Annals of Occupational and Environmental Medicine

Original Article

Association between urinary trans,trans-muconic acid and diabetes: a cross-sectional analysis of data from Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015–2017): Eun Hye Yang, Do Jin Nam, Hyo Choon Lee, Soon Su Shin, Jae-Hong Ryoo; Ann Occup Environ Med 2021;33:e35. Published online December 6, 2021; DOI: https://doi.org/10.35371/aoem.2021.33.e35

Abstract Abstract in Korean PDF Supplementary Material PubReader ePub

Background

Benzene is a ubiquitous air pollutant that is well known to cause hematopoietic effects in humans including leukemia. Recently, several studies have discussed its non-carcinogenic effects such as diabetes. This study aimed to investigate the association between diabetes and urinary trans,trans-muconic acid (t,t-MA), one of benzene metabolite, using adult data from Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015–2017).

Methods

This study analyzed 3,777 adults (1,645 men and 2,132 women) from the KoNEHS cycle 3 (2015–2017). The distribution and fraction of each independent variable were presented separately according to the urinary benzene metabolite levels (t,t-MA quartiles) and diabetes to determine the general characteristics of the subjects. Odds ratios (ORs) were calculated using logistic regression after stratification by gender and smoking status to identify the association between urinary t,t-MA and diabetes.

Results

Compared with the first quartile (reference), the risk of diabetes significantly increased above the 4th (1.834 [1.107–3.039]) quartile in men and above the 3rd (1.826 [1.095–3.044]) and 4th (2.243 [1.332–3.776]) quartiles in women after adjustment. Stratified analysis based on smoking revealed that the ORs for the 3rd (1.847 [1.146–2.976]) and 4th (1.862 [1.136–3.052]) quartiles in non-smokers and those for the 2nd (1.721 [1.046–2.832]), 3rd (1.797 [1.059–3.050]), and 4th (2.546 [1.509–4.293]) quartiles in smokers were significantly higher.

Conclusions

We confirmed that urinary t,t-MA is significantly associated with diabetes regardless of gender and smoking status. And further studies are necessary to access the clinical impacts of this findings.

소변 내 뮤콘산 농도와 당뇨의 연관성 : 제 3기 국민환경보건기초조사(2015-2017)를 이용한 단면연구
목적
본 연구는 일반인구집단을 대상으로 환경적인 벤젠 노출과 당뇨와의 연관성을 알아보기 위해 제 3기 국민환경보건기초조사 성인 데이터를 이용하여 벤젠 대사물질 중 하나인 소변 내 뮤콘산의 농도와 당뇨와의 관계를 알아보았다.
방법
제 3기 국민환경보건기초조사 성인 3,777명(남성 1,645명, 여성 2,132명)을 분석하였다. 대상자의 일반적인 특성을 확인하기 위해 각 독립변수의 분포 및 분율을 소변 내 뮤콘산 농도(사분위수)와 당뇨유무에 따라 제시하였다. 소변 내 뮤콘산 농도와 당뇨와의 연관성을 알아보기 위해 성별과 흡연으로 각각 층화 후 로지스틱 회귀분석을 사용하여 오즈비를 구하였다.
결과
보정 후, 남성은 제 4사분위 구간 1.834(1.106-3.039), 여성은 제 3사분위 구간 1.825(1.095-3.044), 제 4사분위 구간 2.241(1.331-3.773)에서 오즈비가 유의하게 증가하였으며, 소변 내 뮤콘산 농도가 증가할수록 당뇨위험이 증가하는 경향성을 보였다. 흡연으로 층화 후 분석한 결과 비흡연자의 경우 제 3분위수 1.847(1.146-2.976), 제 4분위수 1.861(1.135-3.050), 흡연자의 경우 제 2분위수 1.721(1.046-2.832), 제 3분위수 1.796(1.058-3.048), 제 4분위수 2.544(1.509-4.291)가 보정 후 통계적으로 유의하였다.
결론
본 연구에서 벤젠 대사체인 소변 내 뮤콘산 농도가 성별과 흡연 상태에 관계없이 당뇨와 유의하게 관련이 있다는 것을 확인하였으며, 추후 환경적인 벤젠 노출에 대한 당뇨 연관성에 대하여 연구가 필요하다.

