Oxidative stress is a potential mechanism of action for particulate matter (PM) toxicity and can occur when the body’s antioxidant capacity cannot counteract or detoxify harmful effects of reactive oxygen species (ROS) due to an excess presence of ROS. ROS are introduced to the body via inhalation of PM with these species present on and/or within the particles (particle-bound ROS) and/or through catalytic generation of ROS in vivo after inhaling redox-active PM species (oxidative potential, OP). The recent development of acellular OP measurement techniques has led to a surge in research across the globe. In this review, particle-bound ROS techniques are discussed briefly while OP measurements are the focus due to an increasing number of epidemiologic studies using OP measurements showing associations with adverse health effects in some studies. The most common OP measurement techniques, including the dithiothreitol assay, glutathione assay, and ascorbic acid assay, are discussed along with evidence for utility of OP measurements in epidemiologic studies and PM characteristics that drive different responses between assay types (such as species composition, emission source, and photochemistry). Overall, most OP assays respond to metals like copper than can be found in emission sources like vehicles. Some OP assays respond to organics, especially photochemically aged organics, from sources like biomass burning. Select OP measurements have significant associations with certain cardiorespiratory end points, such as asthma, congestive heart disease, and lung cancer. In fact, multiple studies have found that exposure to OP measured using the dithiothreitol and glutathione assays drives higher risk ratios for certain cardiorespiratory outcomes than PM mass, suggesting OP measurements may be integrating the health-relevant fraction of PM and will be useful tools for future health analyses. The compositional impacts, including species and emission sources, on OP could have serious implications for health-relevant PM exposure. Though more work is needed, OP assays show promise for health studies as they integrate the impacts of PM species and properties on catalytic redox reactions into one measurement, and current work highlights the importance of metals, organic carbon, vehicles, and biomass burning emissions to PM exposures that could impact health.

Abstract. The ability of certain components of particulate matter to induce oxidative stress through the generation of reactive oxygen species (ROS) in vivo may be one mechanism accounting for observed linkages between ambient aerosols and adverse health outcomes. A variety of assays have been used to measure this so-called aerosol oxidative potential. We developed a semi-automated system to quantify oxidative potential of filter aqueous extracts utilizing the dithiothreitol (DTT) assay and report here the development of a similar semi-automated system for the ascorbic acid (AA) assay. Approximately 500 PM2.5 filter samples collected in contrasting locations in the southeastern US were analyzed for a host of aerosol species, along with AA and DTT activities. We present a detailed contrast in findings from these two assays. Water-soluble AA activity was higher in summer and fall than in winter, with highest levels near heavily trafficked highways, whereas DTT activity was higher in winter compared to summer and fall and more spatially homogeneous. AA activity was nearly exclusively correlated with water-soluble Cu (r  =  0.70–0.94 at most sites), whereas DTT activity was correlated with organic and metal species. Source apportionment models, positive matrix factorization (PMF) and a chemical mass balance method with ensemble-averaged source impact profiles (CMB-E), suggest a strong contribution from traffic emissions and secondary processes (e.g., organic aerosol oxidation or metals mobilization by secondary acids) to both AA and DTT activities in urban Atlanta. In contrast, biomass burning was a large source for DTT activity, but insignificant for AA. AA activity was not correlated with PM2.5 mass, while DTT activity co-varied strongly with mass (r  =  0.49–0.86 across sites and seasons). Various linear models were developed to estimate AA and DTT activities for the central Atlanta Jefferson Street site, based on the CMB-E sources. The models were then used to estimate daily oxidative potential at this site over the 1998–2009 period. Time series epidemiological analyses were conducted to assess daily emergency department (ED) visits data for the five-county Atlanta metropolitan area based on the estimated 10-year backcast oxidative potential. Estimated AA activity was not statistically associated with any tested health outcome, while DTT activity was associated with ED visits for both asthma or wheeze and congestive heart failure. The findings point to the importance of both organic components and transition metals from biomass burning and mobile sources to adverse health outcomes in this region.

