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Asian Journal of Atmospheric Environment - Vol. 15 , No. 1

[ Review Article ]
Asian Journal of Atmospheric Environment - Vol. 15, No. 1
Abbreviation: Asian J. Atmos. Environ
ISSN: 1976-6912 (Print) 2287-1160 (Online)
Print publication date 31 Mar 2021
Received 27 Nov 2020 Revised 17 Dec 2020 Accepted 08 Jan 2021

Oxidative Potential of Ambient PM and Related Health Endpoints over South Asia: A Review
Anil Patel ; Neeraj Rastogi*
Geosciences Division, Physical Research Laboratory, Ahmedabad-380009, India

Correspondence to : * Tel: +91 79 2631 4306 E-mail:

Copyright © 2021 by Asian Association for Atmospheric Environment
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


South Asia occupies only about 3.5% of the world’s area but, about 25% of the average world’s population lives here and is continuously exposed to severe air pollution. Unprecedented development activities in most of the South Asian cities emit primary and secondary pollutants into the atmosphere. Particulate matter (PM), a principal air pollutant, are tiny enough to remain suspended in the atmosphere for a long time (about a week). They can penetrate the human nasal airway and damage the lungs. PM effects on human health are assessed based on their mass concentration, size distribution, and chemical composition. Despite being critically important, studies related to PM effects on human health are limited over South Asia. In recent years, only a few South Asian research groups started studying the ability of atmospheric PM to cause human health hazards by generating in situ reactive oxygen species (ROS). The capability of atmospheric PM to produce ROS and/or deplete antioxidants is termed as their oxidative potential (OP). Though limited, efforts are made to identify particular species with the higher OP. Atmospheric aging of PM can also alter their OP. No studies from South Asia, except a few from India, investigated how the atmospheric aging changes the chemical and physical properties of PM and affect their OP over South Asia. These studies also showed that OP depends more on PM composition rather than its concentrations. Therefore, mitigation strategies for reducing PM mass concentrations alone may not be sufficient, and linking PM OP with significant health effects may be a better way to regulate specific sources of PM rather than overall PM mass. This review reports the necessities and limitations for PM OP studies in South Asia and future directions.

Keywords: Aerosols, Reactive oxygen species, Oxidative potential, Human health


There are a variable concentrations and chemical composition of particulate matter (PM) in the Earth’s atmosphere, with their size ranging from a few nm to several μm. They interact with the respiratory system of all living organisms. The majority of ambient atmospheric species are injected into the atmosphere by several natural sources (e.g., mineral dust, sea-salts, volcanic emissions, forest fires, etc.) (Fig. 1). Most of the natural gaseous and particulates species we breathe today are similar to what respired by our ancestors. After the pre-industrial era, anthropogenic activities started pumping a large pool of toxic and redox-active species into the atmosphere via industrialization and urbanization, which started deteriorating the ambient air quality (Akatsu, 2015). Ambient PM (or aerosols) are the reactive as well as non-reactive species including organic carbon (OC), elemental carbon (EC), major inorganic ions, trace and heavy metals, etc., in variable sizes (Seinfeld and Pandis, 2006). Fig. 1 depicts a schematic representation of sources of atmospheric PM and their reach in the human body where they can generate reactive oxygen species and affect human health. Assessing the effects of PM on Earth’s climate and human health is among major current research focus worldwide (Pöschl, 2005). The emission sources of PM and meteorological conditions over different regions vary drastically and thus, their concentrations and composition also show a large spatiotemporal variability. PM retain in the lower troposphere for about a week, depending upon their physiochemical properties and meteorological conditions. However, particles emitted at one place, depending upon the wind speed and wind direction, can travel thousands of kilometers before they get removed from the atmosphere. Thus, the toxic emissions in one place can affect many distant places downwind. During the longrange transport of PM, aging processes such as homogeneous and heterogeneous reactions, condensation, coagulation, evaporation, aggregation, oxidation, reduction, etc., may enhance/reduce particle toxicity (Pöschl, 2005).

Fig. 1. 
A schematic representation of sources of atmospheric PM and their reach in the human body where they can generate reactive oxygen species and affect human health.

PM mass concentrations are usually reported in microgram of PM per cubic meter of air (μg m-3). The average adult inhales about 17 m3 of air daily (~11.8 lpm) (Brochu, 2006). The amount of PM reaching the human respiratory system depends upon the ambient PM concentration levels, as a fraction of PM gets trapped in the system (Lyu et al., 2018; Fang et al., 2017; Oberdorster et al., 2005). Human exposure to an environment with PM mass concentration higher than defined safe limits may result in chronic health problems (Pope et al., 2020; Delfino et al., 2006; Oberdörster et al., 2005). Millions of death have been recorded worldwide due to fine PM exposure only, as shown by world health statistics - 2018 (Burnett et al., 2014). However, the PM toxicity cannot be explained in terms of merely the amount of dose; rather, it depends upon the physicochemical properties of particles present in the dose (Patel et al., 2021; Patel and Rastogi, 2020; Borlaza et al., 2018; Charrier et al., 2016; Valavanidis et al., 2008). PM induced oxidative stress in human is one of the widely accepted mechanisms. It occurs when the defense mechanisms cannot control the enhanced level of oxidants produced by the PM in the human body. These oxidants are nothing but reactive oxygen species (ROS). Biologically relevant ROS members include but not limited to moderately reactive superoxide (O2 ·-), less reactive hydrogen peroxide (H2O2), and highly reactive hydroxyl radical (·OH). On inhalation, atmospheric redox-active PM species interact with cells, such as macrophages, and produce ROS (Fig. 1). In this process, redox-active PM species such as transition metals and quinones catalytically transfer an electron from biological reducing respiratory complexes, e.g., reduced forms of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), to the molecular oxygen (O2) (Kumagai et al., 1997). In situ ROS formation is the sequential univalent reduction of the O2. The capacity of PM to deplete anti-oxidants and/ or oxidize the electron-rich enzymes through generating ROS in the human body is known as their ‘oxidative potential (OP)’, a metric of PM induce toxicity (Bates et al., 2019). Further, NADH and NADPH enzymes are essential for maintaining a vast array of biological processes, and their deficiency or imbalance are associated with many pathological disorders (Xiao et al., 2018).

