Distribution of volatile organic compounds around Ulsan Industrial Complexes and its possible health impact on the residents; a cross-sectional study

Abstract

Background

The Republic of Korea has undergone rapid industrialization, and still, the manufacturing sector mainly contributes to the economy. Ulsan is well known as the industrial city where two large-scale industrial complexes are located, and both have petrochemical and refining industries within them. Several studies have reported high ambient air pollution near petrochemical industries. Volatile organic compounds(VOCs) are one of the air pollutants emitted from the petrochemical industry known to pose adverse health effects on workers. However, studies on the impact of chronic exposure to low VOCs level are lacking. Therefore, this study aims to see the VOCs level near the industrial complexes and analyze the health impact.

Method

The Database based on the third phase of The Environmental Health Study in the Korean National Industrial Complexes (EHSNIC) in Ulsan conducted from 2018 to 2021 by the Environmental Health Center of Ulsan university hospital was used. Subjects were divided into the exposure and control group according to the estimated pollution level and distances from the industrial complex. Variables collected from the survey questionnaire, laboratory data, measurement data, and biological monitoring data were collected and analyzed. The VOCs levels and urinary metabolite levels were log-transformed before the statistical analysis.

Result

Among the total 1,234 subjects, 718 belonged to the exposure group, and 516 were in the control group. Benzene, ethylbenzene, and xylene were significantly higher in the exposure group. Urinary methyl hippuric acid, trans,trans-muconic acid, and mandelic acid were significantly higher in the exposure group compared to the control group, even after adjustment of the confounders.

Conclusion

We found out that residents living near the industrial complexes are exposed to higher VOCs levels, which is confirmed by the urinary metabolites concentration and personal monitoring VOC level. These results can draw attention to people engaged with environmental plans and used as primary data when making policies to reduce pollutant levels around industrial complexes.

Trial registration: IRB No. 2018-08-020

Background

The Republic of Korea underwent rapid industrialization in the 1960s, known as the “Miracle of Han River,” along with the change of industrial structure from agriculture to manufacturing. In the 1970s, the structural change within the manufacturing sectors had begun from light to heavy industries, which contributed to the nation becoming a global leader in electronics, appliances, and automobiles. Recently, there have been approximately 1,000 industrial complexes nationwide. Owing to rapid industrialization, the Gross National Income (GNI) per capita significantly increased, and the people’s awareness of environmental issues began to arise, especially among the residents living near the industrial complexes. When it comes to the industrial complex, Ulsan is known as a typical industrial city. The Ulsan National Industrial Complex, the large-scale petrochemical and refining, automobile, and shipbuilding industry designated to be the first industrial complex in 1962, is located and is in active operation now. Another major industrial complex in Ulsan is the Onsan Industrial Complex, also a large-scale petrochemical and nonferrous metal industry [1, 2]. Several studies have reported that various air pollutants are emitted from industrial activities, such as sulfur dioxide(SO₂), nitrogen dioxide(NO₂), carbon monoxide(CO), ozone, O₃, PM_2.5, PM₁₀, volatile organic compounds(VOCs), polycyclic aromatic hydrocarbons(PAHs) and heavy metals [3].

The concept of environmental disease drew the attention of people in 1985 when various health issues occurred among residents near the Onsan industrial complex. These are known as the Onsan pollution disease, the first environmental disease, and since then, environmental pollution by industrial complex has been identified as a significant public issue across the nation [4]. Outdoor and indoor air pollution is known to be the major environmental risk factors for several health conditions as well as mortality [5] [4] [6]. The source of air pollution can be natural or anthropogenic, and industrial complexes are the primary source of anthropogenic origin. [7] [8]. One of the main contributors to air pollution is volatile organic compounds, a group of cyclic hydrocarbons including benzene, toluene, ethylbenzene, and xylene (BTEX), which pose adverse effects on human health [6]. Studies on long-term monitoring of toxic pollutants from industrial facilities confirmed a significant exposure for inhabitants of these areas [9]. They are an important source in the formation of ozone and fine particulate matter and cause acute and chronic health outcomes, including irritation of the respiratory tract, neurological symptoms, and liver and kidney damage [10, 11]. The health impacts of VOCs are widely studied on short-term high-exposure areas such as occupational exposure, but areas of the long-term low-exposure are relatively underexplored.