Exposure to atmospheric fine particulate matter (PM2.5) is associated with cardiorespiratory morbidity and mortality, but the mechanisms are not well understood. We assess the hypothesis that PM2.5 induces oxidative stress in the body via catalytic generation of reactive oxygen species (ROS). A dithiothreitol (DTT) assay was used to measure the ROS-generation potential of water-soluble PM2.5. Source apportionment on ambient (Atlanta, GA) PM2.5 was performed using the chemical mass balance method with ensemble-averaged source impact profiles. Linear regression analysis was used to relate PM2.5 emission sources to ROS-generation potential and to estimate historical levels of DTT activity for use in an epidemiologic analysis for the period of 1998-2009. Light-duty gasoline vehicles (LDGV) exhibited the highest intrinsic DTT activity, followed by biomass burning (BURN) and heavy-duty diesel vehicles (HDDV) (0.11 ± 0.02, 0.069 ± 0.02, and 0.052 ± 0.01 nmol min(-1) μg(-1)source, respectively). BURN contributed the largest fraction to total DTT activity over the study period, followed by LDGV and HDDV (45, 20, and 14%, respectively). DTT activity was more strongly associated with emergency department visits for asthma/wheezing and congestive heart failure than PM2.5. This work provides further epidemiologic evidence of a biologically plausible mechanism, that of oxidative stress, for associations of adverse health outcomes with PM2.5 mass and supports continued assessment of the utility of the DTT activity assay as a measure of ROS-generating potential of particles.

Abstract. We assess the potential of the water-soluble fraction of atmospheric fine aerosols in the southeastern United States to generate reactive oxygen species (ROS) and identify major ROS-associated emission sources. ROS-generation potential of particles was quantified by the dithiothreitol (DTT) assay and involved analysis of fine particulate matter (PM) extracted from high-volume quartz filters (23 h integrated samples) collected at various sites in different environmental settings in the southeast, including three urban-Atlanta sites, in addition to a rural site. Paired sampling was conducted with one fixed site in Atlanta (Jefferson Street), representative of the urban environment, with the others rotating among different sites, for ~250 days between June 2012 and September 2013 (N=483). A simple linear regression between the DTT activity and aerosol chemical components revealed strong associations between PM ROS-generation potential and secondary organic aerosol (WSOC – water-soluble organic carbon) in summer, and biomass burning markers in winter. Redox-active metals were also somewhat correlated with the DTT activity, but mostly at urban and roadside sites. Positive matrix factorization (PMF) was applied to apportion the relative contribution of various sources to the ROS-generation potential of water-soluble PM2.5 in urban Atlanta. PMF showed that vehicular emissions contribute uniformly throughout the year (12–25%), while secondary oxidation processes dominated the DTT activity in summer (46%) and biomass burning in winter (47%). Road dust was significant only during drier periods (~12% in summer and fall). Source apportionment by chemical mass balance (CMB) was reasonably consistent with PMF, but with higher contribution from vehicular emissions (32%). Given the spatially large data set of PM sampled over an extended period, the study reconciles the results from previous work that showed only region- or season-specific aerosol components or sources contributing to PM ROS activity, possibly due to smaller sample sizes. The ubiquitous nature of the major sources of PM-associated ROS suggests widespread population exposures to aerosol components that have the ability to catalyze the production of oxidants in vivo.

Abstract. We assess the potential of the water-soluble fraction of atmospheric fine aerosols in the southeastern US to generate reactive oxygen species (ROS) and identify major ROS-associated emission sources. ROS-generation potential of particles was quantified by the dithiothreitol (DTT) assay and involved analysis of fine particulate matter (PM) extracted from high-volume quartz filters (23 h integrated samples) collected at various sites in different environmental settings in the southeast, including three urban Atlanta sites, in addition to a rural site. Paired sampling was conducted with one fixed site in Atlanta (Jefferson Street), representative of the urban environment, with the others rotating among different sites, for ~250 days between June 2012 and September 2013 (N = 483). A simple linear regression between the DTT activity and aerosol chemical components revealed strong associations between PM ROS generation potential and secondary organic aerosol (WSOC) in summer, and biomass burning markers in winter. Redox-active metals were also correlated with the DTT activity, but mostly at urban and roadside sites. Positive matrix factorization (PMF) was applied to apportion the relative contribution of various sources to the ROS generation potential of water-soluble PM2.5 in urban Atlanta. PMF showed that vehicular emissions contribute uniformly throughout the year (12 to 25%), while secondary oxidation processes dominated the DTT activity in summer (46%) and biomass burning in winter (47%). Mineral dust was significant only during drier periods (~12% in summer and fall). Source apportionment by chemical mass balance (CMB) was reasonably consistent with PMF, but with higher contribution from vehicular emissions (32%). Given the spatially large data set of PM sampled over an extended period, the study reconciles the results from previous work that showed only region- or season-specific aerosol components or sources contributing to PM ROS activity, possibly due to smaller sample sizes. Our results indicate that the ability to generate ROS is a generic property of fine PM to which almost all major emission sources contribute to variable extents. The ubiquitous nature of the ROS generation property of ambient particulate matter suggests widespread population exposures to aerosol components that have the ability to catalyze the production of oxidants in vivo.