The Concentration of BTEX in the Air of Tehran: A Systematic Review-Meta Analysis and Risk Assessment

In the current study, the concentration of some pollutants which are categorized as volatile organic compounds (VOCs), including benzene (B), toluene (T), ethylbenzene (E), and o-xylenes (o-X), in the air of Tehran was evaluated by the aid of a systematic review and meta-analysis approach. Also, the health risk for the exposed population was estimated using the recommended methods by the Environmental Protection Agency (EPA). The rank order based on their concentration in BTEX was benzene (149.18 µg/m3: 31%) > o-xylene (127.16 µg/m3: 27%) > ethylbenzene (110.15 µg/m3: 23%) > toluene (87.97 µg/m3: 19%). The ratio B/T in this study was calculated as 1.69, repressing that both stationary and mobile sources of emission can be considered as the main sources for benzene and toluene. Moreover, strong photochemical activity in Tehran was demonstrated by the high ratio of E/o-X. Meta-regression indicates that the concentration of BTEX has insignificantly (p-value > 0.05) increased over time. The BTEX compounds based on the target hazard quotient (THQ) were ordered as benzene > o-xylene > ethylbenzene > toluene. Percentile 95% of THQ due to benzene (4.973) and o-xylene (1.272) was higher than a value of 1. Percentile 95% excessive cancer risk (ECR) for benzene (1.25 × 106) and ethylbenzene (1.11 × 106) was higher than a value of 1.00 × 106. The health risk assessment indicated that the population of Tehran are at considerable non-carcinogenic and carcinogenic risks.


Introduction
The air quality in urban areas depends on different factors such as atmospheric dispersion conditions, solar radiation, meteorological factors, geographical factors, deposition, and pollutant emissions [1]. In the last few decades, with increases in urbanization and developments in human life, the issue of air pollution has attracted considerable attention [2,3]. The primary sources of air pollution in urban regions can be summarized as natural and anthropogenic sources [4,5]. In this context, air pollutants such as volatile organic compounds (VOCs), sulfur oxides (SOx), ozone (O 3 ), carbon oxides (COs), particulate matter (PM), nitrogen oxides (NOx), and radioactive pollutants are released from these sources [5,6].
The main sources of VOCs are anthropogenic and biogenic sources [7], including incomplete combustion in motor vehicles (fossil fuels), the petrochemical process, the fabrication of rubber and resin, solvents, and paint industries [8,9]. The presence of VOCs in a variety of forms such as toluene, benzene, ethylbenzene, and meta (m), para (p), and ortho(o) xylene in the indoor or outdoor air is important issue due to the consequence of non-carcinogenic risks (e.g., neurological impairment, allergy, nose and eye irritation, kidney and liver dysfunction, and heart disease) [10][11][12] and carcinogenic risks (e.g., lung cancer and leukemia) [13][14][15][16].
Among VOCs, benzene, as a hazardous compound with a relatively long lifetime, belongs to group 1; carcinogenic to humans [17,18]. Whilst the mutagenicity and carcinogenicity of toluene, ethylbenzene, and xylenes have not been proven [19,20], they are precursors of toxic radical in the atmosphere [21]. In this regard, in addition to direct adverse health effects of BTEX, they can be classified as the main precursors of the production of secondary pollutants by photochemical reactions such as proxy acetyl nitrate (PAN) and O 3, which can endanger human health [4,[22][23][24][25][26][27].
Several investigations have been performed regarding measuring the concentration of ambient BTEX around the world and also to assess the quality and quantity of air pollutants and their effects on human health [24,[28][29][30][31][32][33][34]. In this regard, useful information considering ratios used for determining photochemical activity in the atmosphere, as well as the sources of substances such as benzene/toluene (B/T) and ethylbenzene/m, p-xylene (E/X), were provided [8].
Although Tehran, with more than nine million permanent people and three million floating people, was designed for more than 750,000 motor vehicles, more than four million motor vehicles are moving in this metropolitan [35]. Besides, several factories are located in southern Tehran, with the emission of various pollutants into the ambient air [36]. Despite a high number of conducted studies regarding the concentration and numerous emission sources for BTEX in Tehran ambient air [37][38][39][40][41][42][43], no systematic review and meta-analysis study has been conducted to assess the related health risks. Therefore, for the first time, in the current study, the carcinogenesis and non-carcinogenesis risks of BTEX pollutants in Tehran will be assessed by using a systematic review and meta-analysis approach.