Therefore, in this study, we aimed to investigate whether the VOCs level and health outcomes from those actually differ between the people residing in the vicinity of the industrial complex with people living far enough not to be affected directly by the pollution from the industrial complex. Furthermore, we are going to analyze the factors affecting the urinary metabolites of the VOCs.

Method

Result

 Table 1 shows the result of the demographic and residential character between the exposure and control groups. The mean age of the was 62.7±9.1, significantly higher than that of the control group, 55.7±7.6. Moreover, the significant difference in sex, smoking history, drinking history, occupational exposure, education, traffic load, and duration of residence was detected between the two groups. Man, smokers, without drinking history, occupational exposure, lower education status, lower traffic load, and longer duration of residence took up a higher portion in the exposure group compared with the control group. Only BMI did not show a significant difference. 

In terms of external exposure estimated by personal monitoring value described in table 2, benzene, ethylbenzene, and xylene were significantly higher in the exposure group. The level of styrene and toluene showed no significant difference in the two groups. 

*, p-value less than 0.05; **, p-value less than 0.001

The urinary metabolite concentration, which reflects the internal exposure, t,t-MA, MA, and MHA, were significantly higher in the exposure group compared to that of the control group even after adjustment of the confounders (Table 3). 

t,t-muconic acid(benzene), benzyl mercapturic acid(Toluene), Mandelic acid(Styrene), Phenylglyoxylic acid(Ethylbenzene, Styrene), S-phenyl-mercapturic acid (Benzene), Methylhippuric acid(Xylene)

§,p-value adjusted for age, sex, smoking history for t,t-MA, BMA, MA and PGA; p-value adjusted for age, sex, smoking history, ln(serum ferritin) for MHA

*, p-value less than 0.05; **, p-value less than 0.001

Table 4 shows the respiratory symptoms determined by the questionnaire answer. More subjects from the exposure group answered that to have suffered from sputum after waking up, sputum, dyspnea, wheezing, ever asthma symptom, ever allergic rhinitis symptoms significantly. 

†, who responded “yes” to the question “Have you ever experienced particular respiratory symptom?”

Among the disease history reported by the subjects (Table 5), subjects who had a history of hypertension, diabetes, anemia, and atopic dermatitis were more frequent in the exposure group significantly, while that of the thyroid disease were more frequent in the control group significantly.

Regarding laboratory measurement of the subjects described in Table 6, RBC, ferritin, BUN, and total IgE level were significantly higher in the exposure group. However, the platelet showed a lower level in exposure group compared to the control group significantly. WBC did not show a difference between the two groups.

From Table 7, all log-transformed benzene, toluene, ethylbenzene, xylene, and styrene levels were associated with each other to a certain degree. Among those, log-transformed xylene and ethylbenzene showed moderate correlation with a coefficient of 0.675. Log-transformed toluene showed a negative correlation with log-transformed MA, and log-transformed ethylbenzene showed a positive correlation with log-transformed MHA. Log-transformed xylene positively correlated with log-transformed MA and MHA (0.210 and 0.495, respectively). 

The result of multiple regression analysis to see the factors affecting urinary metabolite level are described in table 8. T,t-MA was tended to be higher in women by 0.255. MA level showed a positive relationship with xylene level and was negatively associated with ethylbenzene and education level. PGA level increases in smokers by 0.26, and BMA levels were negatively associated with education level. BMA level decreased in exposure group by 0.193. MHA level was positively associated with the smoking status and increased in the exposure group. Negative relationship was identified between the MHA level and the log-transformed ethylbenzene levels, traffic load and the occupational exposure. 

