and exposure to traffic and nitrogen dioxide. Epidemiology 2005;16(6):737-743.	R827352 (Final) R827352C007 (Final) R827352C009 (Final) R831861 (2004) R831861 (2005) R831861C001 (2005)	Abstract from PubMed
Journal Article	Gauderman WJ, Vora H, McConnell R, Berhane K, Gilliland F, Thomas D, Lurmann F, Avol E, Kunzli N, Jerrett M, Peters J. Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study. The Lancet 2007;369(9561):571-577.	R827352 (Final) R827352C007 (Final) R831861 (2005)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Geller MD, Kim S, Misra C, Sioutas C, Olson BA, Marple VA. A methodology for measuring size-dependent chemical composition of ultrafine particles. Aerosol Science and Technology 2002;36(6):748-763.	R827352 (2004) R827352 (Final) R827352C014 (Final) R828678C009 (2002)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Geller MD, Fine PM, Sioutas C. The relationship between real-time and time-integrated coarse (2.5-10 μm), intermodal (1-2.5 μm), and fine (<2.5 μm) particulate matter in the Los Angeles Basin. Journal of the Air & Waste Management Association 2004;54(9):1029-1039.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract from PubMed Other: University of Southern California PDF
Journal Article	Geller MD, Sardar SB, Phuleria H, Fine PM, Sioutas C. Measurements of particle number and mass concentrations and size distributions in a tunnel environment. Environmental Science & Technology 2005;39(22):8653-8663.	R827352 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: ACS Full Text Other: ACS PDF
Journal Article	Geller MD, Ntziachristos L, Mamakos A, Samaras Z, Schmitz DA, Froines JR, Sioutas C. Physicochemical and redox characteristics of particulate matter (PM) emitted from gasoline and diesel passenger cars. Atmospheric Environment 2006;40(36):6988-7004.	R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Geller M, Biswas S, Sioutas C. Determination of particle effective density in urban environments with a differential mobility analyzer and aerosol particle mass analyzer. Aerosol Science and Technology 2006;40(9):709-723.	R827352 (Final)	Full-text: InformaWorld Full Text Abstract: InformaWorld Abstract Other: InformaWorld PDF
Journal Article	Gong H, Sioutas C, Linn WS, Clark KW, Terrell SL, Terrell LL, Anderson KR, Kim S, Chang M-C. Controlled human exposures to concentrated ambient fine particles in metropolitan Los Angeles: methodology and preliminary health-effect findings. Inhalation Toxicology 2000;12(1):107-119.	R827352 (2004) R827352 (Final) R827352C012 (Final) R827352C014 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final)	Abstract: Informa World Abstract
Journal Article	Gong H Jr, Linn WS, Sioutas C, Terrell SL, Clark KW, Anderson KR, Terrell LL. Controlled exposures of healthy and asthmatic volunteers to concentrated ambient fine particles in Los Angeles. Inhalation Toxicology 2003;15(4):305-325.	R827352 (2004) R827352 (Final) R827352C012 (Final) R827352C014 (Final) R831861 (2005)	Abstract from PubMed
Journal Article	Gong H Jr, Linn WS, Terrell SL, Clark KW, Geller MD, Anderson KR, Cascio WE, Sioutas C, Cascio WE, Sioutas C. Altered heart-rate variability in asthmatic and healthy volunteers exposed to concentrated ambient coarse particles. Inhalation Toxicology 2004;16(6-7):335-343.	R827352 (2004) R827352 (Final) R827352C012 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Gong H Jr, Linn WS, Terrell SL, Anderson KR, Clark KW, Sioutas C, Cascio WE, Alexis N, Devlin RB. Exposures of elderly volunteers with and without chronic obstructive pulmonary disease (COPD) to concentrated ambient fine particulate pollution. Inhalation Toxicology 2004;16(11-12):731-744.	R827352 (2004) R827352 (Final) R827352C012 (Final) R827352C014 (Final) R827999 (Final) R831861 (2005)	Abstract from PubMed
Journal Article	Gong H Jr, Linn WS, Clark KW, Anderson KR, Geller MD, Sioutas C. Respiratory responses to exposures with fine particulates and nitrogen dioxide in the elderly with and without COPD. Inhalation Toxicology 2005;17(3):123-132.	R827352 (Final) R827352C012 (Final) R827352C014 (Final) R827999 (Final) R831861 (2005)	Abstract from PubMed Other: USC PDF
Journal Article	Gong Jr. H, Linn WS, Clark KW, Anderson KR, Sioutas C, Alexis NE, Cascio WE, Devlin RB. Exposures of healthy and asthmatic volunteers to concentrated ambient ultrafine particles in Los Angeles. Inhalation Toxicology 2008;20(6):533-545.	R827352 (Final) R832413 (2007) R832413 (2008) R832413C001 (2007) R832413C001 (2008)	Abstract from PubMed
Journal Article	Hao M, Comier S, Wang M, Lee JJ, Nel A. Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models. Journal of Allergy and Clinical Immunology 2003;112(5):905-914.	R827352 (2004) R827352 (Final) R827352C002 (Final)	Abstract from PubMed Other: Science Direct PDF
