Health risk assessment of multiple exposure to 1, 3-butadiene, acrylonitrile, and styrene for manufacturing and operating workers

• Main Authors: Meng-YuWu, 吳孟禹
• Other Authors: Ching-Chang Lee
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/6ue63m

碩士 === 國立成功大學 === 環境醫學研究所 === 102 === Health risk assessment of multiple exposure to 1, 3-butadiene, acrylonitrile, and styrene for manufacturing and operating workers Meng-Yu Wu Ching-Chang Lee Department of Environmental and Occupational Health, Medical College, National Cheng Kung University SUMMARY The objectives of present research are to assess the exposure profile of 1,3-butadiene, acrylonitrile, and styrene for ABS manufacturing workers, and to explore the association between 1,3-butadiene, acrylonitrile, and styrene concurrent exposure with health outcomes. A analytical method was established to simultaneously analyze the urinary metabolites of 1,3-butadiene and acrylonitrile (DHBMA, MHBMA and CEMA), and then, the association between urinary metabolites concentrations with airborne 1,3-butadiene and acrylonitrile were examined to setup the exposure biomarker of 1,3-butadiene and acrylonitrile. In present research, the geometric mean of personal exposure concentrations of 1,3-butadiene, acrylonitrile, and styrene are 0.018 ppm, 0.051 ppm, and 0.032 ppm respectively. To evaluate the health outcomes of concurrent exposure to 1,3-butadiene, acrylonitrile, and styrene, the individual personal exposure level was divided individual permissible exposure level, then summate as concurrent exposure index (CEI). After excluded the worker who had alcohol drinking habit and grouped all the worker to high and low concurrent exposure group, the insulin (p=0.018)、leptin (p=0.019) and HOMA-IR (p=0.045) in high concurrent exposure group are significant higher than low concurrent exposure group. The urinary metabolites of 1,3-butadiene and acrylonitrile were analyzed by HPLC-MS/MS with Agilent ZORBOX Eclipse XDB-C18. After excluded smokers, the significant correlation between CEMA and airborne acrylonitrile was found. The results indicate that CEMA is good biomarker to represent the internal exposure to acrylonitrile. Only five workers’ lifetime carcinogen risk were higher than acceptable risk (10-3) which was calculated by back estimation of urinary CEMA. Key words: 1,3-butadiene, acrylonitrile, styrene, urinary metabolits, biological monitoring, concurrent exposure INTRODUCTION 1, 3-butadiene, acrylonitrile, and styrene are monomers for polymerization of rubber, especially for ABS rubber (Acrylonitrile-Butadiene-Styrene rubber). Butadiene had been classified as group 1 (carcinogenic to humans) and acrylonitrile and styrene had been classifiedas group 2B (possibly carcinogenic to humans) by International Agency for Research on Cancer (IARC). The major metabolites of 1,3-butadiene and acrylonitrile are DHBMA(1,2-dihydroxybutyl mercapturic acid), MHBMA (monohydroxy -3-butenyl mercapturic acid) and CEMA ((1-cyano-2-hydroxyethyl) cysteine) respectively. A 1,3-butadiene exposure study for workers in ABS factory reported that the high-exposure workers had lower glucose (GLU) and higher trigriceride (TG) which suggested that abnormal metabolism of glucose and lipid may resulted from high exposure to butadiene. The increasing incidence of Toxicant-Associated Steatohepatitis (TASH) was found in the workers who concurrent exposure to 1,3-butadiene, acrylonitrile, and styrene and may cause insulin resistant. 1,3-butadiene, acrylonitrile and styrene are operated together frequently, but little is known regarding the concurrent exposure to 1,3-butadiene, acrylonitrile, and styrene. Therefore, the objectives in this research are (1) to recognize the exposure profile for 1,3-butadiene, acrylonitrile, and styrene manufacturing and operating workers, (2) to explore the association between 1,3-butadiene, acrylonitrile, and styrene concurrent exposure and health outcomes, (3) to establish a method to simultaneously analyze the urinary metabolites of 1,3-butadiene and acrylonitrile, (4) to examine the representation of urinary metabolites for airborne 1,3-butadiene and acrylonitrile exposure, (5) to assess the health risk of 1,3-butadiene, acrylonitrile, and styrene exposure for manufacturing and operating workers. MTERIALS AND METHODS 102 workers in four ABS manufacturing and operating plants were recruited in this study. Airborne, blood and urine sample of those workers were collected after signing informed consent, and questionnaire was used to investigate workers’ life style, occupational history and disease history. Airborne sample was collected by charcoal adsorbent coated with 4-tert-butylcatechol (TBC), and the concentrations of 1,3-butadiene, acrylonitrile and styrene were analyzed by GC-FID. 30 mL Blood samples were collected from each worker as well as liver function tests and adipokines were examined. To evaluate the