The O2 ·- formation depends upon the cellular oxygen concentration. Mitochondria is so far known as one of the most suspicious places where the in vivo ROS generation occurs. Lungs are mostly affected by ROS due to their direct contact with the atmospheric oxygen. Particularly in tissues not exposed to O2 , the in vivo ROS production is likely to be smaller due to insufficient mitochondrial oxygen concentration (Turrens, 2003). Sometimes, however, hyperbaric conditions dissolve more oxygen in blood plasma, resulting in a hyperoxic environment. In this circumstance, the size of PM and their retention time in the human respiratory tract define the actual cytotoxicity (Oberdörster et al., 2005). In contrast to the larger size PM, ultrafine PM have accessibility to the blood stream by different transfer routes and mechanisms, thereby reaching almost any organ in our body, including the brain and heart (Terzano et al., 2010). In the hyperoxic environment, the brain is the most suspicious organ to show elevated levels of ROS (Turrens, 2003).

The present article reviews the current status of the work reported on the PM OP, and how it interacts with biological tissues in the human body over the different regions of South Asia. It also discusses the limitations and future directions for PM OP studies in South Asia.


Among several assays available in the literature for measuring PM OP, the majority measures the potential of PM to produce ROS (i.e., endogenous ROS, also known as OP). In contrast, a few assays measure PM-bound ROS concentration (exogenous ROS). These assays are nicely summarized in a recent study (Bates et al., 2019). These assays can be acellular (cell-free) or cellular.

2. 1 Acellular Assays

A variety of acellular assays such as dithiothreitol (DTT, Cho et al., 2005), Glutathione (GSH, Shahpoury et al., 2019), Ascorbic Acid (AA, Fang et al., 2016), Electron Spin Resonances (ESR, Yang et al., 2014), Chemiluminescent Reductive Acridinium Triggering (CRAT, Yang et al., 2014), etc, are employed for assessing the PM induce ROS. However, each of these assays has a different sensitivity to the various PM components that produce ROS, and none respond to all such components. The degrees of their reactivity with PM vary from assay to assay (Bates et al., 2019 and references therein). For example, DTT oxidation is executed by redox-active PM that further reduces O2 to produce ROS. DTT assay responds to a pool of components that include a few metals and organic components; however, the role of Fe in the DTT assay is debatable (Bates et al., 2019; Charrier and Anastasio, 2012).

On the contrary, Rao et al. (2020) and Bates et al. (2019) reviewed that other assays such as AA, GSH usually measure the capability of metals present in PM to deplete antioxidants with the adverse response to organic components. ESR assay measures the capacity of PM to induce ·OH, and it responds well to metals. CRAT has a high selectivity for superoxide ion, and it responds to ferric and cupric ions and organic species, such as quinones (Yang et al., 2014). At present, no single acellular assay can assess the OP of all the toxic PM species; however, it would be nice to have one.

2. 2 Cellular Assays

Cell-based assays such as dichloro-dihydro-fluorescein diacetate (DCFH-DA, Venkatachari et al., 2005), and p-hydroxyphenyl acetic acid (POPHAA) dimerization (Hasson and Paulson, 2003) measures the particle-bound ROS, i.e., equivalent H2O2 concentration. Furthermore, Wardman (2007) reviewed several fluorescent and luminescent probes such as dichlorodihydrofluorescein, dihydrorhodamine, hydroethidine, etc., for the measurement of oxidative and nitrosative species in cells and tissues. However, dichlorodihydrofluorescein and dihydrorhodamine are shown to be unreactive towards superoxide ion, and less reactive towards the H2O2, a dismutation product. Further, background oxidation of H2O2 by metal impurities such as Fe (Fenton reaction) in the buffer solution can influence the outcomes; hence, chelating treatment to buffer solution before the reaction is performed (Shen and Anastasio, 2011).

Further, these probes require a catalyst for the reaction. As none of these assays cover the entire range of ROS family, it is better to measure the capability of PM to generate ROS (i.e., OP), rather than measuring the concentration of ROS. Among all the OP assays developed so far, the DTT assay is widely used because it responds to many organic components and trace metals (Charrier and Anastasio, 2012). The response of DTT assay also correlates well with a pool of biological endpoints such as hemeoxygenase-1 (HO-1) expression (Li et al., 2003), a reduction activity of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (Steenhof et al., 2011), a fraction of nitric oxide in exhaled breath (Delfino et al., 2013), markers of the airway and nasal inflammation ( Janssen et al., 2015), increased relative risk for asthma (Yang et al., 2016; Bates et al., 2015), and congestive heart failure (Bates et al., 2015). Thus, a general conceptual framework of the toxicity associated with PM sources and emission characteristics can be represented by DTT-based PM OP. However, the development of one probe covering all the ROS is the need of the hour.


South Asia covers only 11.6% of the Asian continents and 3.5% of the world’s land but, this region accounts for ~40% and ~25% of Asia’s and world’s population, respectively. The population density of the South Asian region is ~10 times higher than the average population density of the world (Demographia, 2020). Moreover, India is among the fastest-growing economies of the world (Subramanian 2019), and occupies ~60% of the land area of the South Asian region along with ~12% higher population density. Besides, a variety of anthropogenic emissions are increasing unprecedently in several metropolitan cities of the developing countries of South Asia, which violate the international air quality standards (Marlier et al., 2016; WHO, 2016; Brauer et al., 2012; Gautam, 2010; Nandasena et al., 2010). Winter conditions usually cause an unhealthy accumulation of particulates in the lower troposphere for an extended period of stagnation in many regions (Singh et al., 2021). Wind transport can harm rural areas downwind. Despite being a hotspot, studies reporting PM composition and OP together over South Asia are despicably low.