Journal Article	Hasson AS, Paulson SE. An investigation of the relationship between gas-phase and aerosol-borne hydroperoxides in urban air. Journal of Aerosol Science 2003;34(4):459-468.	R827352 (2004) R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Hering S, Fine PM, Sioutas C, Jaques PA, Ambs JL, Hogrefe O, Demerjian KL. Field assessment of the dynamics of particulate nitrate vaporization using differential TEOM and automated nitrate monitors. Atmospheric Environment 2004;38(31):5183-5192.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Hiura TS, Li N, Kaplan R, Horwitz M, Seagrave J-C, Nel AE. The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles. Journal of Immunology 2000;165(5):2703-2711.	R827352 (2004) R827352 (Final) R827352C002 (Final)	Abstract from PubMed Full-text: Journal of Immunology Full Text Other: Journal of Immunology PDF
Journal Article	Hiyoshi K, Takano H, Inoue K, Ichinose T, Yanagisawa R, Tomura S, Cho AK, Froines JR, Kumagai Y. Effects of a single intratracheal administration of phenanthraquinone on murine lung. Journal of Applied Toxicology 2005;25(1):47-51.	R827352 (2004) R827352 (Final) R827352C001 (Final)	Abstract from PubMed
Journal Article	Houston D, Wu J, Ong P, Winer A. Structural disparities of urban traffic in Southern California: implications for vehicle-related air pollution exposure in minority and high-poverty neighborhoods. Journal of Urban Affairs 2004;26(5):565-592.	R827352 (2004) R827352 (Final) R827352C015 (Final)	Abstract: Blackwell-Synergy Abstract
Journal Article	Houston D, Ong P, Wu J, Winer A. Proximity of licensed child care facilities to near-roadway vehicle pollution. American Journal of Public Health 2006;96(9):1611-1617.	R827352 (Final) R827352C015 (Final)	Abstract from PubMed Full-text: AJPH Full Text Other: AJPH PDF
Journal Article	Jaques PA, Ambs JL, Grant WL, Sioutas C. Field evaluation of the differential TEOM monitor for continuous PM2.5 mass concentrations. Aerosol Science and Technology 2004;38(Suppl 1):49-59.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Khlystov A, Zhang Q, Jimenez JL, Stanier C, Pandis SN, Canagaratna MR, Fine P, Misra C, Sioutas C. In-situ concentration of semi-volatile aerosol using water-condensation technology. Journal of Aerosol Science 2005;36(7):866-880.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Kikuno S, Taguchi K, Iwamoto N, Yamano S, Cho AK, Froines JR, Kumagai Y. 1,2-Napthoquinone activates vanilloid receptor 1 through increased protein tyrosine phosphorylation, leading to contraction of guinea pig trachea. Toxicology and Applied Pharmacology 2006;210(1-2):47-54.	R827352 (Final) R827352C001 (Final)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Kim HT, Zhu Y, Hinds WC, Lee KW. Experimental study of small cyclones as particle concentrators. Journal of Aerosol Science 2002;33(5):721-733.	R827352 (Final) R827352C006 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Kim S, Chang M-C, Kim D, Sioutas C. A new generation of portable coarse, fine, and ultrafine particle concentrators for use in inhalation toxicology. Inhalation Toxicology 2000;12(1-2):121-137.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: Informa World Abstract
Journal Article	Kim S, Sioutas C, Chang M-C, Gong Jr H. Factors affecting the stability of the performance of ambient fine-particle concentrators. Inhalation Toxicology 2000;12(11, Suppl 4):281-298.	R827352 (2004) R827352 (Final) R827352C012 (Final) R827352C014 (Final) R825513C024 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final) R828598C700 (Final) R829095C004 (2005)	Abstract from PubMed
Journal Article	Kim S, Jaques PA, Chang M, Froines JR, Sioutas C. Versatile aerosol concentration enrichment system (VACES) for simultaneous in vivo and in vitro evaluation of toxic effects of ultrafine, fine and coarse ambient particles. Part I: Development and laboratory characterization. Journal of Aerosol Science 2001;32(11):1281-1297.	R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Kim S, Jaques PA, Chang M, Barone T, Xiong C, Friedlander SK, Sioutas C. Versatile aerosol concentration enrichment system (VACES) for simultaneous in vivo and in vitro evaluation of toxic effects of ultrafine, fine and coarse ambient particles. Part II: Field evaluation. Journal of Aerosol Science 2001;32(11):1299-1314.	R827352 (2004) R827352 (Final) R827352C003 (Final) R827352C014 (Final) R826232 (2000)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Kim S, Shen S, Sioutas C, Zhu Y, Hinds WC. Size distribution and diurnal and seasonal trends of ultrafine particles in source and receptor sites of the Los Angeles Basin. Journal of the Air & Waste Management Association 2002;52(3):297-307.	R827352 (2004) R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Abstract from PubMed Other: University of Southern California PDF