health outcomes of concurrent exposure to 1,3-butadiene, acrylonitrile, and styrene, the individual personal exposure level was divided individual permissible exposure level, then summate as concurrent exposure index (CEI).. A analytical method was established to simultaneously analyze the urinary metabolites of 1,3-butadiene and acrylonitrile (DHBMA, MHBMA and CEMA), and the representation of urinary metabolites for airborne 1,3-butadiene and acrylonitrile exposure were examined. Lifetime carcinogenic and non-carcinogenic risk was assessed by airborne concentration and back estimated concentration of urinary metabolites respectively. RESULTS AND DISCUSSIONS In our results, the geometric mean of personal exposure concentrations of 1,3-butadiene, acrylonitrile, and styrene are 39.94 μg/m3 (0.018 ppm), 109.59 μg/m3 (0.051 ppm),snd 137.94 μg/m3 (0.032 ppm), all lower than permissible exposure level (PEL), but, 3 workers’ acrylonitrile exposure concentrations are higher than PEL. To divide the workers to high- and low- exposure groups by job title, and compare the demographic data, airborne exposure levels of 1,3-butadiene, acrylonitrile, and styrene and blood biochemical index in these two groups. We found that the airborne exposure levels of 1,3-butadiene, acrylonitrile, and styrene n high exposure group were significant higher than low exposure group (1,3-butadiene：p=0.003, acrylonitrile：p=0.000, styrene: p=0.000) (table 1), and the habit of wearing personal respiratory protector between the two group are significantly difference (p=0.000). After excluded the alcohol drinking worker and grouped all the worker to high and low concurrent exposure group, the insulin (p=0.018), leptin (p=0.019) and HOMA-IR (p=0.045) in high concurrent exposure group are significant higher than low concurrent exposure group (table 2), it means concurrent exposure may cause metabolic abnormalities, even insulin resistant. Table 1. Airborne levels of 1,3-butadiene, acrylonitrile and styrene Item Unit High exposure group (n=72) Low exposure group (n=30) P-valueb 1,3-butadiene μg/m3 ND (ND-4751.01) a ND (ND- 474.18) 0.003* Acrylonitrile μg/m3 106.01 (ND- 14906.96) ND (ND- 1002.59) 0.000* Styrene μg/m3 218.21 (ND- 6570.75) ND (ND- 506.95) 0.000* a median(range) b Non-normal distribution，analysis by Wilcoxon rank sum test * p〈0.05 Table 2. Concurrent exposure Assessment (exclude alcohol drinking) CEI High CEI group (n=28) Low CEI group (n=51) P-value Insulin μU/mL 8.0 (3.3)a 7.5 (6.0) 0.018* Leptin μg/mL 8.5 (5.2) 5.9 (3.3) 0.019* HOMA-IR 1.8(0.8) 1.8 (1.5) 0.045* aMean(SD) The median (range) of urinary metabolites concentrations of DHBMA, MHBMA and CEMA at pre-shift are 270.26 (96.79-1347.06), 53.33 (3.04-1381.71) and 95.69 (2.82-5240.89) μg/g-cre, and at post-shift are 305 (87.28-869.27), 82.17 (11.76-402.76) and 270.02 (2.86-45646.49) μg/g-cre, respectively. After excluded smokers, the significant correlation between CEMA and airborne acrylonitrile was found (table 3); it means that CEMA is good biomarker for exposure to acrylonitrile. We developed a formula which was used to back estimate acrylonitrile exposure by urinary CEMA, and the result showed that personal protect equipment could efficiently decreased the exposure concentration of acrylonitrile. Table 3. Correlation between concentration of urinary metabolites with airborne levels of 1,3-butadiene and acrylonitrile (adjust smoking, PPE wearing and drinking) DHBMA MHBMA CEMA N=102 Pre-shift Post-shift Pre-shift Post-shift Pre-shift Post-shift 1,3-butadiene β= 0.88 p= 0.381 β= 1.791 p= 0.076 β= -0.381 p= 0.704 β= -0.203 p= 0.840 - - Acrylonitrile - - - - β= 4.051 p= 0.001 β= 2.005 p= 0.048 Only five workers’ lifetime carcinogen risk were higher than acceptable risk (10-3) which was calculated by back estimation of urinary CEMA. CONCLUSIONS This study is the first study that explored the association between 1,3-butadiene, acrylonitrile, and styrene exposure profile and health outcomes. We found that the airborne exposure levels of 1,3-butadiene, acrylonitrile, and styrene in high exposure group were significant higher than low exposure group (p〈0.005) by job title. Furthermore, we excluded the alcohol drinking worker and grouped all the worker to high and low concurrent exposure group and found the insulin (p=0.018)、leptin (p=0.019) and HOMA-IR (p=0.045) in high concurrent exposure group are significant higher than low concurrent exposure group. After excluded smokers, the significant correlation between CEMA and airborne acrylonitrile was found; it means that CEMA is good biomarker for exposure to acrylonitrile. According to the present study, 99% of 1,3-butadiene personal exposure levels was lower than 1.25 ppm, we suggested to modified the PEL of 1,3-butadiene from 5 ppm to 2 ppm. In present research, we found that the personal protect equipment could efficiently decreased the exposure concentration of acrylonitrile.