Developing an instrument to quantify aerosol toxicity

Large-scale epidemiological studies have consistently shown that exposure to ambient particulate matter (PM) is responsible for a variety of adverse health effects. However, the specific physical and chemical properties of particles that are responsible for observed health effects, as well as the underlying mechanisms of particle toxicity upon exposure, remain largely uncertain. Studies have widely suggested that the oxidative potential (OP) of aerosol particles is a key metric to quantify particle toxicity. OP is defined as the ability of aerosol particle components to produce reactive oxidative species (ROS) and deplete antioxidants in vivo. Traditional methods for measuring OP using acellular assays largely rely on analyzing PM collected in filters offline. This is labor intensive and involves a substantial time delay between particle collection and OP analysis. It therefore likely underestimates particle OP, because many reactive chemical components which are contributing to OP are short-lived and therefore degrade prior to offline analysis. We investigated these differences in online and offline measurements with different acellular assays and with cellular methods and could show that for biogenic secondary organic aerosol (SOA), a large fraction decays within minutes to hours. Thus, new techniques are required to provide a robust and rapid quantification of particle OP, capturing the chemistry of oxidizing and short-lived highly reactive aerosol components and their concentration dynamics in the atmosphere. To address these measurement shortcomings, we developed a portable online instrument that directly samples particles into an ascorbic acid-based assay under physiologically relevant conditions of pH 6.8 and 37 °C, providing continuous accurate OP measurements with a high time resolution (5 min). This online oxidative potential ascorbic acid instrument (OOPAAI) runs autonomously for up to three days and has a detection limit of about 5 μg/m3 in an urban environ- ment, which allows the characterization of particle OP, even in low-pollution areas. With this novel instrument, we not only measured ambient aerosol, but also conducted various laboratory campaigns where we investigated the toxicity of various aerosol systems. Primary and secondary emissions with different aging times from car exhaust were measured and compared to primary and secondary aerosols from residential wood combustion, showing a higher toxicity for residential wood combustion for primary and secondary aerosols. Furthermore, we investigated the influence of transition metals like copper and iron on the OP of secondary organic aerosol. We could show that there is a synergistic effect for biogenic SOA with copper and for anthropogenic SOA with copper and iron, but an antagonistic effect with iron and biogenic SOA measured with the OOPAAI

Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants.

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2 and AH-) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH-  + O2 → Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104 and 4.7 × 104 M-2 s-1 for Fe(III) + AH2/AH- and 7.7 × 104 and 2.8 × 106 M-2 s-1 for Cu(II) + AH2/AH-, respectively

Atmospheric conditions and composition that influence PM2.5 oxidative potential in Beijing, China

Epidemiological studies have consistently linked exposure to PM2.5 with adverse health effects. The oxidative potential (OP) of aerosol particles has been widely suggested as a measure of their potential toxicity. Several acellular chemical assays are now readily employed to measure OP; however, uncertainty remains regarding the atmospheric conditions and specific chemical components of PM2.5 that drive OP. A limited number of studies have simultaneously utilised multiple OP assays with a wide range of concurrent measurements and investigated the seasonality of PM2.5 OP. In this work, filter samples were collected in winter 2016 and summer 2017 during the atmospheric pollution and human health in a Chinese megacity campaign (APHH-Beijing), and PM2.5 OP was analysed using four acellular methods: ascorbic acid (AA), dithiothreitol (DTT), 2,7-dichlorofluorescin/hydrogen peroxidase (DCFH) and electron paramagnetic resonance spectroscopy (EPR). Each assay reflects different oxidising properties of PM2.5, including particle-bound reactive oxygen species (DCFH), superoxide radical production (EPR) and catalytic redox chemistry (DTT/AA), and a combination of these four assays provided a detailed overall picture of the oxidising properties of PM2.5 at a central site in Beijing. Positive correlations of OP (normalised per volume of air) of all four assays with overall PM2.5 mass were observed, with stronger correlations in winter compared to summer. In contrast, when OP assay values were normalised for particle mass, days with higher PM2.5 mass concentrations (µgm−3) were found to have lower mass-normalised OP values as measured by AA and DTT. This finding supports that total PM2.5 mass concentrations alone may not always be the best indicator for particle toxicity. Univariate analysis of OP values and an extensive range of additional measurements, 107 in total, including PM2.5 composition, gas-phase composition and meteorological data, provided detailed insight into the chemical components and atmospheric processes that determine PM2.5 OP variability. Multivariate statistical analyses highlighted associations of OP assay responses with varying chemical components in PM2.5 for both mass- and volume-normalised data. AA and DTT assays were well predicted by a small set of measurements in multiple linear regression (MLR) models and indicated fossil fuel combustion, vehicle emissions and biogenic secondary organic aerosol (SOA) as influential particle sources in the assay response. Mass MLR models of OP associated with compositional source profiles predicted OP almost as well as volume MLR models, illustrating the influence of mass composition on both particle-level OP and total volume OP. Univariate and multivariate analysis showed that different assays cover different chemical spaces, and through comparison of mass- and volume-normalised data we demonstrate that mass-normalised OP provides a more nuanced picture of compositional drivers and sources of OP compared to volume-normalised analysis. This study constitutes one of the most extensive and comprehensive composition datasets currently available and provides a unique opportunity to explore chemical variations in PM2.5 and how they affect both PM2.5 OP and the concentrations of particle-bound reactive oxygen species