Journal Article	Kleinman MT, Hamade A, Meacher D, Oldham M, Sioutas C, Chakrabarti B, Stram D, Froines JR, Cho AK. Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice. Journal of the Air & Waste Management Association 2005;55(9):1277-1288.	R827352 (2004) R827352 (Final) R827352C001 (Final) R827352C005 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Kleinman MT, Sioutas C, Froines JR, Fanning E, Hamade A, Mendez L, Meacher D, Oldham M. Inhalation of concentrated ambient particulate matter near a heavily trafficked road stimulates antigen-induced airway responses in mice. Inhalation Toxicology 2007;19(Suppl 1):117-126.	R827352 (Final) R832413 (2008) R832413C001 (2007) R832413C001 (2008) R832413C003 (2007)	Abstract from PubMed
Journal Article	Kuhn T, Biswas S, Fine PM, Geller M, Sioutas C. Physical and chemical characteristics and volatility of PM in the proximity of a light-duty vehicle freeway. Aerosol Science and Technology 2005;39(4):347-357.	R827352 (Final) R827352C014 (Final)	Full-text: Informa World Full Text Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Kuhn T, Krudysz M, Zhu Y, Fine PM, Hinds WC, Froines J, Sioutas C. Volatility of indoor and outdoor ultrafine particulate matter near a freeway. Journal of Aerosol Science 2005;36(3):291-302.	R827352 (2004) R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Lee JH, Hopke PK, Holsen TM, Lee D-W, Jaques PA, Sioutas C, Ambs JL. Performance evaluation of continuous PM2.5 mass concentration monitors. Journal of Aerosol Science 2005;36(1):95-109.	R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Li N, Venkatesan MI, Miguel A, Kaplan R, Gujuluva C, Alam J, Nel A. Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. Journal of Immunology 2000;165(6):3393-3401.	R827352 (2004) R827352 (Final) R827352C002 (Final) R827352C013 (Final)	Abstract from PubMed Full-text: Journal of Immunology Full Text Other: Journal of Immunology PDF
Journal Article	Li N, Kim S, Wang M, Froines J, Sioutas C, Nel A. Use of a stratified oxidative stress model to study the biological effects of ambient concentrated and diesel exhaust particulate matter. Inhalation Toxicology 2002;14(5):459-486.	R827352 (2004) R827352 (Final) R827352C002 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Li N, Hao M, Phalen RF, Hinds WC, Nel AE. Particulate air pollutants and asthma: a paradigm for the role of oxidative stress in PM-induced adverse health effects. Clinical Immunology 2003;109(3):250-265.	R827352 (2004) R827352 (Final) R827352C002 (Final) R827352C006 (Final) R827352C016 (Final)	Abstract from PubMed
Journal Article	Li N, Sioutas S, Cho A, Schmitz D, Misra C, Sempf J, Wang M, Oberly T, Froines J, Nel A. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environmental Health Perspectives 2003;111(4):455-460.	R827352 (2004) R827352 (Final) R827352C001 (Final) R827352C002 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Li N, Alam J, Venkatesan I, Eiguren-Fernandez A, Schmitz D, Di Stefano E, Slaughter N, Killeen E, Wang X, Huang A, Wang M, Miguel AH, Cho A, Sioutas C, Nel AE. Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. Journal of Immunology 2004;173(5):3467-3481.	R827352 (2004) R827352 (Final) R827352C001 (Final) R827352C002 (Final) R827352C013 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Journal of Immunology Full Text Other: Journal of Immunology PDF
Journal Article	Li N, Nel AE. Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: implications for the impact of particulate pollutants on asthma. Antioxidants & Redox Signaling 2006;8(1-2):88-98.	R827352 (Final) R827352C002 (Final)	Abstract from PubMed
Journal Article	Linn WS, Szlachcic Y, Gong Jr H, Kinney PL, Berhane KT. Air pollution and daily hospital admissions in metropolitan Los Angeles. Environmental Health Perspectives 2000;108(5):427-434.	R827352 (2004) R827352 (Final) R827352C012 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final) R826708C001 (2000)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Linn WS, Avila M, Gong H Jr. Exhaled nitric oxide: sources of error in offline measurement. Archives of Environmental Health 2004;59(8):385-391.	R827352 (Final) R827352C011 (Final) R827352C012 (Final) R831861 (2005)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Lippmann M, Frampton M, Schwartz J, Dockery D, Schlesinger R, Koutrakis P, Froines J, Nel A, Finkelstein J, Godleski J, Kaufman J, Koenig J, Larson T, Luchtel D, Liu L-J S, Oberdorster G, Peters A, Sarnat J, Sioutas C, Suh H, Sullivan J, Utell M, Wichmann E, Zelikoff J. The U.S. Environmental Protection Agency Particulate Matter Health Effects Research Centers Program: a midcourse report of status, progress, and plans. Environmental Health Perspectives 2003;111(8):1074-1092.	R827352 (Final) R827352C002 (Final) R827352C014 (Final) R827351 (2002) R827351 (Final) R827353 (Final) R827353C006 (Final) R827353C015 (Final) R827354 (Final) R827355 (Final)	Abstract from PubMed Associated PubMed link Full-text: Environmental Health Perspectives Full Text