Strategy of Search
The search strategy was performed to obtain all citations regarding the concentration of BTEX in the air of Tehran between 2005 to 2018. The systematic review was conducted based on the Cochrane method [44] ((keyword (benzene) or keyword (toluene) or keyword (ethylbenzene) or keyword (xylene) or keyword (BTEX) or keyword (volatile and organic and compound))) and ((keyword (air and pollution) or keyword (ambient and air) or keyword (outdoor and air))) and (keyword (Iran)); Embase: 'benzene':ab,ti OR 'toluene':ab,ti OR 'ethylbenzene':ab,ti OR 'xylene':ab,ti OR 'btex':ab,ti OR 'volatile organic compound':ab,ti AND 'air pollution'/exp OR 'air pollution' OR 'ambient air':ab,ti OR 'outdoor air'/exp OR 'outdoor air' AND 'IRAN':ab,ti. Thirteen years (1 January 2005 and 11 June 2018) was selected as the period of investigation.

Screening of Articles
The evaluation of initially retrieved articles was performed independently according to (1) title, (2) abstract, and (3) full-text of the articles [45,46]. According to the title and abstract, some articles that did not perform investigations on the concentration of BTEX in the air of Tehran were excluded.
The full text of the obtained papers was downloaded, after the abstract screening. Criteria for including articles were: (1) descriptive study on the contamination of BTEX; (2) full text available; (3) original studies; and (4) reporting of the concentration of BTEX in ambient air in Tehran. Disagreement among two of the authors was resolved by discussion; otherwise, a third author decided. A reference list of retrieved articles was also checked to obtain more articles. The required management of obtained references was carried out using EndNote X7 ® (Thomson Reuters, Toronto, Canada) software [46].

Data Extraction and Definitions
The collected data from each article can be summarized as sampling date, type of monitoring station, number of monitoring stations, sample size, the concentration of BTEX, the method of detection, the limit of detection, and the limit of quantitation (Table 1). BTEX represents volatile chemicals including benzene, toluene, ethylbenzene, and xylene that are emitted from crude oil, natural gas, and petroleum deposits [47]. In this regard, because of the majority of studies performed on O-xylene, it was extracted from obtained articles.

Meta-Analysis
While the heterogeneity was higher than 50%, the random effect model (REM) was used to estimate the pooled concentration of BTEX in ambient air [45,48].
The standard error (SE) of the concentration of BTEX was calculated using standard deviation and sample size (SE = SD/ √ n) [45]. According to the mean and standard error, the pooled concentration of BTEX was estimated [49,50]. All data were analyzed using STATA 14.0 statistical software (College Station, TX, USA). p-value < 0.05 was considered statistically significant.

Non-Carcinogenic Risk
In the current study, according to part A and B of the risk assessment manual of EPA, the exposure dose to BTEX in ambient air was estimated [51]. Dose exposure via the inhalation [exposure concentration (EC)] pathway was calculated by Equation (1) [52,53]. All parameters used in this equation are presented in Table 2.  [55] 1000 Convert factor mg to µg -- The conversion of the concentration from ppb to µg/m 3 for benzene, toluene, ethylbenzene, and o-xylene was performed using 3.243, 0.843, 19.45, and 4.33 convert coefficients, respectively [59].
To estimate the non-carcinogenic risk of BTEX in the ambient air, the target hazard quotient (THQ) was calculated using Equation (2) [51]: The total target hazard quotient (TTHQ) is equal to the sum of individual THQ [60][61][62][63][64][65][66]. The TTHQ of BTEX was calculated by Equation (3): When THQ and/or TTHQ is lower than or equal to a value of 1, the population are not at a significant non-carcinogenic risk [17].

Carcinogenic Risk
The carcinogenic risk of benzene and ethylbenzene in adults and children was estimated using Equation (4): The related parameters of Equations (1)-(4) are shown in Table 2.
When the ECR value of benzene and ethylbenzene is lower than 1.00 × 10 6 , between 1.00 × 10 6 to 1.00 × 10 4 , and higher than 1.00 × 10 4 , the exposed population are at no considerable, threshold, and considerable cancer risk, respectively [54]. In the current study, the cut off point for endangering the population was a percentile of 95% (worse scenario) of THQ and ECR [65].

