Grantee Research Project Results

Final Report: The Chemical Toxicology of Particulate Matter

EPA Grant Number: R827352C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R827352
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Southern California Particle Center
Center Director: Froines, John R.
Title: The Chemical Toxicology of Particulate Matter
Investigators: Cho, Arthur K. , Froines, John R.
Institution: University of California - Los Angeles
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2005 (Extended to May 31, 2006)
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text | Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

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

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/Accomplishments (Outputs/Outcomes):

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 Los Angeles Basin (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.
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. Ultrafine particles (UF), in general, had greater potency in terms of redox activity per mass, while the greater mass concentration of fine particles (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.
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
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.
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.

References:

Cho A, Di Stefano E, Ying Y, Rodriguez CE, Schmitz DA, Miguel AH, Eiguren-Fernandez A, Kobayashi TE, Avol E, Froines JR. Determination of four quinones in diesel exhaust particles, SRM 1649a and atmospheric PM2.5. Aerosol Science and Technology 2004;38:68-81.

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;99:40-47.

Li N, Sioutas C, Cho A, Schmitz D, Misra C, Sempf J, Wang M, Oberley T, Froines JR, Nel A. Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environmental Health Perspectives 2003;111:455-460.

Technical Report:

Full Final Technical Report (PDF, 11pp., 51.3KB, about PDF)

Journal Articles on this Report : 10 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 10 publications	10 publications in selected types	All 10 journal articles
Other center views:	All 150 publications	149 publications in selected types	All 149 journal articles

Publications
Type	Citation	Sub Project	Document Sources
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)	Full-text: Taylor & Francis-Full Text PDF Exit Abstract: Taylor & Francis-Abstract Exit
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) R832413C003 (2010) R832413C003 (Final)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
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) R832413C003 (2010)	Abstract from PubMed Abstract: Wiley-Abstract Exit
Journal Article	Kikuno S, Taguchi K, Iwamoto N, Yamano S, Cho AK, Froines JR, Kumagai Y. 1,2-Naphthoquinone 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) R832413C003 (2010)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
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) R832413C003 (2010)	Abstract from PubMed Full-text: Taylor & Francis-Full Text PDF Exit Abstract: Taylor & Francis-Abstract Exit
Journal Article	Li N, Sioutas C, Cho A, Schmitz D, Misra C, Sempf J, Wang M, Oberley 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)	Full-text from PubMed Abstract from PubMed Associated PubMed link Full-text: ResearchGate - Abstract & Full Text PDF Exit
Journal Article	Li N, Alam J, Venkatesan MI, 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 PDF Exit Abstract: Journal of Immunology-Abstract and Full Text HTML Exit
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)	Abstract from PubMed Full-text: ToxSci-Full Text HTML Exit Abstract: ToxSci-Abstract Exit Other: ToxSci-Full Text PDF Exit
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: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit
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) R832413C003 (2010)	Abstract from PubMed Full-text: ScienceDirect-Full Text HTML Exit Abstract: ScienceDirect-Abstract Exit Other: ScienceDirect-Full Text PDF Exit

Supplemental Keywords:

RFA, Health, Scientific Discipline, Air, HUMAN HEALTH, particulate matter, Environmental Chemistry, Air Pollutants, Risk Assessments, Biochemistry, Health Effects, Biology, particulates, ambient aerosol, asthma, toxicology, quinones, human health effects, airway disease, allergic airway disease, air pollution, PAH, particulate exposure, human exposure, toxicity, breath samples, allergens, particle concentrator, airborne urban contaminants, human health risk, genetic susceptibility, aerosols, atmospheric chemistry, dosimetry

Relevant Websites:

Full Final Technical Report (PDF, 11pp., 51.3KB, about PDF)
http://www.scpcs.ucla.edu Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R827352 Southern California Particle Center

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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