3. 1 Link between PM Composition and OP over South Asia

In recent years, a very few groups from India reported the PM chemical composition along with its DTT-based OP (DTT-OP) over different regions dominated by various emission sources and/or meteorological conditions (Patel et al., 2021; Patel and Rastogi, 2020, 2018a, 2018b; Puthussery et al., 2020; Yadav et al., 2019; Rastogi and Patel, 2017; Vreeland et al., 2016). Though limited, these studies covered many important aspects including DTT-OP near to point source emission like trash burning (Vreeland et al., 2016), seasonal variation and the effect of long-range transport of aerosols on chemical composition and DTT-OP over a mountain (Patel and Rastogi, 2018b) and an ocean (Patel and Rastogi, 2020), DTT-OP from mixed sources over big cities (Patel et al., 2021; Puthussery et al., 2020; Yadav et al., 2019), and the plausible effect of meteorology (e.g., fog) on the chemical composition and DTT-OP over a semi-arid site (Patel and Rastogi, 2018a). Recently, Ahmad et al. (2021) reported DTTOP over Lahore and Peshawar in Pakistan. PM mass and related volume-normalized and mass-normalized DTTOP reported by these studies are depicted in Fig. 2.

Fig. 2. 
Dithiothreitol (DTT)-based average volume-normalized oxidative potential (OPV, color scale) and average mass-normalized oxidative potential (OPM, size of bubbles) over South Asia. 1Patiala; Patel and Rastogi, 2018a, 2New Delhi; Puthuserry et al., 2020, 3Mount Abu; Patel and Rastogi, 2018b, 4Ahmedabad; Patel et al., 2021, 5Mumbai; Yadav et al., 2019, 6Banglore; Vreeland et al., 2016, 7Arabian Sea; Patel and Rastogi, 2020, 8Lahore and Peshawar, Ahmad et al., 2021.

Vreeland et al. (2016) reported the OP of extremely high concentrations of redox-active organic aerosols (mainly aromatic di-acids from plastic burning and levoglucosan from biomass burning) emitted from the roadside trash burning in Bangalore, India. The dose (volume- normalized DTT-OP) reaching the people passing by or living near to the trash burning location was significantly higher, as predicted, compared to the ambient samples, evidencing a significant public health hazard. However, organic carbon (OC) mass-normalized OP in samples collected near trash burning was lower than those for ambient PM samples. After two years of that study, through a laboratory experiment, our group reported that secondary inorganic aerosols (SIA, the sum of NH4+, NO3- and SO42-) do not respond to DTT-activity (Patel and Rastogi, 2018a). Thus, the mass-normalized OP can be significantly biased if there is a relatively similar or higher SIA fraction than water-soluble redox-active organic species in the ambient PM over a given study region. Patel and Rastogi (2018a) proposed to use variation in mass-normalized DTT-OP along with the WSOC/ SIA ratio to overcome the bias introduced by SIA. The same study also reported that the biomass burning derived carbonaceous aerosols in PM2.5 have higher OP than those derived from fossil fuel combustion. In the same year, seasonal variability in PM10 chemical composition and DTT-OP was reported over Mount Abu, a high altitude site in western India (Patel and Rastogi, 2018b). The highest PM10 mass during pre-monsoon over Mount Abu was ascribed to high dust loading from the surrounding Desert and Arab continents. However, the corresponding DTT-OP (both volume- and massnormalized) was not higher in the pre-monsoon season. It was reported that anthropogenically emitted pollutants transported by the northeasterly air-masses were dominant during post-monsoon, and found to be associated with the highest DTT-OP (both volume- and mass-normalized). After that, a study from the same group over the marine environment (the Arabian Sea) observed that DTT-OP (both volume- and mass-normalized) of PM10 associated with the air-masses traveled from the Indian subcontinent was higher compared to PM10 traveled from the marine and desert environments, depicting the role of anthropogenic emission on the PM toxicity (Patel and Rastogi, 2020). These observations highlighted the poor reactivity of the dust components of PM10 with the DTT. Interestingly, EC mass fraction in PM2.5 over Patiala (Patel and Rastogi, 2018a), and in PM10 over Mount Abu (Patel and Rastogi, 2018b) and the Arabian Sea (Patel and Rastogi, 2020) was found to be positively correlated with mass-normalized DTT-OP (p<0.05). The slope from this linear relationship over different regions highlighted that atmospheric aging of species emitted along with EC makes them more DTT-active, as both the Arabian Sea and Mount Abu predominantly receive aged aerosols. A recent study by our group reported OP and a variety of chemical speciation of PM10 at the five sites representing different environments of a big city (Ahmedabad) in western India (Patel et al., 2021). These sites include near traffic junction, bus transport hub, industrial,and two types of residential area in Ahmedabad. Narol, an industrial site, expectedly yielded the highest volumenormalized DTT-OP, highlighting a higher risk to Narol’s inhabitants from potentially redox-active PM10 species. One of the interesting features was that volume-normalized DTT-OP varied with PM10 mass, but mass-normalized DTT-OP remained similar from site-to-site. As inferred from the optical properties of PM10, nitrogenous organic compounds mainly emitted from the traffic-related sources in Ahmedabad have higher OC mass-normalized OP. Yadav et al. (2019) reported that volumenormalized DTT-OP for indoor PM2.5 emitted from the combustion of crop residue, firewood, mixed, and biomass fuel was an order of magnitude higher than ambient PM2.5. Further, a recent study by Puthussery et al. (2020) reported the real-time measurement of DTT-OP in PM2.5 over New Delhi, India. They found that photochemically aged organic aerosols (OA) mostly drove the DTT-activity, whereas fresh PM2.5 emitted from vehicles showed less influence on OP. Further, Yu et al. (2018) reported that there are elements in the PM components with synergistic and antagonistic effects in generating ROS based on the DTT assay, which also needs to be understood over South Asia. Ahmad et al. (2021), the only study on DTT-OP from Pakistan, reported that relatively higher fraction of carbonaceous aerosols and metals in PM2.5 over Peshawar could be the reason for observed high DTT-based mass-normalized OP compared to that found over Lahore. Despite drastically different volumenormalized DTT-OP over Patiala (3.8 nmol DTT min-1 m-3, India) and Peshawar (9.3 nmol DTT min-1 m-3, Pakistan), mass-normalized DTT-OP was similar (Fig. 2). Such observations highlight that the PM OP over these nearby locations were not similar. Further, the another study from Lahore during 2007-2008 investigated DCFH-DA-based ROS-activity of water-soluble fine and coarse PM with the highest activity in fall and midlate winter (Shafer et al., 2010). The findings showed that the water-soluble Cu, Mo, Fe, and Ni are the most potential ROS-active metals.