The Process of Select Papers
Among the 230 papers obtained published from 2005 to 2018 from all databases including PubMed (n = 83), Scopus (n = 66), Embased (n = 53), and SID (n = 28) in the identification step, 121 papers were excluded due to duplication. After the assessment of titles, 48 papers were regarded as unsuitable. The abstracts of 61 papers were checked, and 23 papers were excluded. Then, the full texts of the 38 papers were reviewed and finally, seven papers with 1678 samples were included in the current study ( Figure 1).
The related parameters of Equations (1)-(4) are shown in Table 2.
When the ECR value of benzene and ethylbenzene is lower than 1.00 × 10 6 , between 1.00 × 10 6 to 1.00 × 10 4 , and higher than 1.00 × 10 4 , the exposed population are at no considerable, threshold, and considerable cancer risk, respectively [54]. In the current study, the cut off point for endangering the population was a percentile of 95% (worse scenario) of THQ and ECR [65].

The Process of Select Papers
Among the 230 papers obtained published from 2005 to 2018 from all databases including PubMed (n = 83), Scopus (n = 66), Embased (n = 53), and SID (n = 28) in the identification step, 121 papers were excluded due to duplication. After the assessment of titles, 48 papers were regarded as unsuitable. The abstracts of 61 papers were checked, and 23 papers were excluded. Then, the full texts of the 38 papers were reviewed and finally, seven papers with 1678 samples were included in the current study (Figure 1).

Concentration of BTEX
The pooled concentration (ppb) of benzene, toluene, ethylbenzene, and o-xylenes, is demonstrated in Figure 2a   A comparison of the concentration of BTEX in Tehran with other urban areas in the world is presented in Table 3. According to our findings, the pooled concentrations of benzene (149.18 µg/m 3 ) and o-xylene (125.57 µg/m 3 ) in Tehran were higher than those in other cities around the world (Table 3)   and o-xylene (125.57 µg/m 3 ) in Tehran were higher than those in other cities around the world (Table 3) [6,33,[67][68][69][70][71][72][73][74] (Table 3).
The concentration of BTEX in ambient air of Tehran was higher than many urban regions in the world ( Table 3). The inversion phenomenon was mentioned as one of the leading causes of the high concentration of BTEX in Tehran [37,38,40,42]. It occurs in the cold seasons that cause ambient air pollutants such as VOCs to become trapped in the surface layer of the Earth, which can result in intensifying air pollution levels [37].
In addition to the inversion phenomenon, fossil fuel consumption of old vehicles, low-quality fuel, population congestion, non-standard streets, and highways, besides several factories in the south of Tehran such as iron and steel industries, are other reasons for the high level of BTEX in Tehran city [37,38,40,42].
The higher concentration of toluene and ethylbenzene in Malaysia (Kuala Lumpur) compared with Tehran is due to the higher evaporation of petrol vapors (gasoline evaporation) and emission of higher concentrations of toluene and ethylbenzene by motor vehicles [73].

The Ratio between BTEX Compounds
The ratios of benzene/toluene (B/T) and ethylbenzene/m, p-xylene (E/X) can be used to assess the photochemical activity in the atmosphere and sources [8,75]. The ratio between BTEX compounds is the main parameter for discovering the emission sources of BTEX in the outdoor air [76,77]. The calculated B/T ratio in the range of 0.23-0.66 shows that vehicles and traffic are the main emission sources of toluene and benzene in the ambient air of Tehran [8,75,78,79]. The B/T ratio lower than this range indicates that toluene and benzene mainly originated from stationary sources. Likewise, if the B/T ratio is higher than this range, stationary (factory) and mobile (Motorcycle and car) sources are the main sources of emission [8,75]. Ratios of benzene/toluene (B/T) and ethylbenzene/o-xylene (E/o-X) in Tehran and other areas are presented in Table 4.  The B/T ratio in this study was 1.69, which was higher than 0.23-0.66, representing that the primary sources of benzene and toluene could be both stationary and mobile sources of emission. Similar to our study, the B/T ratio in ambient air in France (Orleans) and China (Beijing) was higher than the B/T ratio in this study (0.66) [24,33,70,85]. The B/T ratio in ambient air of China (Hong Kong), France (Paris), South Korea (Seoul), Turkey (Kocaeli), and Spain (Navarra) [25,32,70,71,80] was lower than 0.23, indicating that toluene and benzene mainly originated from stationary sources [8,75].

Area Study B/T E/O-X References
The ratio of E/X is a good indicator that indicates the degree of photochemical reactions [86,87]. A higher ratio of E/X than Spain (Navarra: 0.82), Turkey (Kocaeli: 0.78), and Italy (Bari: 0.71) shows that photochemical activity in the ambient air of Tehran is stronger than in Spain, Turkey, and Italy (Table 4) [88].

