Air pollution we breathe: Assessing the air quality and human health impact in a megacity of Southeast Asia.

With 24 million inhabitants and 6.6 million vehicles on the roads, Karachi, Pakistan ranks among the world's most polluted cities due to high levels of fine particulate matter (PM2.5). This study aims to investigate PM2.5 mass, seasonal and temporal variability, chemical characterization, source apportionment, and health risk assessment at two urban sites in Karachi. Samples were analyzed using ion chromatography and dual-wavelength optical transmissometer for various inorganic components (anions, cations, and trace elements) and black carbon (BC). Several PM2.5 pollution episodes were frequently observed, with annual mean concentrations at Kemari (140 ± 179 µg/m3) and Malir (95 ± 40.9 µg/m3) being significantly above the World Health Organization's guidelines of 5 µg/m3. Chemical composition at both sites exhibited seasonal variability, with higher pollution levels in winter and fall and lower concentrations in summer. The annual average BC concentrations were 4.86 ± 5.29 µg/m3 and 4.52 ± 3.68 µg/m3, respectively. A Positive Matrix Factorization (PMF) analysis identified 5 factors, crustal, sea salt, vehicular exhaust, fossil-fuel combustion, and industrial emission. The health risk assessment indicated a higher number of deaths in colder seasons (fall and winter) at the Kemari (328,794 and 287,814) and Malir (228,406 and 165,737) sites and potential non-carcinogenic and carcinogenic risks to children from metals. The non-carcinogenic risk of PM2.5 bound Pb, Fe, Zn, Mn, Cr, Cu and Ni via inhalation exposure were within the acceptable level (<1) for adults. However, potential non-carcinogenic and carcinogenic health risk posed by Pb and Cr through inhalation were observed for children. The findings exhibit critical levels of air pollution that exceed the safe limits in Karachi, posing significant health risks to children and sensitive groups. Our study underscores the urgent need for effective emission control strategies and policy interventions to mitigate these air pollution risks.

Fine particulate matter and its chemical constituents' levels: A troubling environmental and human health situation in Karachi, Pakistan.

Like many urban centers in developing countries, the effect of air pollution in Karachi is understudied. The goal of this study was to determine the chemical characterization, temporal and seasonal variability, sources, and health impacts of fine particulate matter (PM2.5) in Karachi, Pakistan. Daily samples of PM2.5 were collected using a low-volume air sampler at two different sites (Makro and Karachi University) over the four seasons between October 2009 and August 2010. Samples were analyzed for black carbon (BC), trace metals, and water-soluble ions. Results showed that the annual average concentrations of PM2.5 at Makro and Karachi University were 114 ± 115 and 71.7 ± 56.4 µg m-3, respectively, about 22.8 and 14.3-fold higher than the World Health Organization annual guideline of 5 µg m-3. BC concentrations were 3.39 ± 1.97 and 2.70 ± 2.06 µg m-3, respectively. The concentrations of PM2.5, BC, trace metals, and ions at the two sites showed clear seasonal trends, with higher concentrations in winter and lower concentrations in summer. The trace metals and ionic species with the highest concentrations were Pb, S, Zn, Ca, Si, Cl, Fe, and SO42-. The air quality index in the fall and winter at both sites was about 68 %, which is "unhealthy" for the general population. Positive Matrix Factorization revealed the overall contribution to PM2.5 at the Makro site came from three major sources - industrial emissions (13.3 %), vehicular emissions (59.1 %), and oil combustion (23.3 %). The estimates of expected number of deaths due to short-term exposure to PM2.5 were high in the fall and winter at both sites, with an annual mean estimate of 3592 expected number of deaths at the Makro site. Attention should be paid to the reduction of inorganic pollutants from industrial facilities, vehicular traffic, and fossil fuel combustion, due to their extremely high contribution to PM2.5 mass and health risks.

State of gaseous air pollutants and resulting health effects in Karachi, Pakistan.