Discussion

In this study, we used pooled data from the survey, biological data, and exposure data from 2018 to 2021 to investigate the level of VOC exposure and the health effect of residents in vicinity of the industrial complex. From the results, subjects from the exposure group were exposed to higher pollutant levels than the residents living far from the industrial complex. Several studies have highlighted the higher ambient VOCs level area near the industrial complex, especially in petrochemical industries [6, 12–16]. Pinthong et al. used Positive Matrix Factorization(PMF) to evaluate the source of VOCs and showed that industrial processes and petrochemical industries were the major sources of the VOCs [6]. A study from Beijing also revealed that the main source of VOCs is the vehicle exhaust and industrial emissions [13]. The external VOC exposure assumed by the personal monitoring level showed that the exposure group was exposed to a higher VOC level compared to the control group, which is consistent with the previous studies. Bang et al. showed a higher BTX level in areas around industrial complexes by CMAQ simulation result [17]. Moreover, according to the Pollutant Release and Transfer Register(PRTR) data of Ulsan (Table 9), xylene and toluene are among the top 5 chemicals released in both Ulsan National and Onsan Industrial Complexes. Also from Fig. 2, higher amount of VOC release is demonstrated at the regions around the industrial complexes which is based on the emission data analysis from the Clean Air Policy Support System.

Biomonitoring of VOCs can be performed by various biological samples, including blood, urine, exhaled breath, and saliva [18]. In our study, we used the urinary metabolite of benzene, toluene, xylene, styrene, and ethylbenzene, which are t,t-MA, BMA, MHA, MA, and PGA, respectively. Responding to the high personal VOCs level, the internal exposure assumed by the urinary metabolite was also higher in the exposure group. The urinary t,t-MA, MA, and MHA were significantly higher in the exposure group. However, Gromiec et al. investigated association of the ethylbenzene exposure and excreted MA level, and found out that the excreted MA constituted 55 ± 2% of retained ethylbenzene. Also, many studies have used urinary MA as exposure monitoring for ethylbenzene and styrene.

The differences in health status reported by residents from each group were consistent with previous studies conducted on the health effects of industrial complexes. The respiratory symptoms except for cough were more frequently reported by the exposure group. Hong et al. investigated the pulmonary function level of the residents of the industrial complex and found out that pulmonary function was negatively affected by living in the vicinity of the industrial complex [7]. Others have reported that air pollution can increase the incidence of respiratory symptoms as well as cardiovascular symptoms.

It has been reported that chronic exposure to VOCs can induce chronic disease, respiratory disease, liver dysfunction, cancer, and allergic disease. Marquès et al. reviewed the health outcomes other than cancer in the population living near the petrochemical industrial complex. There, they revealed that most studies reported increased asthma and respiratory symptom prevalence both in children and adults [19]. In our study, wheezing, ever asthma symptom, ever allergic rhinitis symptom, and ever atopic dermatitis diagnosis were more frequent in the exposure group, which is consistent with other studies [20–24]. Elbarabry et al. investigated the association between long-term exposure to air pollution and anemia prevalence and showed that PM₁₀, PM_2.5, PM₁, and NO₂ were positively associated with the anemia prevalence and decreased hemoglobin levels significantly. The anemia reported by subjects in our study showed higher prevalence in the exposure group, but hemoglobin levels did not show a difference between the two groups [25]. Several studies on occupational or environmental exposure to VOCs can increase the risk of cardiovascular disease and have also been demonstrated by several animal studies as well. Everson et al. measured the BTEX and NO₂ exposure at the personal level and found out that those exposure and blood pressure have a positive association even in both short-term and long- term exposure as well as in lower concentrations [26]. Other than blood pressure, VOC is associated with increased cardiovascular mortality, heart failure hospitalizations, and ischemic heart disease mortality [27, 28], and the mechanism underlying these health risks is assumed to be through the endothelial damage. Moreover, VOCs can exert an effect on insulin resistance which is the main factor in the development of diabetes [27, 29–32]. Yang et al. also reported that high urinary t,t-MA increased the risk of diabetes regardless of smoking status and sex [33]. Sim et al. demonstrated that urine muconic acid and mono- (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) levels, which are metabolites of benzene and phthalate, increased the risk of metabolic syndrome even after adjusting for confounders by 1.34 and 1.39, respectively [34]. The result of our study did not show complete consistency with the previous studies as the design of the study and measurement method differ. The frequency of hypertension, diabetes, and anemia [35, 36] showed consistent result with previous studies while thyroid disease found out to be lower in exposure group. Allergic disease, respiratory disease, and cardiovascular disease showed no significant result between the two groups.