3. 2 PM and Heath of Biological Tissues in the Human Body over South Asia

A few studies from India investigated the role of PM exposure on the health of biological tissues using a variety of markers listed in Table 1 (Das et al., 2021; Jan et al., 2020; Roy et al., 2015; Sambandam et al., 2015; Dutta et al., 2013, 2012; Banerjee et al., 2012; Mondal et al., 2011; Rahman et al., 1997; Arif et al., 1992). Here, Arif et al. (1992) and Rahman et al. (1997) investigated the toxic potential of various particles and fibers to the human and rat alveolar macrophages. They found that alveolar macrophages in humans produce more ROS compare to that in rats. A group from Chittaranjan National Cancer Institute investigated the role of PM in deoxyribonucleic acid (DNA) single-strand damage on pre-menopausal women who were engaged in cooking using bio-fuel/ bio-mass in rural areas of West Bengal, India (Mondal et al., 2011). They observed a sharp rise in DNA singlestrand breaks in Buccal Epithelial Cells (BECs), which was positively associated with the ROS generation and PM levels, indicating oxidative stress resulted from biomass smoke. Similar type of studies were reported from West Bengal, wherein blood sample and sputum samples were measured for several health indicators including serum Interleukin-6 (IL-6), IL-8 by Enzyme-linked immunosorbent assay (ELISA), Tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) from the women using biomass and compared with the women using cleaner fuel (as a control) (Dutta et al., 2013; Dutta et al., 2012). ROS generation, depletion of superoxide dismutase (SOD), and indoor concentration of PM were also measured. Biomass users had more indoor air pollutants compared to controlled one and their serum as well as sputum contained significantly elevated levels of the biological markers of inflammation, oxidative stress and hypertension such as IL-6, IL-8, TNF-α and CRP, and ROS generation; while SOD was depleted significantly. If the damage is not repaired, it may lead to several health problems, including cancer (Moustacchi, 2000).

Table 1. 
Overview of ROS and their role in human health over South Asia.
Study Site and exposure Assays for Reactive Oxygen Species Biological markers
Arif et al., 1992 and Rahman et al., 1997 India; Particles and Fibers Luminol dependent and peroxide dependent chemiluminescence assays for ROS Human and rat alveolar macrophages
Mondal et al., 2011 India; Biomass smoke_85 premenopausal women from rural areas of West Bengal ROS by flow cytometry and superoxide dismutase (SOD) by spectrophotometry Comet assay for DNA single-strand breaks in Buccal Epithelial Cells (BECs)
Dutta et al., 2012, 2013 India; Biomass smoke_Blood sample and Sputum sample ROS by flow cytometry and SOD by spectrophotometry Serum interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) were measured by Enzyme-linked immunosorbent assay (ELISA)
Pant et al., 2015 India; Oxidative potential of PM10 fraction of road dust in New Delhi Depletion of Ascorbic acid (AA) and Glutathione (GSH) -
Roy et al., 2015 India; Urban and rural indoor environment in Pune DTT assay Plasmid DNA assay
Sambandam et al., 2015 India; Respirable coal fly ash from power plant chimneys Depletion of GSH and ROS generation using DCFH-DA assay DNA fragmentation assay, MTT assay
Jan et al., 2020 India; Atmosphere of Pune DCFH-DA assay MTT assay and % haemolysis of human red blood cells
Das et al., 2021 India; Atmosphere of Delhi DCFH-DA assay MTT assay, IL-6, IL-8

Furthermore, a study from the urban and rural indoor environment in Pune, India, demonstrated the significant role of fine metals in the DTT oxidation and DNA damage, highlighting the importance of PM size in the indoor environment’s toxicological mechanism (Roy et al., 2015). After that, the positive effects of respirable coal fly ash, collected from power plant chimneys in Chennai, India, on the induced in vitro toxicity in different cell-lines were examined by DNA fragmentation assay, MTT assay, depletion of GSH, and ROS generation using DCFH-DA assay (Sambandam et al., 2015). Moreover, a group from Pune University, India, carried out a study to asses the toxicological effects in the human body due to metals present in the atmosphere of Pune. They studied the response of various biological markers, including the cytotoxicity profiles measured by MTT assay on two different cell lines (epithelial cell line and human peripheral blood mononuclear cells) and % haemolysis of human red blood cells on exposure to different concentration of PM (Jan et al., 2020). In addition, ROS measured using DCFH-DA in both cell lines were also found to be increasing with exposed PM mass concentration. Das et al. (2021) showed a year-long PM2.5-metals catalyzed ROS generation by DCFH-DA assay along with toxicological parameters at Delhi, the hotspot for air pollution in India. A higher fraction of trace metals in post-monsoon and winter caused lower cell-viability in contrast to the pre-monsoon and monsoon periods. However, the PM2.5 during pre-monsoon and winter were associated with higher ROS generation compared to the rest two seasons. This highlights that the metals damaging the cells are not the same which actually produce ROS in human body.


It is indeed disappointing to notice that none of the studies related to health endpoints discussed above measured the complete PM composition, including the speciation of organic carbon, which is reported to be a highly responsive component for ROS generation in the human body (through redox-cycling of quinone type species). Further, the most of such studies reported over South Asia were carried out either in the indoor environments or near the source locations. However, the PM OP can be affected by several factors including photochemical aging, volatility, and pH of PM, and ambient meteorological conditions (Bates et al., 2019 and references therein). On the other hand, the majority of the OP based studies carried out over regions dominated by different sources and meteorological conditions in outdoor environments did not consider any health endpoints. It is a compulsive requirement to provide a complete scenario of PM induce health effects in time and space over South Asia.