Karachi, Pakistan, is a priority site for air pollution research due to high emissions of air pollutants from vehicular traffic, industrial activities, and biomass burning, as well as rapid growth in population. The objectives of this study were to investigate the levels of gaseous pollutants (NO, NO2, O3, HNO3, and SO2) in Karachi, to determine temporal and seasonal variations, to compare Karachi's air quality with other urban centers, to identify relationships with meteorological conditions, to identify source characterization, and to perform a backward-in-time trajectory analysis and a health impact assessment. Daily samples of gaseous pollutants were collected for six consecutive weeks in each of the four seasons for a year. Daily maximum concentrations of NO (90 parts per billion by volume (ppbv)), NO2 (28.1 ppbv), O3 (57.8 ppbv), and SO2 (331 ppbv) were recorded in fall, while HNO3 (9129 parts per trillion by volume (pptv)) was recorded in spring. Seasonal average concentrations were high in winter for NO (9.47 ± 7.82 ppbv), NO2 (4.84 ± 3.35 ppbv), and O3 (8.92 ± 7.65 ppbv), while HNO3 (629 ± 1316 pptv) and SO2 (20.2 ± 39.4 ppbv) were high in spring and fall, respectively. The observed SO2 seasonal average concentration in fall (20.2 ± 39.4) was 5 times higher than that in summer (3.97 ± 2.77) with the fall 24-h average (120 ppbv) exceeding the WHO daily guideline (7.64 ppbv) by a factor of about 15.7. A health impact assessment estimated an increase of 1200 and 569 deaths due to short-term exposure to SO2 in fall and spring, respectively. Chronic daily intake estimated risk per 1000 was 0.99, 0.47, 0.45, and 0.26 for SO2 in fall, NO in winter, O3 in winter, and NO2 in spring, respectively. This study confirms the effect of poor urban air quality on public health and demonstrated the influence of photochemical reactions as well as unfavorable meteorological conditions on the formation of secondary pollutants.

Assessing the association between fine particulate matter (PM2.5) constituents and cardiovascular diseases in a mega-city of Pakistan.

Concerning PM2.5 concentrations, rapid industrialization, along with increase in cardiovascular disease (CVD) were recorded in Pakistan, especially in urban areas. The degree to which air pollution contributes to the increase in the burden of CVD in Pakistan has not been assessed due to lack of data. This study aims to describe the characteristics of PM2.5 constituents and investigate the impact of individual PM2.5 constituent on cardiovascular morbidity in Karachi, a mega city in Pakistan. Daily levels of twenty-one constituents of PM2.5 were analyzed using samples collected at two sites from fall 2008 to summer 2009 in Karachi. Hospital admission and emergency room visits due to CVD were collected from two large hospitals. Negative Binominal Regression was used to estimate associations between pollutants and the risk of CVD. All PM2.5 constituents were assessed in single-pollutant models and selected constituents were assessed in multi-pollutant models adjusting for PM2.5 mass and gaseous pollutants. The most common CVD subtypes among our participants were ischemic heart disease, hypertension, heart failure, and cardiomyopathy. Extremely high levels of PM2.5 constituents from fossil-fuels combustion and industrial emissions were observed, with notable peaks in winter. The most consistent associations were found between exposure to nickel (5-14% increase per interquartile range) and cardiovascular hospital admissions. Suggestive evidence was also observed for associations between cardiovascular hospital admissions and Al, Fe, Ti, and nitrate. Our findings suggested that PM2.5 generated from fossil-fuels combustion and road dust resuspension were associated with the increased risk of CVD in Pakistan.

Ambient air quality in the holy city of Makkah: A source apportionment with elemental enrichment factors (EFs) and factor analysis (PMF).