Journal Article	Lu R, Wu J, Turco RP, Winer AM, Atkinson R, Arey J, Paulson SE, Lurmann FW, Miguel AH, Eiguren-Fernandez A. Naphthalene distributions and human exposure in Southern California. Atmospheric Environment 2005;39:489-507.	R827352 (2004) R827352 (Final) R827352C013 (Final) R827352C015 (Final) R831861 (2004) R831861 (2005)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Majestic BJ, Schauer JJ, Shafer MM, Turner JR, Fine PM, Singh M, Sioutas C. Development of a wet-chemical method for the speciation of iron in atmospheric aerosols. Environmental Science & Technology 2006;40(7):2346-2351.	R827352 (Final)	Abstract from PubMed
Journal Article	McConnell R, Jones C, Milam J, Gonzalez P, Berhane K, Clement L, Richardson J, Hanley-Lopez J, Kwong K, Maalouf N, Galvan J, Platts-Mills T. Cockroach counts and house dust allergen concentrations after professional cockroach control and cleaning. Annals of Allergy, Asthma & Immunology 2003;91(6):546-552.	R827352 (2004) R827352 (Final) R827352C007 (Final) R831861 (2004) R831861 (2005)	Abstract from PubMed
Journal Article	McConnell R, Berhane K, Gilliland FD, Molitor J, Thomas D, Lurmann F, Avol E, Gauderman WJ, Peters JM. Prospective study of air pollution and bronchitic symptoms in children with asthma. American Journal of Respiratory and Critical Care Medicine 2003;168(7):790-797.	R827352 (2004) R827352 (Final) R827352C007 (Final) R827352C009 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final) R826708C003 (Final) R831861 (2004) R831861 (2005)	Abstract from PubMed Full-text: American Thoracic Society Full Text Other: American Thoracic Society PDF
Journal Article	McConnell R, Berhane K, Molitor J, Gilliland F, Künzli N, Thorne P, Thomas D, Gauderman J, Avol E, Lurmann F, Rappaport E, Jerrett M, Peters JM. Dog ownership enhances symptomatic responses to air pollution in children with asthma. Environmental Health Perspectives 2006;114(12):1910-1915.	R827352 (Final) R827352C007 (Final) R831861 (2005)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	McConnell R, Berhane K, Yao L, Lurmann FW, Avol E, Peters JM. Predicting residential ozone deficits from nearby traffic. Science of the Total Environment 2006;363(1-3):166-174.	R827352 (Final) R827352C007 (Final) R831861 (2004) R831861 (2005) R831861C001 (2005)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	McConnell R, Berhane K, Yao L, Jerrett M, Lurmann F, Gilliland F, Kunzli N, Gauderman J, Avol E, Thomas D, Peters J. Traffic, susceptibility, and childhood asthma. Environmental Health Perspectives 2006;114(5):766-772.	R827352 (Final) R827352C007 (Final) R831861 (2004) R831861 (2005)	Full-text from PubMed Abstract from PubMed Associated PubMed link
Journal Article	Miguel AH, Eiguren-Fernandez A, Jaques PA, Froines JR, Grant BL, Mayo PR, Sioutas C. Seasonal variation of the particle size distribution of polycyclic aromatic hydrocarbons and of major aerosol species in Claremont, California. Atmospheric Environment 2004;38(20):3241-3251.	R827352 (2004) R827352 (Final) R827352C013 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Miguel A, Eiguren-Fernandez A, Sioutas C, Fine P, Geller M, Mayo P. Observations of twelve USEPA priority polycyclic aromatic hydrocarbons in the Aitken size range (10-32 nm Dp). Aerosol Science and Technology 2005;39(5):415-418.	R827352 (Final) R827352C013 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Misra C, Geller MD, Shah P, Sioutas C, Solomon PA. Development and evaluation of a continuous coarse (PM10 - PM2.5) particle monitor. Journal of the Air & Waste Management Association 2001;51(9):1309-1317.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract from PubMed Other: University of Southern California PDF
Journal Article	Misra C, Kim S, Shen S, Sioutas C. A high flow rate, very low pressure drop impactor for inertial separation of ultrafine from accumulation mode particles. Journal of Aerosol Science 2002;33(5):735-752.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Misra C, Singh M, Shen S, Sioutas C, Hall PM. Development and evaluation of a personal cascade impactor sampler (PCIS). Journal of Aerosol Science 2002;33(7):1027-1047.	R827352 (2004) R827352 (Final) R827352C014 (Final) R828678C007 (2001) R828678C007 (2002) R828678C007 (2003) R828678C007 (2004) R828678C007 (Final) R828678C009 (2003) R828678C009 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Misra C, Geller M, Sioutas C, Solomon P. Development and evaluation of a PM10 impactor-inlet for a continuous coarse particle monitor. Aerosol Science and Technology 2003;37(3):271-281.	R827352 (Final) R827352C014 (Final)	Full-text: Informa World Full Text Abstract: Informa World Abstract