Further, such studies are virtually lacking in other South Asian countries such as Pakistan, Afghanistan, Nepal, Bhutan, Bangladesh, Sri Lanka, and Maldives. Several studies have reported air pollution as the potential risk factor for cardiovascular disease over India (Balakrishnan et al., 2019; Dutta and Ray, 2013; Nautiyal et al., 2007; Cropper et al., 1991), Nepal (Adhikari et al., 2020), Sri Lanka (Nandasena et al., 2010), Afghanistan (Rana et al., 2019; Falvo et al., 2015) and Pakistan (Sughis et al., 2012). However, none of these studies discussed specific species responsible for the pollution-borne diseases and the mechanism behind it. Yamamoto et al. (2014) made an effort to review air pollution as a risk factor for morbidity and mortality in South Asia; however, there was a bias as all of the studies were from India only.

As mentioned earlier, the OP is one of the most conspicuous health indicators for PM induced health effects in humans. A significant criticism of the studies that have modeled OP and associated health endpoints can be explained by the fact that PM composition varies drastically in time and space and thus their relation with OP shall also vary (Fang et al., 2016; Bates et al., 2015). It is vital to start assessing PM OP at least over selected strategic sites (e.g., megacities, rural areas, mountains, islands) dominated by different sources and/or meteorological conditions in South Asia. It is also crucial to characterize the PM chemical composition temporally and spatially along with their OP using different cellular and acellular assays, as no assay covers the entire PM components. It would be nice to develop a single acellular assay that responds to all the toxic species present in the ambient PM. In addition, the measurements of various biological markers that express the oxidative stress and other health endpoints should also be taken into account while considering the PM toxicity over South Asia. The involvement of epidemiologists and medical researchers with atmospheric scientists is critical to understand the underlying mechanisms of PM induced health effects.

It is worth mentioning that PM mass can be similar at multiple sites and/or at one location at different times. But, PM composition is highly variable in time and space as it strongly depends upon the emission sources, meteorological parameters, and atmospheric processing, and this fact cannot be ignored (Patel et al., 2021; Patel and Rastogi, 2020, 2018a, 2018b; Verma et al., 2015; Li et al., 2009). Further, there are elements in the PM components with synergistic and antagonistic effects in generating ROS, and they need to be understood over South Asia. Recommended studies will be crucial in designing/ developing mitigation strategies to reduce/stop the emissions of specific species that have a significant role in the oxidative burden. Reduction of PM mass concentrations alone may not be sufficient for better air quality for human health.