Chemicals of VOCs share common health risks, such as neurological and hematological effects, though each can express its specific health impact on the human body [37–39]. The health risks of each chemical component of VOCs are widely studied and confirmed in the context of occupational exposure where the exposure is in high concentration. The characteristic clinical finding of chronic benzene exposure is cytopenia which is manifested as anemia, leukopenia or thrombocytopenia demonstrated by several epidemiological studies even at low dose. According to a population-based study on the effect of BTEX exposure on hematological and biochemical indexes, BTEX and styrene significantly increased hemoglobin and total WBC count. Total xylene, styrene, and toluene show a positive association with the platelet level. Creatinine showed an inverse relationship with all VOCs. Lower GGT level was significantly associated with increased benzene and styrene levels, whereas, AST significantly increased with higher ethylbenzene, toluene, and total xylene level [40]. All VOCs showed a negative association with the creatinine level. Consistent with these results, RBC showed a higher level in the exposure group, while WBC, parameters of the liver function test, and creatinine level did not show a significant difference between the two groups. Another study on the hematological effect of BTEX exposure on tobacco-smoke non-exposed participants showed a negative association between BTEX and platelet level, which is similar to our study [41]. Although studies on VOC exposure and hematological parameters show controversial results in detailed parameters, the overall result reveals that VOCs can induce abnormal hematologic outcomes even at the environmental level.

Factors affecting the urinary VOC metabolites extensively varied across the researches. Smoking, drinking, BMI, simultaneous solvent exposure, work time, exposure gradient, climate, genetic factors, dietary intake, and ethnicities are factors that are suggested to affect urinary metabolite level, even though the results are controversial [42–47]. From the result of our study, t,t-MA was only significantly related to sex which is inconsistent with previous studies suggesting smoking and roast food intake are the factors affecting urinary t,t,-MA level [46, 48]. On the contrary, urinary MA showed an unexpected result. Even though urinary MA is a metabolite of styrene, xylene and ethylbenzene showed significant association as well as education level. Most studies have suggested that biomarkers of styrene and ethylbenzene have a significant positive association as those are the contents of tobacco smoke [44]. In accordance with the previous study, smoking increased the urinary PGA level significantly. Factors affecting urinary BMA were education level and traffic load. Previous studies suggested that smoking, sex, and age are the factors related to the toluene biomarker [49, 50]. In one study conducted with the first Korea National Environmental Health Study, urinary MHA was significantly associated with residential factors of the participants, including remodeling within 6 months and the existence of a major road within 100m of the residence [51]. Another study suggested that smoking is an important source of xylene exposure measured by urinary MHA, which is consistent with our result [52].

Our study has the following limitations:

1. Due to the cross-sectional design of this study, a causal relationship cannot be established.

2. Due to the nature of the annual project, the pollutant measurement data and biological sample data varied every year, resulting in an increase in missing values when pooling the database.

3. Measurement of health outcome variables was carried out using a questionnaire that heavily relied on participants' attitudes toward answering each question.

4. The temporality between the residence and disease occurrence cannot be confirmed.

5. Due to the nature of environmental exposure, exposure to VOCs cannot occur at a single pollutant level. Therefore, study on exposure to the multipollutant level is needed.