Iron and Copper Alter the Oxidative Potential of Secondary Organic Aerosol: Insights from Online Measurements and Model Development.

The oxidative potential (OP) of particulate matter has been widely suggested as a key metric for describing atmospheric particle toxicity. Secondary organic aerosol (SOA) and redox-active transition metals, such as iron and copper, are key drivers of particle OP. However, their relative contributions to OP, as well as the influence of metal-organic interactions and particulate chemistry on OP, remains uncertain. In this work, we simultaneously deploy two novel online instruments for the first time, providing robust quantification of particle OP. We utilize online AA (OPAA) and 2,7-dichlorofluoroscein (ROSDCFH) methods to investigate the influence of Fe(II) and Cu(II) on the OP of secondary organic aerosol (SOA). In addition, we quantify the OH production (OPOH) from these particle mixtures. We observe a range of synergistic and antagonistic interactions when Fe(II) and Cu(II) are mixed with representative biogenic (β-pinene) and anthropogenic (naphthalene) SOA. A newly developed kinetic model revealed key reactions among SOA components, transition metals, and ascorbate, influencing OPAA. Model predictions agree well with OPAA measurements, highlighting metal-ascorbate and -naphthoquinone-ascorbate reactions as important drivers of OPAA. The simultaneous application of multiple OP assays and a kinetic model provides new insights into the influence of metal and SOA interactions on particle OP

Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants.

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2 and AH-) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH-  + O2 → Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104 and 4.7 × 104 M-2 s-1 for Fe(III) + AH2/AH- and 7.7 × 104 and 2.8 × 106 M-2 s-1 for Cu(II) + AH2/AH-, respectively

Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants.

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2 and AH-) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH-  + O2 → Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104 and 4.7 × 104 M-2 s-1 for Fe(III) + AH2/AH- and 7.7 × 104 and 2.8 × 106 M-2 s-1 for Cu(II) + AH2/AH-, respectively

Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH2 and AH−) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH2/AH−  + O2 → Fe(III)/Cu(II) + H2O2 + products. Rate constants are 5.7 × 104 and 4.7 × 104 M−2 s−1 for Fe(III) + AH2/AH− and 7.7 × 104 and 2.8 × 106 M−2 s−1 for Cu(II) + AH2/AH−, respectively

Development of a Physiologically Relevant Online Chemical Assay To Quantify Aerosol Oxidative Potential

Large-scale epidemiological studies have shown a close correlation between adverse human health effects and exposure to ambient particulate matter (PM). The oxidative potential (OP) of ambient PM has been implicated in inducing toxic effects associated with PM exposure. In particular, reactive oxygen species (ROS), either bound to PM or generated by particulate components in vivo, substantially contribute to the OP and therefore toxicity of PM by lowering antioxidant concentrations in the lung, which can subsequently lead to oxidative stress, inflammation, and disease. Traditional methods for measuring aerosol OP are labor intensive and have poor time resolution, with significant delays between aerosol collection and ROS analysis. These methods may underestimate ROS concentrations in PM because of the potentially short lifetime of some ROS species; therefore, continuous online, highly time-resolved measurement of ROS components in PM is highly advantageous. In this work, we develop a novel online method for measuring aerosol OP based on ascorbic acid chemistry, an antioxidant prevalent in the lung, thus combining the advantages of continuous online measurement with a physiologically relevant assay. The method limit of detection is estimated for a range of atmospherically important chemical components such as Cu(II) 0.22 +/- 0.03 mu g m(3), Fe(II) 47.8 +/- 5.5 mu g m(-3), Fe(III) 0.63 +/- 0.05 mu g m(-3), and secondary organic aerosol 41.2 +/- 6.9 mu g m(-3), demonstrating that even at this early stage of development, the online method is capable of measuring the OP of PM in polluted urban environments and smog chamber studies