1. Adhikari, S., Mahapatra, P.S., Pokheral, C.P., Puppala, S.P. (2020) Cookstove smoke impact on ambient air quality and probable consequences for human health in rural locations of southern Nepal. International Journal of Environmental Research and Public Health, 17(550), 1-21.
2. Ahmad, M., Yu, Q., Chen, J., Cheng, S., Qin, W., Zhang, Y. (2021) Chemical characteristics, oxidative potential, and sources of PM2.5 in wintertime in Lahore and Peshawar, Pakistan. Journal of environmental sciences, 102, 148-158.
3. Akatsu, M. (2015) Chapter 4 - The Problem of Air Pollution During the Industrial Revolution: A Reconsideration of the Enactment of the Smoke Nuisance Abatement Act of 1821. Monograph Series of the Socio-Economic History Society, Japan, pp. 85-109.
4. Arif, J.M., Khan, S.C., Aslam, M., Mahmood, N., Rahman, Q. (1992) Diminution in Kerosene-Mediated Induction of Drug Metabolizing Enzymes by Asbestos in Rat Lungs. Pharmacology & Toxicology, 71(1), 37-40.
5. Balakrishnan, K., Dey, S., Gupta, T., Dhaliwal, R.S., Brauer, M., Cohen, A.J., Stanaway, J.D., Beig, G., Joshi, T.K., Aggarwal, A.N., Sabde, Y., Sadhu, H., Frostad, J., Causey, K., Godwin, W., Shukla, D.K., Kumar, G.A., Varghese, C.M., Muraleedharan, P., Agrawal, A., Anjana, R.M., Bhansali, A., Bhardwaj, D., Burkart, K., Cercy, K., Chakma, J.K., Chowdhury, S., Christopher, D.J., Dutta, E., Furtado, M., Ghosh, S., Ghoshal, A.G., Glenn, S.D., Guleria, R., Gupta, R., Jeemon, P., Kant, R., Kant, S., Kaur, T., Koul, P.A., Krish, V., Krishna, B., Larson, S.L., Madhipatla, K., Mahesh, P.A., Mohan, V., Mukhopadhyay, S., Mutreja, P., Naik, N., Nair, S., Nguyen, G., Odell, C.M., Pandian, J.D., Prabhakaran, D., Prabhakaran, P., Roy, A., Salvi, S., Sambandam, S., Saraf, D., Sharma, M., Shrivastava, A., Singh, V., Tandon, N., Thomas, N.J., Torre, A., Xavier, D., Yadav, G., Singh, S., Shekhar, C., Vos, T., Dandona, R., Reddy, K.S., Lim, S.S., Murray, C.J.L., Venkatesh, S., Dandona, L. (2018) The impact of air pollution on deaths, disease burden, and life expectancy across the states of India: the Global Burden of Disease Study 2017. Lancet Planet Health, December 6.
6. Banerjee, A., Mondal, N.K., Das, D., Ray, M.R. (2012) Neutrophilic Infl ammatory Response and Oxidative Stress in Premenopausal Women Chronically Exposed to Indoor Air Pollution from Biomass Burning. Inflammation, 35(2), 671- 683.
7. Bates, J.T., Fang, T., Verma, V., Zeng, L., Weber, R.J., Tolbert, P.E., Abrams, J.Y., Sarnat, S.E., Klein, M., Mulholland, J.A., Russell, A.G. (2019) Review of Acellular Assays of Ambient Particulate Matter Oxidative Potential: Methods and Relationships with Composition, Sources, and Health Effects. Environmental Science and Technology, 53(8), 4003-4019.
8. Bates, J.T., Weber, R.J., Abrams, J., Verma, V., Fang, T., Klein, M., Strickland, M.J., Sarnat, S.E., Chang, H.H., Mulholland, J.A., Tolbert, P.E., Russell, A.G. (2015) Reactive Oxygen Species Generation Linked to Sources of Atmospheric Particulate Matter and Cardiorespiratory Effects. Environmental Science and Technology, 49(22), 13605-13612.
9. Borlaza, L.J.S., Cosep, E.M.R., Kim, S., Lee, K., Joo, H., Park, M., Bate, D., Cayetano, M.G., Park, K. (2018) Oxidative potential of fine ambient particles in various environments. Environmental Pollution, 243(Pt B), 1679-1688.
10. Brauer, M., Amann, M., Burnett, R.T., Cohen, A., Dentener, F., Ezzati, M., Henderson, S.B., Krzyzanowski, M., Martin, R.V., Van Dingenen, R., Van Donkelaar, A., Thurston, G.D. (2012) Exposure assessment for estimation of the global burden of disease attributable to outdoor air pollution. Environmental Science and Technology, 46(2), 652-660.
11. Brochu, P., Ducré-Robitaille, J.F., Brodeur, J. (2006) Physiological Daily Inhalation Rates for Free-Living Individuals Aged 1 Month to 96 Years, Using Data from Doubly Labeled Water Measurements: A Proposal for Air Quality Criteria, Standard Calculations and Health Risk Assessment. Human and Ecological Risk Assessment: An International Journal, 12(4), 675-701.
12. Burnett, R.T., Iii, C.A.P., Ezzati, M., Olives, C., Lim, S.S., Mehta, S. (2014) An Integrated Risk Function for Estimating the Global Burden of Disease Attributable to Ambient Fine Particulate Matter Exposure. Environmental Health Perspectives, 122(4), 397-404.
13. Charrier, J.G., Anastasio, C. (2012) On dithiothreitol (DTT) as a measure of oxidative potential for ambient particles: Evidence for the importance of soluble transition metals. Atmospheric Chemistry and Physics, 12(5), 11317-11350.
14. Charrier, J.G., McFall, A.S., Vu, K.K.-T., Baroi, J., Olea, C., Hasson, A., Anastasio, C. (2016) A bias in the “mass-normalized” DTT response - An effect of non-linear concentration-response curves for copper and manganese. Atmospheric Environment, 144, 325-334.
15. Cho, A.K., Sioutas, C., Miguel, A.H., Kumagai, Y., Schmitz, D.A., Singh, M., Eiguren-Fernandez, A., Froines, J.R. (2005) Redox activity of airborne particulate matter at different sites in the Los Angeles Basin. Environmental Research, 99, 40-47.
16. Cropper, M.L., Simon, N.B., Alberini, A., Sharma, P.K. (1991) The Health Effects of Air Pollution in Delhi, India. National Capital Territory of Delhi. Policy Research Working Papers. The World Bank. December 1991.
17. Das, A., Habib, G., Vivekanandan, P., Kumar, A. (2021) Reactive oxygen species production and in fl ammatory effects of ambient PM2.5-associated metals on human lung epithelial A549 cells “one year-long study”: The Delhi chapter. Chemosphere, 262, 128305.
18. Delfino, R.J., Staimer, N., Gillen, D., Tjoa, T., Sioutas, C., Fung, K., George, S.C., Kleinman, M.T. (2006) Personal and ambient air pollution is associated with increased exhaled nitricoxide in children with asthma. Environmental Health Perspectives, 114(11), 1736-1743.
19. Delfino, R.J., Staimer, N., Tjoa, T., Gillen, D.L., Schauer, J.J., Shafer, M.M. (2013) Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel. Journal of Exposure Science and Environmental Epidemiology, 23(5), 466-473.
20. Demographia (2020) Demographia World Urban Areas.