Journal Article	Misra C, Fine PM, Singh M, Sioutas C. Development and evaluation of a compact facility for exposing humans to concentrated ambient ultrafine particles. Aerosol Science and Technology 2004;38(1):27-35.	R827352 (2004) R827352 (Final) R827352C014 (Final) R828678C009 (2001) R828678C009 (Final)	Full-text: Informa World Full Text Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Nel AE, Diaz-Sanchez D, Li N. The role of particulate pollutants in pulmonary inflammation and asthma: evidence for the involvement of organic chemicals and oxidative stress. Current Opinion in Pulmonary Medicine 2001;7(1):20-26.	R827352 (2004) R827352 (Final) R827352C002 (Final)	Abstract from PubMed
Journal Article	Nel AE. Air pollution-related illness: effects of particles. Science 2005;308(5723):804-806.	R827352 (Final) R827352C002 (Final)	Abstract: AAAS Abstract
Journal Article	Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science 2006;311(5761):622-627.	R827352 (Final)	Abstract from PubMed Full-text: Science Full Text
Journal Article	Oldham MJ, Phalen RF. Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties. The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology 2002;268(1):59-65.	R827352 (2004) R827352 (Final) R827352C016 (Final)	Abstract from PubMed
Journal Article	Oldham MJ, Phalen RF, Robinson RJ, Kleinman MT. Performance of a portable whole-body mouse exposure system. Inhalation Toxicology 2004;16(9):657-662.	R827352 (2004) R827352 (Final) R827352C005 (Final) R827352C016 (Final)	Abstract from PubMed
Journal Article	Pan C-JG, Schmitz DA, Cho AK, Froines J, Fukuto JM. Inherent redox properties of diesel exhaust particles: catalysis of the generation of reactive oxygen species by biological reductants. Toxicological Sciences 2004;81(1):225-232.	R827352 (2004) R827352 (Final) R827352C001 (Final)	Full-text: Oxford Journals Full Text Abstract: Oxford Journals Abstract Other: Oxford Journals PDF
Journal Article	Phalen RF, Oldham MJ. Methods for modeling particle deposition as a function of age. Respiratory Physiology 2001;128(1):119-130.	R827352 (2004) R827352 (Final) R827352C016 (Final)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Phalen RF, Oldham MJ, Nel AE. Tracheobronchial particle dose considerations for in vitro toxicology studies. Toxicological Sciences 2006;92(1):126-132.	R827352 (Final) R827352C016 (Final)	Abstract from PubMed Full-text: Oxford Journals Full Text Other: Oxford Journals PDF
Journal Article	Phalen R. The particulate air pollution controversy. Nonlinearity in Biology, Toxicology, and Medicine 2004;2(1):259-292.	R827352 (2004) R827352 (Final) R827352C016 (Final)	Abstract: Ingenta Connect Abstract
Journal Article	Phousongphouang PT, Arey J. Sources of the atmospheric contaminants, 2-nitrobenzanthrone and 3-nitrobenzanthrone. Atmospheric Environment 2003;37(23):3189-3199.	R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Phuleria HC, Fine PM, Zhu Y, Sioutas C. Air quality impacts of the October 2003 Southern California wildfires. Journal of Geophysical Research–Atmospheres 2005;110(D7):D07S20, doi:10.1029/2004JD004626.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: AGU Abstract Other: UCLA PDF
Journal Article	Phuleria HC, Geller MD, Fine PM, Sioutas C. Size-resolved emissions of organic tracers from light- and heavy-duty vehicles measured in a California roadway tunnel. Environmental Science & Technology 2006;40(13):4109-4118.	R827352 (Final)	Abstract from PubMed
Journal Article	Prophete C, Maciejczyk P, Salnikow K, Gould T, Larson T, Koenig J, Jaques P, Sioutas C, Lippmann M, Cohen M. Effects of select PM-associated metals on alveolar macrophage phosphorylated ERK1 and -2 and iNOS expression during ongoing alteration in iron homeostasis. Journal of Toxicology and Environmental Health, Part A 2006;69(10):935-951.	R827352 (Final) R827352C014 (Final) R827351 (Final) R827351C008 (Final) R827351C010 (Final) R827355 (Final) R827355C008 (Final)	Abstract from PubMed Other: InformaWorld Abstract
Journal Article	Reisen F, Wheeler S, Arey J. Methyl-and dimethyl-/ethyl-nitronaphthalenes measured in ambient air in Southern California. Atmospheric Environment 2003;37(26):3653-3657.	R827352 (2004) R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Reisen F, Arey J. Atmospheric reactions influence seasonal PAH and nitro-PAH concentrations in the Los Angeles Basin. Environmental Science & Technology 2005;39(1):64-73.	R827352 (Final)	Abstract from PubMed