Non-Carcinogenic Risk Assessment
Non-Carcinogenic Risk BTEX compounds are presented in Table 5. Percentile 95% of THQ of benzene, toluene, ethylbenzene, and o-xylene was determined as 5.342, 0.021, 0.142, and 1.522, respectively ( Table 5). The rank order of BTEX compounds based on THQ was benzene > o-xylene > ethylbenzene > toluene. THQ of benzene was higher than other VOC compounds because the concentration of benzene was the highest (Table 5), and also its RfC i was the lowest [55]. Percentile 95% of THQ of benzene and o-xylene was higher than the value of 1. Also, TTHQ values based on mean and percentile 95% was 6.37 and 7.07, respectively, which were higher than a value of 1 ( Figure 4). The health risk assessment shows that the residents of Tehran are at a considerable non-carcinogenic risk (THQ and TTHQ > 1 value). THQ values of benzene, toluene, ethylbenzene, and o-xylene in the China (Beijing) city were 3.2 × 10 2 , 3.37 × 10 4 , 3.19 × 10 4 , and 1.5 × 10 3 , respectively [70], which were lower than Tehran city. The lower concentration of BTEX in ambient air of China (Beijing) city ( Non-Carcinogenic Risk BTEX compounds are presented in Table 5. Percentile 95% of THQ of benzene, toluene, ethylbenzene, and o-xylene was determined as 5.342, 0.021, 0.142, and 1.522, respectively ( Table 5). The rank order of BTEX compounds based on THQ was benzene > o-xylene > ethylbenzene > toluene. THQ of benzene was higher than other VOC compounds because the concentration of benzene was the highest (Table 5), and also its RfCi was the lowest [55].
Percentile 95% of THQ of benzene and o-xylene was higher than the value of 1. Also, TTHQ values based on mean and percentile 95% was 6.37 and 7.07, respectively, which were higher than a value of 1 ( Figure 4). The health risk assessment shows that the residents of Tehran are at a considerable non-carcinogenic risk (THQ and TTHQ > 1 value). THQ values of benzene, toluene, ethylbenzene, and o-xylene in the China (Beijing) city were 3.2 × 10 2 , 3.37 × 10 4 , 3.19 × 10 4 , and 1.5 × 10 3 , respectively [70], which were lower than Tehran city. The lower concentration of BTEX in ambient air of China (Beijing) city (Table 3) was the main source of the lower non-carcinogenic risk when compared to Tehran city. Figure 4. TTHQ of BTEX in ambient air due to inhalation exposed population.

Carcinogenic Risk Assessment
The result of the carcinogenic risk assessment of benzene and ethylbenzene is presented in Table 6. Percentile 95% ECR of benzene and ethylbenzene was 1.25 × 10 6 and 1.11 × 10 6 , respectively (Table 6). Also, percentile 95% ECR of benzene and ethylbenzene was higher than the value of 1.00 × 10 6 . In this context, the population of Tehran is at considerable carcinogenic risk. These outcomes of the health risk assessment show that strict monitoring needs to be performed to control the concentration of BTEX in ambient air in Tehran city and BTEX standards should be revised as soon as possible.

Carcinogenic Risk Assessment
The result of the carcinogenic risk assessment of benzene and ethylbenzene is presented in Table 6. Percentile 95% ECR of benzene and ethylbenzene was 1.25 × 10 6 and 1.11 × 10 6 , respectively (Table 6). Also, percentile 95% ECR of benzene and ethylbenzene was higher than the value of 1.00 × 10 6 . In this context, the population of Tehran is at considerable carcinogenic risk. These outcomes of the health risk assessment show that strict monitoring needs to be performed to control the concentration of BTEX in ambient air in Tehran city and BTEX standards should be revised as soon as possible.

Conclusions
In the current study, the concentration of BTEX in Tehran ambient air was estimated based on a systematic review and meta-analysis approach and the non-carcinogenic and carcinogenic risks in the exposed population were estimated. The rank order of BTEX based on their concentration was benzene > o-xylene > ethylbenzene > toluene. The primary sources of benzene and toluene in ambient air of Tehran include both mobile and stationary sources of emission. Also, strong photochemical activities in the ambient air of Tehran were assumed. A health risk assessment based on the worse scenario (Percentile 95% THQ and ECR) indicated that the population of Tehran are at considerable non-carcinogenic and carcinogenic risks. Therefore, to reduce the health risks of BTEX, emission reduction plans should be implemented.