Citations

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Association Between Benzene and Other Volatile Organic Compounds Exposure and Diabetes Mellitus Among Korean Adults: Findings from the Nationwide Biomonitoring Data
Seong-Uk Baek, Minseo Choi, Yu-Min Lee, Jin-Ha Yoon
Exposure and Health.2024;[Epub] CrossRef
Distribution of volatile organic compounds by distance from industrial complexes and potential health impact on the residents
A Ram Kim, Jin-Hee Bang, Sunghee Lee, Chang Sun Sim, Yangho Kim, Jiho Lee
International Journal of Environmental Health Research.2024; : 1. CrossRef
Association of Urinary Benzene Metabolite and the Ratio of Triglycerides to High-Density Lipoprotein Cholesterol: A Cross-Sectional Study Using the Korean National Environmental Health Survey (2018–2020)
Seungju Baek, Eunjung Park, Eun Young Park
Toxics.2023; 11(12): 985. CrossRef
Exploration of an Area with High Concentrations of Particulate Matter and Biomonitoring Survey of Volatile Organic Compounds among the Residents
Hyunji Ju, Seungho Lee, Jae-Hee Min, Yong-Sik Hwang, Young-Seoub Hong
Journal of Environmental Health Sciences.2023; 49(6): 344. CrossRef
Association of metabolites of benzene and toluene with lipid profiles in Korean adults: Korean National Environmental Health Survey (2015–2017)
Soon Su Shin, Eun Hye Yang, Hyo Choon Lee, Seong Ho Moon, Jae-Hong Ryoo
BMC Public Health.2022;[Epub] CrossRef

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Original Article

Urinary Hippuric Acid and trans,trans-Muconic Acid Levels According to Commuting Mode and Duration, Residential Environment, and Intake of Preservative-Added Foods and Beverages in University Students: Kyoung Mee Kim, Sang Yong Eom, Dong Hyuk Yim, Sun In Moon, Yong Dae Kim, Heon Kim; Korean Journal of Occupational and Environmental Medicine 2012;24(1):61-71. Published online March 31, 2012; DOI: https://doi.org/10.35371/kjoem.2012.24.1.61

Abstract PDF

OBJECTIVES
Automobile exhaust gases contain benzene and toluene, which are excreted in human urine as trans,trans-muconic acid and hippuric acid, respectively. Sorbic acid and benzoic acid, used as food preservatives, are also metabolized into trans,trans-muconic acid and hippuric acid in the human body. The purpose of this study is to estimate the level of benzene and toluene exposure according to the commuting mode and duration, residential environment, and preservative-added foods intake in university students who are not occupationally exposed to benzene or toluene.
METHODS
Spot urine samples were collected from 211 university students who had no occupational exposure to volatile organic compounds. Information about their smoking history, residence type, traffic environments, commuting mode and duration, and their intake of bottled or canned food or beverages was gathered through a self-administered questionnaire. Urinary concentrations of trans,trans-muconic acid and hippuric acid were measured and statistically correlated to the individual's life style factors.
RESULTS
There was no significant difference in the urinary concentrations of trans,trans-muconic acid or hippuric acid according to the smoking history. Mean urinary concentration of hippuric acid in females was higher than that found in males. Subjects living in districts with a population density of 1,000~4,999 people/km2 showed the highest urinary hippuric acid level; individuals living in cities of 5,000~9,999 people/km2 population density were next. The mean urinary trans,trans-muconic acid concentration was higher in students who were living where traffic jams are common compared to those who did not, and in subjects whose residence were within 149 m from a 4-lane road compared to those whose residence was not. However, neither mode nor duration of the commute showed any effect on the urinary trans,trans-muconic acid or hippuric acid concentrations of the students. Urinary hippuric acid levels increased when consuming canned fruit or canned coffee, and urinary trans,trans-muconic acid levels increased when consuming fruit juices or pickled radishes.
CONCLUSIONS
The inhalation of vehicle exhaust and the ingestion of canned or pickled food may increase urinary hippuric acid and trans,trans-muconic acid levels in individuals who are not occupationally exposed to benzene or toluene.