Journal Article	Rodriguez CE, Shinyashiki M, Froines J, Yu RC, Fukuto JM, Cho AK. An examination of quinone toxicity using the yeast Saccharomyces cerevisiae model system. Toxicology 2004;201(1-3):185-196.	R827352 (2004) R827352 (Final) R827352C001 (Final)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Rodriguez CE, Fukuto JM, Taguchi K, Froines J, Cho AK. The interactions of 9,10-phenanthrenequinone with glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a potential site for toxic actions. Chemico-Biological Interactions 2005;155(1-2):97-110.	R827352 (Final) R827352C001 (Final)	Abstract from PubMed Full-text: Science Direct Full Text Other: Science Direct PDF
Journal Article	Sardar SB, Fine PM, Yoon H, Sioutas C. Associations between particle number and gaseous co-pollutant concentrations in the Los Angeles Basin. Journal of the Air & Waste Management Association 2004;54(8):992-1005.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Sardar SB, Fine PM, Mayo PR, Sioutas C. Size-fractionated measurements of ambient ultrafine particle chemical composition in Los Angeles using the NanoMOUDI. Environmental Science & Technology 2005;39(4):932-944.	R827352 (Final) R827352C014 (Final)	Full-text: ACS Full Text Abstract: ACS Abstract Other: ACS PDF
Journal Article	Sardar SB, Fine PM, Sioutas C. Seasonal and spatial variability of the size-resolved chemical composition of particulate matter (PM10) in the Los Angeles Basin. Journal of Geophysical Research–Atmospheres 2005;110(D7):D07S08,doi:10.1029/2004JD004627	R827352 (2004) R827352 (Final) R827352C014 (Final)	Abstract: AGU Abstract
Journal Article	Sardar SB, Geller MD, Sioutas C, Solomon PA. Development and evaluation of a high-volume dichotomous sampler for chemical speciation of coarse and fine particles. Journal of Aerosol Science 2006;37(11):1455-1466.	R827352 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Shen S, Jaques PA, Zhu Y, Geller MD, Sioutas C. Evaluation of the SMPS–APS system as a continuous monitor for measuring PM2.5, PM10 and course (PM2.5–10) concentrations. Atmospheric Environment 2002;36(24):3939-3950.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Singh M, Jaques PA, Sioutas C. Size distribution and diurnal characteristics of particle-bound metals in source and receptor sites of the Los Angeles Basin. Atmospheric Environment 2002;36(10):1675-1689.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Singh M, Misra C, Sioutas C. Field evaluation of a personal cascade impactor sampler (PCIS). Atmospheric Environment 2003;37(34):4781-4793.	R827352 (Final) R827352C014 (Final) R828678C009 (2002) R828678C009 (2003) R828678C009 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Sioutas C, Kim S, Chang M, Terrell LL, Gong Jr H. Field evaluation of a modified DataRAM MIE scattering monitor for real-time PM2.5 mass concentration measurements. Atmospheric Environment 2000;34(28):4829-4838.	R827352 (Final) R827352C012 (Final) R827352C014 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Sioutas C, Pandis SN, Allen DT, Solomon PA. Special issue of Atmospheric Environment on findings from EPA’s Particulate Matter Supersites Program. Atmospheric Environment 2004;38(20):3101-3106.	R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Sioutas C, Delfino RJ, Singh M. Exposure assessment for atmospheric ultrafine particles (UFPs) and implications in epidemiologic research. Environmental Health Perspectives 2005;113(8):947-955.	R827352 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Stolzenburg MR, Dutcher DD, Kirby BW, Hering SV. Automated measurement of the size distribution of airborne particulate nitrate. Aerosol Science and Technology 2003;37(7):537-546.	R827352 (2004) R827352 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Taguchi K, Fujii S, Yamano S, Cho AK, Kamisuki S, Nakai Y, Sugawara F, Froines JR, Kumagai Y. An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress. Free Radical Biology & Medicine 2007;43(5):789-799.	R827352 (Final)	Abstract from PubMed Abstract: Science Direct Abstract
Journal Article	Venkataraman C, Habib G, Eiguren-Fernandez A, Miguel AH, Friedlander SK. Residential biofuels in South Asia: carbonaceous aerosol emissions and climate impacts. Science 2005;307(5714):1454-1456.	R827352 (Final) R827352C013 (Final)	Abstract from PubMed Other: RSC PDF
Journal Article	Westerdahl D, Fruin S, Sax T, Fine PM, Sioutas C. Mobile platform measurements of ultrafine particles and associated pollutant concentrations on freeways and residential streets in Los Angeles. Atmospheric Environment 2005;39(20):3597-3610.	R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Whitekus MJ, Li N, Zhang M, Wang M, Horwitz MA, Nelson SK, Horwitz LD, Brechun N, Diaz-Sanchez D, Nel AE. Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization. The Journal of Immunology 2002;168(5):2560-2567.	R827352 (Final) R827352C002 (Final) R826708 (2000) R826708 (2001) R826708 (2002) R826708 (Final) R826708C001 (Final) R826708C002 (Final) R831861 (2004) R831861 (2005)	Abstract from PubMed Full-text: Journal of Immunology Full Text Other: Journal of Immunology PDF