Air pollution remains a major global public health and environmental issue. We assessed the levels of PM2.5 and delineated the major sources in Makkah, Saudi Arabia. Fine particulate matter (PM2.5) sampling was performed from February 26, 2014-January 27, 2015 in four cycles/seasons. Samples were analyzed for black carbon (BC) and trace elements (TEs). PM2.5 source apportionment was performed by computing enrichment factors (EFs) and positive matrix factorization (PMF). Backward-in time trajectories were used to assess the long-range transport. Significant seasonal variations in PM2.5 were observed, Spring: 113 ±â€¯67.1, Summer: 88.3 ±â€¯36.4, Fall: 67.8 ±â€¯24, and Winter: 67.6 ±â€¯36.9 µg m-3. The 24-h PM2.5 exceeded the WHO (25 µg m-3) and Saudi Arabia's (35 µg m-3) guidelines, with an air quality index (AQI) of "unhealthy to hazardous" to human health. Most delta-C computations were below zero, indicating minor contributions from bio-mass burning. TEs were primarily Si, Ca, Fe, Al, S, K and Mg, suggesting major contributions from soil (Si, Ca, Fe, Al, Mg), and industrial and vehicular emissions (S, Ca, Al, Fe, K). EF defined two broad categories of TEs as: anthropogenic (Cu, Zn, Eu, Cl, Pb, S, Br and Lu), and earth-crust derived (Al, Si, Na, Mg, Rb, K, Zr, Ti, Fe, Mn, Sr, Y, Cr, Ga, Ca, Ni and Ce). Notably, all the anthropogenic TEs can be linked to industrial and vehicular emissions. PMF analysis defined four major sources as: vehicular emissions, 30.1%; industrial-mixed dust, 28.9%; soil/earth-crust, 24.7%; and fossil-fuels/oil combustion, 16.3%. Plots of wind trajectories indicated wind direction and regional transport as major influences on air pollution levels in Makkah. In collusion, anthropogenic emissions contributed >75% of the observed air pollution in Makkah. Developing strategies for reducing anthropogenic emissions are paramount to controlling particulate air pollution in this region.

Association of fine particulate air pollution with cardiopulmonary morbidity in Western Coast of Saudi Arabia.

OBJECTIVES: To assess cardiopulmonary morbidity associated with daily exposures to PM2.5 in Western Coast of Saudi Arabia. Methods: We monitored 24-h PM2.5 and its constituents including black carbon (BC), particulate sulfate (p-SO42-), nitrate (p-NO3-), ammonium (p-NH4+) and trace elements (TEs) at a site in Rabigh, Saudi Arabia from May to June 2013 with simultaneous collection of hospital data (N=2513). Cardiopulmonary morbidity risk was determined in a generalized linear time-series model.  Results: Exposure to PM2.5 was associated with a 7.6% (p=0.056) increase in risk of respiratory disease (RD) in females. Black carbon increased RD morbidity risk by 68.1% (p=0.056) in females. Exposure to p-SO42- increased the cardiovascular disease (CVD) risk by up to 5.3% (p=0.048) in males; and RD by 2.9% (p=0.037) in females and 2.5% (p=0.022) in males. The p-NH4+ increased CVD risk by up to 20.3% (p=0.033) in males; and RD by 10.7% (p=0.014) in females and 8% (p=0.031) in males. No statistically significant association was observed for p-NO3- and TEs exposure. Conclusion: Overall, results show an increased risk for cardiopulmonary morbidity following exposure to air pollution.

Multipathways human health risk assessment of trihalomethane exposure through drinking water.

Life-time human health risk of cancer attributed to trihalomethanes in drinking water in an urban-industrialized area of Karachi (Pakistan) was conducted through multiple pathways of exposure. The extent of cancer risk was compared with USEPA guidelines. Human health cancer risk for total trihalomethanes (TTHMs) through ingestion and dermal routes were estimated in "acceptable-low risk" (≥1.0E-06; ≤5.10E-05), whereas through inhalation route it was estimated under "acceptable-high risk" (≥5.10E-05; ≤1.0E-04) category. However, at some industrial-urban areas cancer risk for CHCl3 were estimated under "unacceptable risk" (≥1.0E-04) through inhalation route.

Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: roles of PAH interactions and PAH metabolites.

The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 microM benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17beta-estradiol (E(2)) metabolism, whereas BKF levels greater than 1 muM inhibited E(2) metabolism. Time course studies showed that induction of CYP1-catalyzed E(2) metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays to induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity.