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Comparative Analysis of Heavy Metal Exposure Concentrations and Volatile Organic Compound Metabolites among Residents in the Affected Area According to Residential Distance from a Coal-fired Power Plant
Jee Hyun Rho, Byoung-Gwon Kim, Jung-Yeon Kwon, Hyunji Ju, Na-Young Kim, Hyoun Ju Lim, Seungho Lee, Byeng-Chul Yu, Suejin Kim, Young-Seoub Hong
Journal of Environmental Health Sciences.2024; 50(1): 25. CrossRef
Association of Urinary Benzene Metabolite and the Ratio of Triglycerides to High-Density Lipoprotein Cholesterol: A Cross-Sectional Study Using the Korean National Environmental Health Survey (2018–2020)
Seungju Baek, Eunjung Park, Eun Young Park
Toxics.2023; 11(12): 985. CrossRef
Concentration of volatile organic compounds(VOCs) in ambient air and level of residents in industrial area
Kyungsook Woo, Heejin Park, Tackshin Kang, Geunbae Kim, Junmin Jeon, Bongki Jang, Jongwha Lee, Busoon Son
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(1): 104. CrossRef

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Original Article

Relationship Between Urinary t, t-muconic Acid and Insulin Resistance in the Elderly: Hyun Seung Park, Jeong Cheol Seo, Jin Hee Kim, Sang Hyuk Bae, Youn Hee Lim, Soo Hun Cho, Yun Chul Hong; Korean Journal of Occupational and Environmental Medicine 2011;23(4):387-396. Published online December 31, 2011; DOI: https://doi.org/10.35371/kjoem.2011.23.4.387

Abstract PDF

OBJECTIVES
To examine the associations between the urinary t, t-muconic acid (t, t-MA) concentration and three indices of insulin resistance; namely, the homeostasis assessment of insulin resistance (HOMA-IR) index, blood insulin level and fasting glucose level.
METHODS
A panel study was performed on the elderly at a public health care center population in the northern area of Seoul between 2008 and 2010. The participants were 560 elderly, over 60 years of age whose urinary t, t-MA and insulin resistance indices had been measured; questionnaires were completed by these participants. A generalized linear mixed (GLM) analysis was adjusted for age, sex, drinking, urinary cotinine, exercise, vitamin intake and body mass index, at a significance level of p<0.05.
RESULTS
A total of 411 participants were finally analyzed after excluding those with diabetes and only one visit to the public health care center. Higher urinary t, t-MA concentrations were linearly associated with the HOMA-IR index, blood insulin level and fasting glucose level in the simple and fully adjusted GLM models. Although there were few limitations, a portion of insulin resistance was proven to be explained by exposure to benzene using r-squared. A significant relationship was also observed between urinary t, t-MA and malondialdehyde (MDA) using the same GLM models.
CONCLUSIONS
Urinary t, t-MA is related to the development of insulin resistance which is a key factor for development of diabetes and its complications induced by oxidative stress.