Journal Article	Wilhelm M, Ritz B. Residential proximity to traffic and adverse birth outcomes in Los Angeles County, California, 1994–1996. Environmental Health Perspectives 2003;111(2):207-216.	R827352 (Final) R827352C008 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Wilhelm M, Ritz B. Local variations in CO and particulate air pollution and adverse birth outcomes in Los Angeles County, California, USA. Environmental Health Perspectives 2005;113(9):1212-1221.	R827352 (Final) R827352C008 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Wold LE, Simkhovich BZ, Kleinman MT, Nordlie MA, Dow JS, Sioutas C, Kloner RA. In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias. Cardiovascular Toxicology 2006;6(1):69-78.	R827352 (Final) R832413 (2008) R832413C001 (2007)	Abstract from PubMed
Journal Article	Wu J, Lurmann F, Winer A, Lu R, Turco R, Funk TH. Development of an individual exposure model for application to the Southern California Children’s Health Study. Atmospheric Environment 2005;39(2):259-273.	R827352 (Final) R827352C015 (Final) R828172 (Final) R831845 (2005) R831861 (2004) R831861 (2005)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Wu J, Funk T, Lurmann F, Winer A. Improving spatial accuracy of roadway networks and geocoded addresses. Transactions in GIS 2005;9(4):585-601.	R827352 (Final) R827352C015 (Final) R831845 (2005) R831861 (2005)	Abstract: Blackwell-Synergy Abstract
Journal Article	Xia T, Korge P, Weiss JN, Li N, Venkatesan MI, Sioutas C, Nel A. Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity. Environmental Health Perspectives 2004;112(14):1347-1358.	R827352 (Final) R827352C002 (Final) R827352C014 (Final)	Abstract from PubMed Full-text: Environmental Health Perspectives Full Text Other: Environmental Health Perspectives PDF
Journal Article	Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, Sioutas C, Yeh JI, Wiesner MR, Nel AE. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Letters 2006;6(8):1794-1807.	R827352 (Final) R827352C002 (Final) R827352C014 (Final) R832413 (2008) R832413C001 (2007) R832413C001 (2008) R832413C002 (2006) R832413C002 (2008)	Abstract from PubMed
Journal Article	Yu RC, Teh HW, Jaques PA, Sioutas C, Froines JR. Quality control of semi-continuous mobility size-fractionated particle number concentration data. Atmospheric Environment 2004;38(20):3341-3348.	R827352 (2004) R827352 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhang KM, Wexler AS, Zhu YF, Hinds WC, Sioutas C. Evolution of particle number distribution near roadways. Part II: The ‘Road-to-Ambient’ process. Atmospheric Environment 2004;38(38):6655-6665.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhang KM, Wexler AS, Niemeier DA, Zhu YF, Hinds WC, Sioutas C. Evolution of particle number distribution near roadways. Part III: Traffic analysis and on-road size resolved particulate emission factors. Atmospheric Environment 2005;39(22):4155-4166.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhao Y, Bein KJ, Wexler AS, Misra C, Fine PM, Sioutas C. Field evaluation of the versatile aerosol concentration enrichment system (VACES) particle concentrator coupled to the rapid single-particle mass spectrometer (RSMS-3). Journal of Geophysical Research–Atmospheres 2005;110(D7):D07S02, doi:10.1029/2004JD004644.	R827352 (Final) R827352C014 (Final)	Abstract: AGU Abstract Other: Journal of Geophysical Research–Atmospheres PDF
Journal Article	Zhu Y, Hinds WC, Kim S, Sioutas C. Concentration and size distribution of ultrafine particles near a major highway. Journal of the Air & Waste Management Association 2002;52(9):1032-1042.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Abstract from PubMed
Journal Article	Zhu Y, Hinds WC, Kim S, Shen S, Sioutas C. Study of ultrafine particles near a major highway with heavy-duty diesel traffic. Atmospheric Environment 2002;36(27):4323-4335.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhu Y, Hinds WC, Shen S, Sioutas C. Seasonal trends of concentration and size distribution of ultrafine particles near major highways in Los Angeles. Aerosol Science and Technology 2004;38(Suppl 1):5-13.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Abstract: Informa World Abstract Other: Informa World PDF