Transient induction of cytochromes P450 1A1 and 1B1 in MCF-7 human breast cancer cells by indirubin.

The aryl hydrocarbon receptor (AhR), when activated by exogenous ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), regulates expression of several phase I and phase II enzymes and is also involved in the regulation of cell proliferation. Several studies suggest that endogenous AhR ligand(s) may exist. One putative endogenous ligand is indirubin, which was recently identified in human urine and bovine serum. We determined the effect of indirubin in MCF-7 breast cancer cells on induction of the activities of cytochromes P450 (CYP) 1A1 and 1B1, as measured by estradiol and ethoxyresorufin metabolism, and on induction of the CYP1A1 and CYP1B1 mRNAs. With 4-hr exposure, the effects of indirubin and TCDD at 10nM on CYP activity were comparable, but the effects of indirubin, unlike those of TCDD, were transitory. Indirubin-induced ethoxyresorufin-O-deethylase activity was maximal by 6-9 hr post-exposure and had disappeared by 24 hr, whereas TCDD-induced activities remained elevated for at least 72 hr. The effects of indirubin on CYP mRNA induction were maximal at 3 hr. Indirubin was metabolized by microsomes containing cDNA-expressed human CYP1A1 or CYP1B1. The potency of indirubin was comparable to that of TCDD in a CYP1B1-promoter-driven luciferase assay, when MCF-7 cells were co-exposed to the AhR ligands together with the CYP inhibitor, ellipticine. Thus, if indirubin is an endogenous AhR ligand, then AhR-mediated signaling by indirubin is likely to be transient and tightly controlled by the ability of indirubin to induce CYP1A1 and CYP1B1, and hence its own metabolism.

Estrogen regulates Ah responsiveness in MCF-7 breast cancer cells.

Cytochrome P450 (CYP)1A1 and CYP1B1, which are under the regulatory control of the aryl hydrocarbon (Ah) receptor (AhR), catalyze the metabolic activation of numerous procarcinogens and the hydroxylation of 17beta-estradiol (E2) at the C-2 and C-4 positions, respectively. There is evidence of cross-talk between estrogen receptor alpha (ERalpha)- and AhR-mediated signaling in breast and endometrial cells. To further examine these interactions, we investigated the short- and long-term effects of E2 exposure on Ah responsiveness in MCF-7 human breast cancer cells. Short-term exposure to 1 nM E2 elevated the ratio of the 4- to 2-hydroxylation pathways of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced E2 metabolism and the ratio of the induced CYP1B1 to CYP1A1 mRNA levels, as determined by real-time PCR. Cells maintained long-term (9-12 months) in low-E2 medium progressively lost Ah responsiveness, as indicated by diminished rates of TCDD-induced E2 metabolism and ethoxyresorufin O-deethylase activity, and the reduced expression of the CYP1A1 and CYP1B1 mRNAs and proteins levels. These E2-deprived cells showed elevated levels of ERalpha mRNA, depressed levels of AhR mRNA, and unchanged levels of the AhR nuclear translocator mRNA. Transient transfection studies using a CYP1B1-promoter-luciferase reporter construct showed that reduced CYP1B1 promoter activity in E2-deprived cells could be restored by co-transfection with an AhR expression construct, indicating that AhR expression was limiting in these cells. The reduced Ah responsiveness of E2-deprived cells was reversed by culture for four passages in medium supplemented with 1 nM E2; ERalpha and AhR mRNAs returned to near-normal levels and the inducibility of the CYP1A1 and CYP1B1 mRNAs, proteins, and E2 metabolic activities by TCDD was restored. These studies indicate that the continued presence of estrogen is required to maintain high levels of AhR expression and inducibility of the procarcinogen-bioactivating enzymes, CYP1A1 and CYP1B1, in MCF-7 cells.

Stimulatory effect of cigarette smoking on the 15 alpha-hydroxylation of estradiol by human term placenta.