Citations

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Exploration of an Area with High Concentrations of Particulate Matter and Biomonitoring Survey of Volatile Organic Compounds among the Residents
Hyunji Ju, Seungho Lee, Jae-Hee Min, Yong-Sik Hwang, Young-Seoub Hong
Journal of Environmental Health Sciences.2023; 49(6): 344. CrossRef
Association between urinary trans,trans-muconic acid and diabetes: a cross-sectional analysis of data from Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015–2017)
Eun Hye Yang, Do Jin Nam, Hyo Choon Lee, Soon Su Shin, Jae-Hong Ryoo
Annals of Occupational and Environmental Medicine.2021;[Epub] CrossRef

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2 Crossref

Original Article

The Association between Trans, Trans-Muconic Acid as a Biomarker for Benzene Exposure and the Platelet Count: Young Sun Min, Kuck Hyun Woo, Jin Seok Kim, Jay Young Yoo, Kwan Lee, Hyun Sul Lim, Heon Kim; Korean Journal of Occupational and Environmental Medicine 2010;22(2):95-101. Published online June 30, 2010; DOI: https://doi.org/10.35371/kjoem.2010.22.2.95

Abstract PDF: OBJECTIVE: Recent researches suggest that trans,trans-muconic acid (t,t-MA) would be an adequate metabolic biomarker for low-level benzene exposure. Few study have investigated the association between the t,t-MA and platelet count, and this is the primary aim of this study.
METHODS
From May 2004 to June 2004, 326 chemical factory workers took part in a questionnaire survey and they underwent urinary t,t-MA and CBC assessment. The questionnaire covered general aspects of health and the occupational and smoking histories. Statistical analyses of outcomes were performed using SPSS 14.0 for Windows.
RESULTS
The subjects' urinary t,t-MA concentration (geometric mean and geometric standard deviation) was 0.28 mg/g creatinine (2.62). No significant differences between different occupations among the chemical workers were found. The urinary t,t-MA concentrations in the smokers and non-smokers were 0.32 mg/g creatinine (2.44) and 0.25 mg/g creatinine (2.77) respectively, and the difference was statistically significant (p<0.05). There was no significant difference in the platelet count based on occupation and the smoking history. There was significant correlation between log(platelet) and log(t,t-MA)(r=-0.116 p=0.039). The regression equation log(platelet) = -0.002xAge + [-0.029xlog(t,t-MA)] + 2.436, R2=0.032, was calculated from linear regression analysis with log(platelet) as the dependent variable. Cross-tabulation between 2 subgroups that were divided by the 90-percentile level of the t,t-MA (0.819 mg/g creatinine), and 2 subgroups that were divided by the 10-percentile level of the platelet count (175,000) was conducted. Higher distribution in subgroup with platelet count below 175,000 was demonstrated in the subgroup with a urinary t,t-MA above the 90-percentile, with an odds ratio of 3.01.
CONCLUSIONS
The study may be limited by not taking into account factors such as smoking quantity and sorbic acid, which may confound urinary the t,t-MA concentration as well as medication and infection that may affect the platelet count. Yet it is meaningful that the correlation between the urinary t,t-MA concentration and the platelet count was found through linear regression analysis and the chi-square test, and further, this outcome may be used as a basis for a study to establish the acceptable limit of urinary t,t-MA in Korea.

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Original Article

Change of Urinary Trans, Trans-Muconic Acid before and after Turnaround Process in a Petrochemical Plant: Seung Hyun Kim, Ji Ung Park, Jai Dong Moon; Korean Journal of Occupational and Environmental Medicine 2008;20(4):335-342. Published online December 31, 2008; DOI: https://doi.org/10.35371/kjoem.2008.20.4.335