Journal Article	Zhu Y, Hinds WC, Krudysz M, Kuhn T, Froines J, Sioutas C. Penetration of freeway ultrafine particles into indoor environments. Journal of Aerosol Science 2005;36(3):303-322.	R827352 (Final) R827352C006 (Final) R827352C014 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhu Y, Hinds WC. Predicting particle number concentrations near a highway based on vertical concentration profile. Atmospheric Environment 2005;39(8):1557-1566.	R827352 (Final) R827352C006 (Final)	Full-text: Science Direct Full Text Abstract: Science Direct Abstract Other: Science Direct PDF
Journal Article	Zhu Y, Kuhn T, Mayo P, Hinds WC. Comparison of daytime and nighttime concentration profiles and size distributions of ultrafine particles near a major highway. Environmental Science & Technology 2006;40(8):2531-2536.	R827352 (Final) R827352C006 (Final)	Abstract from PubMed
Journal Article	Zhu Y, Yu N, Kuhn T, Hinds WC. Field comparison of P-Trak and condensation particle counters. Aerosol Science and Technology 2006;40(6):422-430.	R827352 (Final) R827352C006 (Final)	Abstract: Ingenta Connect Abstract Other: Taylor & Francis PDF
Journal Article	Zhu Y, Eiguren-Fernandez A, Hinds WC, Miguel AH. In-cabin commuter exposure to ultrafine particles on Los Angeles freeways. Environmental Science & Technology 2007;41(7):2138-2145.	R827352 (Final) R832413 (2008) R832413C005 (2007) R832413C005 (2008)	Abstract from PubMed

Supplemental Keywords:

aldehydes, carbonyls, quinones, MOUDI, polycyclic aromatic hydrocarbons (PAHs), particle size distribution, oxidative stress, oxygen radicals, antioxidant responses, inflammation, cytotoxicity, asthma, airborne particulate matter, particle concentrator, mechanism, allergens, bioaerosols, dosimetry, ultrafine, fine and coarse particles, REHEX, clinical human exposures, source-receptor, measurement error, geo-code, source/receptor analysis, photochemistry, trajectory modeling, peroxides, , Air, Geographic Area, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, indoor air, Risk Assessments, genetic susceptability, Health Risk Assessment, Children's Health, particulate matter, Environmental Chemistry, State, aerosols, exposure assessment, California (CA), environmentally caused disease, environmental hazard exposures, acute exposure, allergen, health effects, indoor air quality, allergens, outdoor air, particle concentrator, air quality, lead, assessment of exposure, childhood respiratory disease, human health risk, toxics, air toxics, human health effects, particulates, sensitive populations, toxicology, biological response, environmental triggers, air pollution, airway disease, atmospheric chemistry, children, bioaerosols, trajectory modeling, dosimetry, household, inhaled particles, PAH, environmental health hazard, asthma triggers, allergic response, ambient aerosol, asthma, human exposure, Human Health Risk Assessment, PM, particle transport
Relevant Websites:

Full Final Technical Report (PDF, 112pp., 1.04MB, about PDF)
http://www.scpcs.ucla.edu

Progress and Final Reports:
2003 Progress Report
2004 Progress Report
Original Abstract

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827352C001 The Chemical Toxicology of Particulate Matter
R827352C002 Pro-inflammatory and the Pro-oxidative Effects of Diesel Exhaust Particulate in Vivo and in Vitro
R827352C003 Measurement of the “Effective” Surface Area of Ultrafine and Accumulation Mode PM (Pilot Project)
R827352C004 Effect of Exposure to Freeways with Heavy Diesel Traffic and Gasoline Traffic on Asthma Mouse Model
R827352C005 Effects of Exposure to Fine and Ultrafine Concentrated Ambient Particles near a Heavily Trafficked Freeway in Geriatric Rats (Pilot Project)
R827352C006 Relationship Between Ultrafine Particle Size Distribution and Distance From Highways
R827352C007 Exposure to Vehicular Pollutants and Respiratory Health
R827352C008 Traffic Density and Human Reproductive Health
R827352C009 The Role of Quinones, Aldehydes, Polycyclic Aromatic Hydrocarbons, and other Atmospheric Transformation Products on Chronic Health Effects in Children
R827352C010 Novel Method for Measurement of Acrolein in Aerosols
R827352C011 Off-Line Sampling of Exhaled Nitric Oxide in Respiratory Health Surveys
R827352C012 Controlled Human Exposure Studies with Concentrated PM
R827352C013 Particle Size Distributions of Polycyclic Aromatic Hydrocarbons in the LAB
R827352C014 Physical and Chemical Characteristics of PM in the LAB (Source Receptor Study)
R827352C015 Exposure Assessment and Airshed Modeling Applications in Support of SCPC and CHS Projects
R827352C016 Particle Dosimetry
R827352C017 Conduct Research and Monitoring That Contributes to a Better Understanding of the Measurement, Sources, Size Distribution, Chemical Composition, Physical State, Spatial and Temporal Variability, and Health Effects of Suspended PM in the Los Angeles Basin (LAB)

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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