21. Dutta, A., Ray, M.R. (2013) Increased cardiovascular risk due to systemic inflammatory changes and enhanced oxidative stress in urban Indian women. Air Quality, Atmosphere & Health, 6, 501-508.
22. Dutta, A., Ray, M.R., Banerjee, A. (2012) Systemic inflammatory changes and increased oxidative stress in rural Indian women cooking with biomass fuels. Toxicology and Applied Pharmacology, 261(3), 255-262.
23. Dutta, A., Roychoudhury, S., Chowdhury, S., Ray, M.R. (2013) Changes in sputum cytology, airway inflammation and oxidative stress due to chronic inhalation of biomass smoke during cooking in premenopausal rural Indian women. International Journal of Hygiene and Environmental Health, 216(3), 301-308.
24. Falvo, M.J., Osinubi, O.Y., Sotolongo, A.M., Helmer, D.A. (2015) Airborne hazards exposure and respiratory health of Iraq and Afghanistan veterans. Epidemiologic Reviews, 37, 116-130.
25. Fang, T., Verma, V., Bates, J.T., Abrams, J., Klein, M., Strickland, J.M., Sarnat, E.S., Chang, H.H., Mulholland, A.J., Tolbert, E.P., Russell, G.A., Weber, J.R. (2016) Oxidative potential of ambient water-soluble PM2.5 in the southeastern United States: Contrasts in sources and health associations between ascorbic acid (AA) and dithiothreitol (DTT) assays. Atmospheric Chemistry and Physics, 16, 3865-3879.
26. Fang, T., Zeng, L., Gao, D., Verma, V., Stefaniak, A.B., Weber, R.J. (2017) Ambient Size Distributions and Lung Deposition of Aerosol Dithiothreitol-Measured Oxidative Potential: Contrast between Soluble and Insoluble Particles. Environmental Science & Technology, 51(12), 6802-6811.
27. Gautam, D.R. (2010) Air Pollution: Its causes and consequences with reference to kathmandu metropolitan city. The Third Pole, 8(10), 27-33.
28. Hasson, A.S., Paulson, S.E. (2003) An investigation of the relationship between gas-phase and aerosol-borne hydroperoxides in urban air. Journal of Aerosol Science, 34(4), 459- 468.
29. Jan, R., Roy, R., Bhor, R., Pai, K., Satsangi, P.G. (2020) Toxicological screening of airborne particulate matter in atmosphere of Pune: Reactive oxygen species and cellular toxicity. Environmental Pollution, 261, 113724.
30. Janssen, N.A.H., Strak, M., Yang, A., Hellack, B., Kelly, J.F., Kuhlbusch, A.J.T., Harrison, M.R., Brunekreef, B., Cassee, R.F., Steenhof, M., Hoek, G. (2015) Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers. Occupational and Environmental Medicine, 72(1), 49-56.
31. Kumagai, Y., Arimoto, T., Shinyashiki, M., Shimojo, N., Nakai, Y., Yoshikawa, T., Sagai, M. (1997) Generation of reactive oxygen species during interaction of diesel exhaust particle components with NADPH-cytochrome P450 reductase and involvement of the bioactivation in the DNA damage. Free Radical Biology and Medicine, 22(3), 479-487.
32. Li, N., Sioutas, C., Cho, A., Schmitz, D., Misra, C., Sempf, J., Wang, M., Oberley, T., Froines, J., Nel, A. (2003) Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environmental Health Perspectives, 111(4), 455-460.
33. Li, Q., Wyatt, A., Kamens, R.M. (2009) Oxidant generation and toxicity enhancement of aged-diesel exhaust. Atmospheric Environment, 43(5), 1037-1042.
34. Lyu, Y., Guo, H., Cheng, T., Li, X. (2018) Particle Size Distributions of Oxidative Potential of Lung-Deposited Particles: Assessing Contributions from Quinones and Water-Soluble Metals. Environmental Science & Technology, 52(11), 6592-6600.
35. Marlier, M.E., Jina, A.S., Kinney, P.L., Defries, R.S. (2016) Extreme Air Pollution in Global Megacities. Current Climate Change Reports, 2, 15-27.
36. Mondal, N.K., Bhattacharya, P., Ray, M.R. (2011) Assessment of DNA damage by comet assay and fast halo assay in buccal epithelial cells of Indian women chronically exposed to biomass smoke. International Journal of Hygiene and Environmental Health, 214(4), 311-318.
37. Moustacchi, E. (2000) DNA damage and repair: Consequences on dose-responses. Mutation Research, 464(1), 35-40.
38. Nandasena, Y.L.S., Wickremasinghe, A.R., Sathiakumar, N. (2010) Air pollution and health in Sri Lanka: A review of epidemiologic studies. BMC Public Health, 10, 300.
39. Nautiyal, J., Garg, M.L., Kumar, M.S., Khan, A.A., Thakur, J.S., Kumar, R. (2007) Air Pollution and Cardiovascular Health in Mandi-Gobindgarh, Punjab, India - A Pilot Study. International Journal of Environmental Research and Public Health, 4(4), 268-282.
40. Oberdörster, G., Oberdörster, E., Oberdörster, J. (2005) Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives, 113(7), 823-839.
41. Patel, A., Rastogi, N. (2020). Chemical Composition and Oxidative Potential of Atmospheric PM10 over the Arabian Sea. ACS Earth and Space Chemistry, 4(1), 112-121.
42. Patel, A., Rastogi, N. (2018a) Oxidative potential of ambient fine aerosol over a semi-urban site in the Indo-Gangetic Plain. Atmospheric Environment, 175(February), 127-134.
43. Patel, A., Rastogi, N. (2018b) Seasonal variability in chemical composition and oxidative potential of ambient aerosol over a high altitude site in western India. Science of The Total Environment, 644(December), 1268-1276.
44. Patel, A., Rastogi, N., Gandhi, U., Khatri, N. (2021) Oxidative potential of atmospheric PM10 at five different sites of Ahmedabad, a big city in Western India. Environmental Pollution, 268(Part B), 115909.
45. Pope, C.A., Coleman, N., Pond, Z.A., Burnett, R.T. (2020) Fine particulate air pollution and human mortality: 25+ years of cohort studies. Environmental Research, 183, 108924.
46. Pöschl, U. (2005) Atmospheric aerosols: Composition, transformation, climate and health effects. Angewandte Chemie, 44(46), 7520-7540.
47. Puthussery, J.V., Singh, A., Rai, P., Bhattu, D., Kumar, V., Vats, P., Furger, M., Rastogi, N., Slowik, J.G., Ganguly, D., Prevot, A.S.H., Tripathi, S.N., Verma, V. (2020) Real-Time Measurements of PM2.5Oxidative Potential Using a Dithiothreitol Assay in Delhi, India. Environmental Science & Technology Letters, 7(7), 504-510.
48. Rahman, Q., Norwood, J., Hatch, G. (1997) Evidence that exposure of particulate air pollutants to human and rat alveolar macrophages leads to differential oxidative response. Biochemical and Biophysical Research Communications, 240(3), 669-672.