OBJECTIVE: Our objective was to characterize the oxidative metabolism of estradiol by human term placenta and its modulation by cigarette smoking. METHODS: Placental microsomes were prepared from term placentas obtained from 13 cigarette smokers (20 to 30 cigarettes per day until the time of delivery) and 13 control subjects who were nonsmokers. Estrogen metabolism was studied by incubation of 250 nmol/L [(3)H]estradiol with placental microsomes and NADPH, and the estrogen metabolites were determined by HPLC and gas chromatography-mass spectrometry. RESULTS: 2-Hydroxyestradiol was the major hydroxyestrogen detected, followed by 6alpha-hydroxyestradiol. Small amounts of several other hydroxyestrogen metabolites (4-hydroxyestradiol, 6beta-hydroxyestradiol, 7alpha-hydroxyestradiol, and 16alpha-hydroxyestradiol) were also detected. Large amounts of estrone plus small amounts of 2-hydroxyestrone and unidentified nonpolar metabolites were formed. Cigarette smoking stimulated the placental hydroxylation of benzo[a ]pyrene by about 16-fold. Cigarette smoking had little or no effect on the overall rate of placental estradiol metabolism or on the formation of estrone, 2-hydroxyestradiol, 2-hydroxyestrone, or 16alpha-hydroxyestradiol. However, placental formation of 4-hydroxyestradiol and 7alpha-hydroxyestradiol was increased 38% (P =.08) and 150% (P =.05), respectively, in cigarette smokers. The formation of 6alpha-hydroxyestradiol was decreased 33% (P =.04). Metabolic formation of 15alpha-hydroxyestradiol was observed during incubations of estradiol with placental microsomes from 11 of the 13 cigarette smokers, but this metabolite was not detected during incubations with placental microsomes from any of the 13 nonsmokers. Analysis of data from all 26 placentas showed that the 15alpha-hydroxylation of estradiol was highly correlated with benzo[a ]pyrene hydroxylation (r = 0.93; P <.001). CONCLUSIONS: Many hydroxylated estradiol metabolites were formed by placental microsomes from cigarette smokers and nonsmokers. 15alpha-Hydroxylation of estradiol was markedly stimulated in the placentas of cigarette smokers.

Induction of CYP1A1 and CYP1B1 in T-47D human breast cancer cells by benzo[a]pyrene is diminished by arsenite.

Polycyclic aromatic hydrocarbons (PAHs) and metals are often environmental cocontaminants, yet there have been relatively few studies of combined effects of PAHs and metals on cytochrome P450 (P450)-catalyzed metabolism. We examined the effects of NaAsO(2) in combination with benzo[a]pyrene (BAP) on CYP1A1 and CYP1B1 in T-47D human breast cancer cells by using estrogen metabolism as a probe of their activities. Exposure to BAP caused elevated rates of the 2- and 4-hydroxylation pathways of estrogen metabolism, indicating induction of both CYP1A1, an estradiol 2-hydroxylase, and CYP1B1, an estradiol 4-hydroxylase. BAP-induced metabolism peaked 9 to 16 h after exposure and returned to near-basal levels by 48 h. Concentration-response studies showed maximal induction of the 2- and 4-hydroxylation pathways at 3 microM BAP; higher levels caused reduced rates of metabolism due to inhibition of CYP1A1 and CYP1B1. NaAsO(2) caused pronounced decreases in the induction of CYP1A1 and CYP1B1 by 3 microM BAP because cotreatment with 10 microM NaAsO(2) inhibited the rates of the 2- and 4-hydroxylation pathways by 86 and 92%, respectively. Western immunoblots showed diminished levels of BAP-induced CYP1A1 by coexposure to NaAsO(2). The levels of the CYP1A1 and CYP1B1 mRNAs induced by BAP were not significantly affected by coexposure to NaAsO(2); however, heme oxygenase 1 mRNA levels were markedly induced by coexposure to BAP and NaAsO(2). These results indicate a post-transcriptional inhibitory effect of arsenite on the expression of CYP1A1 and CYP1B1 in T-47D cells, possibly resulting from reduced heme availability.