Usually, petrochemical industries give rise to benzene, toluene, xylene, and ethylbenzene together, so they exist in the air simultaneously, interacting with each other and with other air pollutants in the atmosphere [53]. Thus, to accurately estimate the public health risk from ambient VOCs level from the industrial complexes, assessment should be based on exposure to the whole BTEX mixture. Therefore, further study is needed to make up for the limitations of our study to clarify the effect of ambient pollutant levels on the health outcomes. Despite these limitations, this study accumulated annual data to construct 4 year pooled database to analyze the difference in pollutant levels and health outcomes between residents of the industrial region and control region. Also, previous studies on the health effects of ambient VOC exposure mostly used estimated exposure levels using modeling techniques, but our study measured personal monitoring data. Apart from external exposure data assumed by personal monitoring data, we were able to presume the internal exposure using urinary metabolite level.

This study showed that residents living near the industrial complex are exposed to higher VOCs level, confirmed by personal monitoring data and biological monitoring data which stands for internal exposure. Furthermore, even though a causal relationship cannot be confirmed, respiratory symptoms and some chronic diseases were more frequent among the residents living near the industrial complex as well as abnormal hematologic parameters. The result of our study can be used to raise awareness among policymakers and employers to develop countermeasures to regulate the environmental pollution from the industrial complexes. Moreover, it can be used as basic data when establishing plans to reduce the VOCs exposure to manage the health of residents of the industrial complexes.

Conclusion

Ulsan is an industrial city where large-scale Industrial Complexes are located. The petrochemical industries are primarily in operation and concerns about health effects from the VOCs exposure have been raised. From this study, we found out that residents of 2 major Industrial complex, Ulsan National and Onsan Industrial Complex, were exposed to higher level of VOCs and respiratory symptoms were more frequently detected among them compared to the control population. Our result can be served as basic information when establishing an environmental policy to promote health of population living near industrial complexes.

Abbreviations

Declarations

Ethics Approval and consent to participate

This study was approved by the Institutional Review Board of the Ulsan University Hospital (IRB File No. 2018-08-020). All subjects were provided written consent and agreed on the participation of the project. 

Availability of data and materials

The data used in this study are based on the national project “Evaluating of Exposure to Environmental Pollutants and Health Effects of Inhabitants in Industrial Complexes Area(3rd stage)- (Ulsan·Onsan, 4th year)”. Therefore, the data is not publicly available.   

 Competing interest

All authors declare that they have no conflict of interest.

Funding

This research was supported by the Inha University Hospital's Environmental Health Center for Training Environmental Medicine Professionals funded by the Ministry of Environment, Republic of Korea (2022)

Authors’ contribution

“ARK, JL, and YO conceptualized the overall research.; ARK, JH, and IO discussed the methodology.; Manuscript was validated by CY, YK, CS, and IO.; ARK and JHB did the formal analysis.; ARK, YO, and JHB were engaged in the data curation; ARK wrote the original manuscript.; ARK, JL, and JHB reviewed, and the final edition was done by ARK.; JHB visualized the figures.; JL, YK, CY, CS, and IO provided supervision.; All authors have read and agreed to the published version of the manuscript.” The author(s) read and approved the final manuscript. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Jiho Lee.

Acknowledgement

The authors thank residents who decided to participate in the the third phase of “The Environmental Health Study in the Korean National Industrial Complexes (EHSNIC)”. We are grateful to the Ulsan Metropolitan City Environmental Health Center, Ulsan University Hospital for providing the database. We thank Andrew Jones for his thoughtful guidance on the project. 

Author’s information

Occupational and Environmental Medicine, Ulsan University Hospital, 25, Daehakbyeongwon-ro, Dong-gu, Ulsan city, Republic of Korea

Jiho Lee, A Ram Kim, Yangho Kim, Cheolin Yoo, Changsun Sim

Ulsan Metropolitan City Environmental Health Center, 25, Daehakbyeongwon-ro, Dong-gu, Ulsan, Republic of Korea

Yeonsuh Oh, Jin Hee Bang, Inbo Oh

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