Abstract PDF

OBJECTIVES
This study was performed to estimate the exposure to benzene, one of the most serious health hazards, in four phases of a turnaround in a petrochemical company, and to evaluate the suitability of trans,trans-muconic acid (tt-MA) to act as a biomarker of exposure to low benzene levels.
METHODS
tt-MA was determined in 152 urine samples collected in 4 phases ('before daily work', 'after daily work', 'purge', and 'inspection' of turnaround work) from 19 exposed workers involved in turnaround work and 19 clerical workers. The ambient benzene levels were monitored simultaneously during the 'purge' process of turnaround work in the exposed group.
RESULTS
The median urinary tt-MA for the 4 phases was 0.046 mg/L, 0.082 mg/L, 0.507 mg/L, and 0.468 mg/L in the exposed group and 0.050 mg/L, 0.065 mg/L, 0.269 mg/L, and 0.331 mg/L in the clerical workers, respectively. The median urinary tt-MA for the exposed group was significantly higher than that of the clerical workers during the purge process (P<0.05). In the exposed group, median urinary tt-MA for the 'before daily work' phase was significantly lower than that of the other three phases (P<0.05). Even in the clerical workers, the urinary tt-MA level for the 'before daily work' phase was significantly lower than that of the turnaround (P<0.05). There was a very significant correlation between urinary tt-MA levels and ambient benzene levels (r(s) = 0.795, P<0.01).
CONCLUSION
The turnaround process increased the benzene exposure for all workers, even the clerical workers, in a petrochemical company handling benzene. Urinary tt-MA was found to be suitable as a biomarker for the exposure to low-level benzene.

Citations

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Estimating Benzene Exposure Level over Time and by Industry Type through a Review of Literature on Korea
Donguk Park, Sangjun Choi, Kwonchul Ha, Hyejung Jung, Chungsik Yoon, Dong-Hee Koh, Seunghun Ryu, Soogeun Kim, Dongmug Kang, Kyemook Yoo
Safety and Health at Work.2015; 6(3): 174. CrossRef
The Relationship between Exposure to Benzene and the Excretion of Urinary Trans, Trans-muconic Acid in Petrochemical Factory Turnaround Process Workers
Seung Min Lee, Jong Uk Won, Chi Nyon Kim, Jaehoon Roh
Journal of Korean Society of Occupational and Environmental Hygiene.2014; 24(1): 52. CrossRef

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Original Article

Effect of Genetic Polymorphisms of CYP2E1 and ALDH2 on the Relationship between the Levels of Urinary 8-Hydroxydeoxyguanosine and t,t-Muconic Acid: Yong Dae Kim, Jong Won Kang, Sang Yong Eom, Yan Wei Zhang, Sung Hoon Kim, Eun Young Kim, Chul Ho Lee, Jai Dong Moon, Heon Kim; Korean Journal of Occupational and Environmental Medicine 2007;19(2):164-170. Published online June 30, 2007; DOI: https://doi.org/10.35371/kjoem.2007.19.2.164

Abstract PDF: OBJECTIVES
This study was performed to investigate the effect of genetic polymorphisms on the oxidative genetic damage caused by benzene exposure in workers.
METHODS
We measured urinary t,t-muconic acid levels as a biomarker for benzene exposure and measured the level of urinary 8-OHdG to assess oxidative DNA damage in benzene-exposed healthy male workers. Genetic polymorphisms of ALDH2 and CYP2E1 were determined by TaqMan assay. We estimated Pearson correlation coefficients between urinary t,t-muconic acid and 8-OHdG according to the genetic polymorphisms of CYP2E1 and ALDH2.
RESULTS
There was a significant relationship between urinary t,t-muconic acid and 8-OHdG concentrations in overall subjects (R=0.532, p<0.001). Smokers showed a higher correlation coefficient between the markers than nonsmokers did (R=0.520 vs. 0.010). Individuals with CYP2E1 c1/c1 genotype also showed a higher correlation coefficient between them than those with CYP2E1 c1/c2 or c2/c2 genotypes (R=0.670 vs. -0.145). In multiple linear regression analysis including smoking status, sorbic acid intake, age and genetic polymorphisms of CYP2E1 and ALDH2 as the independent variables, urinary t,t-muconic acid showed a significant association with urinary 8-OHdG.
CONCLUSIONS
There was a significant correlation between urinary 8-OHdG and urinary t,t-muconic acid in benzene-exposed workers. This relationship was affected by genetic polymorphisms of CYP2E1and ALDH2.

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