49. Rana, J., Uddin, J., Peltier, R., Oulhote, Y. (2019) Associations between indoor air pollution and acute respiratory infections among under-five children in afghanistan: Do SES and sex matter? International Journal of Environmental Research and Public Health, 16(16), 2910.
50. Rao, L., Zhang, L., Wang, X., Xie, T., Zhou, S., Lu, S. (2020) Oxidative Potential Induced by Ambient Particulate Matters with Acellular Assays: A Review. Processes, 8(11), 1410.
51. Rastogi, N., Patel, A. (2017) Oxidative potential of ambient aerosols: an Indian perspective. Current Science, 112(1), 35-39.
52. Roy, R., Jan, R., Yadav, S., Vasave, M.H., Gursumeeran Satsangi, P. (2015) Study of metals in radical-mediated toxicity of particulate matter in indoor environments of Pune, India. Air Quality, Atmosphere & Health, 9, 669–680.
53. Sambandam, B., Devasena, T., Hairul Islam, V.I., Prakhya, B.M. (2015) Characterization of coal fly ash nanoparticles and their induced in vitro cellular toxicity and oxidative DNA damage in different cell lines. Indian Journal of Experimental Biology, 53 (9), 585–593.
54. Seinfeld, J.H., Pandis, S.N. (2006) Atmospheric Chemistry and Physics: From Air Pollution to Climate Change (2nd Ed.). A wiley-interscience publication. JOHN WILEY & SONS, INC., pp. 1-1225.
55. Shafer, M.M., Perkins, D.A., Antkiewicz, D.S., Stone, E.A., Quraishi, T.A., Schauer, J.J. (2010) Reactive oxygen species activity and chemical speciation of size-fractionated atmospheric particulate matter from Lahore, Pakistan: An important role for transition metals. Journal of Environmental Monitoring, 12(3), 704-715.
56. Shahpoury, P., Harner, T., Lammel, G., Lelieveld, S., Tong, H., Wilson, J. (2019) Development of an antioxidant assay to study oxidative potential of airborne particulate matter. Atmospheric Measurement Techniques, 12, 6529-6539, 2019.
57. Shen, H., Anastasio, C. (2011) Formation of hydroxyl radical from San Joaquin Valley particles extracted in a cell-free surrogate lung fluid. Atmospheric Chemistry and Physics, 11(18), 9671-9682.
58. Singh, V., Singh, S., Biswal, A. (2021) Exceedances and trends of particulate matter (PM2.5) in five Indian megacities. The Science of the Total Environment, 750, 141461.
59. Steenhof, M., Gosens, I., Strak, M., Godri, K.J., Hoek, G., Cassee, F.R., Mudway, I.S., Kelly, F.J., Harrison, R.M., Lebret, E., Brunekreef, B., Janssen, N.A.H., Pieters, R.H.H. (2011) In vitro toxicity of particulate matter (PM) collected at different sites in the Netherlands is associated with PM composition, size fraction and oxidative potential - the RAPTES project. Particle and Fibre Toxicology, 8(26), 1-15.
60. Subramanian, A. (2019) Validating India’s GDP Growth Estimates. CID Faculty Working Paper No. 357. Working Papers, Center for International Development at Harvard University
61. Sughis, M., Nawrot, T.S., Ihsan-ul-haque, S., Amjad, A., Nemery, B. (2012) Blood pressure and particulate air pollution in schoolchildren of Lahore, Pakistan. BMC Public Health, 12, 378.
62. Terzano, C., Stefano, D.I., Conti, V., Graziani, E., Petroianni, A. (2010) Air pollution ultrafine particles: toxicity beyond the lung. European Review for Medical and Pharmacological Sciences, 14(10), 809-821. PMID: 21222367.
63. Turrens, J.F. (2003) Mitochondrial formation of reactive oxygen species. The Journal of Physiology, 552(Pt 2), 335-344.
64. Valavanidis, A., Fiotakis, K., Vlachogianni, T. (2008) Airborne particulate matter and human health: Toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. Journal of Environmental Science and Health, Part C: Environmental Carcinogenesis and Ecotoxicology Reviews, 26(4), 339- 362.
65. Venkatachari, P., Hopke, P.K., Grover, B.D., Eatough, D.J. (2005) Measurement of particle-bound reactive oxygen species in rubidoux aerosols. Journal of Atmospheric Chemistry, 50, 49-58.
66. Verma, V., Wang, Y., El-Afifi, R., Fang, T., Rowland, J., Russell, A.G., Weber, R.J. (2015) Fractionating ambient humic-like substances (HULIS) for their reactive oxygen species activity - Assessing the importance of quinones and atmospheric aging. Atmospheric Environment, 120, 351-359.
67. Vreeland, H., Schauer, J.J., Russell, A.G., Marshall, J.D., Fushimi, A., Jain, G., Sethuraman, K., Verma, V., Tripathi, S.N., Bergin, M.H. (2016) Chemical characterization and toxicity of particulate matter emissions from roadside trash combustion in urban India. Atmospheric Environment, 147, 22-30.
68. Wardman, P. (2007) Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects. Free Radical Biology and Medicine, 43(7), 995-1022.
69. WHO (2016) Ambient Air Pollution: A Global Assessment of Exposure and Burden of Disease. World Health Organization, pp. 1-131.
70. Xiao, W., Wang, R.S., Handy, D.E., Loscalzo, J. (2018) NAD (H) and NADP (H) Redox Couples and Cellular Energy Metabolism. Antioxidants & Redox Signaling, 28(3), 251- 272.
71. Yadav, S., Vernekar, P., Kapoor, T.S., Venkataraman, C., Phuleria, H.C. (2019) Chemical Characterisation and Oxidative Potential of Aerosols Emitted From Solid Biomass Fuels Use in Rural India. American Geophysical Union, Fall Meeting 2019, abstract #A23L-2970.
72. Yamamoto, S.S., Phalkey, R., Malik, A.A. (2014) A systematic review of air pollution as a risk factor for cardiovascular disease in South Asia: Limited evidence from India and Pakistan. International Journal of Hygiene and Environmental Health, 217(2-3), 133-144.
73. Yang, A., Janssen, N.A.H., Brunekreef, B., Cassee, F.R., Hoek, G., Gehring, U. (2016) Children’s respiratory health and oxidative potential of PM2.5: The PIAMA birth cohort study. Occupational and Environmental Medicine, 73(3), 154- 160.
74. Yang, A., Jedynska, A., Hellack, B., Kooter, I., Hoek, G., Brunekreef, B., Kuhlbusch, T.A.J., Cassee, F.R., Janssen, N.A.H. (2014) Measurement of the oxidative potential of PM2.5 and its constituents: The effect of extraction solvent and filter type. Atmospheric Environment, 83, 35-42.
75. Yu, H., Wei, J., Cheng, Y., Subedi, K., Verma, V. (2018) Synergistic and antagonistic interactions among the particulate matter components in generating reactive oxygen species based on the dithiothreitol assay. Environmental Science & Technology, 52(4), 2261-2270.