MINIST RY OF EDUC ATION AND TRAI NING MINI STRY OF HEALTH HANOI MEDICAL UNIVERSITY _ DANG THI TRANG DETERMINATION OF URINARY MANDELIC AND PHENYLGLYOXYLIC ACIDS IN ETHYLBENZENE-EXPOSED PAINT MANI FACT I RING WORKERS IN 2019 Major : Preventive Medicine Doctor Code : D72O3O2 THESIS OF GRADUATION MEDIC AL DOCTOR COURSE 2015 2021 Supen isor Ac%oc Prof Khuong Van I)u\ Phil MD Va Xu an Tiling Hanoi -2021 «s> ■> ACK NOW J DG N IE\ T I would like to offer my thanks to the Boards of Hanoi Medical Universin' Institute of Preventive Medicine and Public Health, as well as the teachers of the Department of Occupational Health for supporting me to this thesis in the most convenient conditions I would like to express my great appreciation to all the individuals and teams below, that without them would not be able to accomplish my dissertation Firstly I would like to express my deepest gratitude to my supervisor AProf Khuong Van Duy for his patient guidance, enthusiastic encouragement and useful critiques of this research work His willingness to give Ins time so generously has always been very much appreciated Not only did I leant a lot from his academic knowledge, but also his enthusiasm and professional attitude towards work inspired me to pursue my career I would like to offer my special thanks to PhD MD Vu Xuan Trang subject "Determination urinary Mandelic and Phenvlglyoxylic acids in ethylbenzene exposed pain! manufacturing workers and associated factors 2019"- Code: 218 Ơ7TLĐ for creating conditions for me to use data to write this thesis Last but not least I would like to give thanks to my family and close friends, for their support and encouragement throughout my study Hanoi May 2021 Dang Thi Trang COMMITMENT Respectfully addressed to: - Board of Hanoi Medical Uni versify - Board of Institute for Preventive Medicine and Public Health - Department of Population - Board of Dissertation Assessment My name is Dang Thi Trang • student of Hanoi Medical University, course 2015 - 2021 majoring in Preventive Medicine Doctor, hereby declare that; This is a research that I participated under the scientific guidance of Assoc Prof Khuong Van Duy and P11D MD Vu Xuan Trung The research content and research results in this topic are truthful This study is part of the project "Xghỉén CÚ1I XỂC định mứe (lộ thâm tháu cua Ethylbenzene thõng qua sán phúm chuyên hóa acid mandelic (MA) vã add phenylglyoxylic (PGA) nước tiêu u người hu (lộng có tiếp xúc"- Code: 2IX 071 LI) by PhD MD Vu Xuan Tnrng who is Director of rhe Center for Occupational Health is the project manager in 2019 The author has allwed me to participate in the process of data processing, analysis and use of this data for my graduation thesis In addition, the thesis also uses a number of comments, assessments as well as data from other authors agencies and organizations, all with source annotations clearly stated in the references If I find any fraud I take full responsibility for the content of my thesis The aut hor of the thesis Dang Thỉ Trang TABLE OF CONTENTS INTRODUCTION _ I CHAPTER 1: LITERATURE REMEW — 1.1 Concepts and definitions a I • • • ^^mploycc ■ a aa a a a .« a aa ■ a a a a a a • 8 aa a aa • ■ a a a ■ • • a ■ a a a a a a • a a aa a «a a a ■ a a a a • ■ a a a • I 1.2 Occupational disease 41 (itMUii H Illi uulu ãããããôôãã MIMI IIIMIIIIUM ô3 1.1.3 Volatile organic compounds (VOC) 12 Characteristics of ethylbenzene 1.2.1 Chemical and physical data, production and usage status 1.2.2 Exposure, penetration, metabolism, and excretion 1.2.3 The effect of ethylbenzene 1.3 Research on exposure and biological monitoring of ethylbenzene exposed*) 1.4 Associated factors impact on the lex-el of tire urinary Mandelic and Phenylglyoxylic acids in ethylbenzene-exposed paint manufacture worker's 12 1.4.1 Associated factors among the concentration of urinary MA PGA 12 I 4.2 High performance liquid chromatographic (HPLC) for Determination of Urinary Metabolites of Ethylbenzene 13 1.5 Paim industry in Vietnam 13 1.6 Paint companies in Hung Yen and Hanoi 14 CHAPTER 2: METHODS 16 2.1 Study'subjects 16 2.1.1 Study subjects 16 2.1.2 Inclusion criteria 16 2.1.3 Exclusion criteria 16 2 Location and ti me of study 16 2.2.1 Research location 16 «s> ■> 2.2.2 Research time 16 23 Research Methods 16 23.1 Study design 16 3.2 Sample size and sampling method 17 2.2.3 Research variables and indicators 17 23.4 Instruments 19 ♦r •• 23.5 Data collection 19 23.6 Sample analysis at the laboratory 20 23.7 Evaluation critena 2.3.8 Data analysis ãã ôããã 23 23.9 Bias and bias control 23 2.3.10 Ethical consideration 24 CHAPTER 3: RESULTS •••MM 25 25 3.1 Characteristics of participants 32 Ethylbenzene and Styrene concentration in the working enxironment 27 3 The lex-el of urinary MA and PGA in ethylbenzene-exposed paint manufacturing workers C HAPTER 4: DISCUSSION 38 4.1 Characteristics of participants 38 Ethylbenzene and Styrene i n the working enxironment— 38 4.3 The lex-el of ethylbenzene contamination though MA and PGA metabolism products in urine 41 4.4 Limitationofthe study 45 CONCLUSION 46 RECOMMENDATIONS—— 47 REFERENCES APPENDIX -w ã5 Vi ô s -I -4: ABBREVIATIONS ACGIH The American Conference of Governmental Hygienist BTEX Benzene, toluene, ethylbenzene, xylene BTX Benzene, toluene, xylene CNS Central nervous system EB Ethylbenzene EBS Ethylbenzene and styrene EPA Environmental protection agency HPLC High performance liquid chromatographic ĨARC International Agency for Research on Cancer MA Mandelic Acid NIOSH National Institute for Occupational Safety and Health OSHA Occupational Safety and Health Administration PGA Phenylglyoxylic Acid vocs Volatile organic compounds GCMS Chromatography Mass Spectometrv Cre Creatinin 1ARC International Agency for Research on Cancer Industrial LIST OF TABLES Table 2.1: Variables and research indicators 17 Table 2.2: Process and equipment used in the laborator 20 Table 2.3: Acceptable concentrations of ethylbenzene and styiene in the working environment 22 Table 3.1: Demographic characteristics of participants 25 Table 3.2: Characteristic of participants in the working process 26 Table 3.3: Lifestyle habits of participants 26 Table 3.4: Distribution of ethylbenzene and styrene samples exceeded the peimissible limit in the working environment 27 Table 3.5: The average concentration of Ethylbenzene and styrene in the working environment 28 Table 3.6: Individual Ethylbenzene and Styrene samples that exceeded the permissible limit ~ 29 Table 3.7: Individual ethylbenzene and styrene concentration (8 hours) 30 Table 3,8; Urinaiy MA and PGA acids concentration 32 Table 3.9: Total unitary concentration of MA and PGA _ 32 Table 3.10: Total concentration of MA- PGA by age 33 Table 3.11: Total concentration of MA- PGA by working period 34 Table 3.12: Total concentration of MA- PGA by working position 35 Table 3.13: Total concentration of MA- PGA by paint companies 36 IJ ST OF FIGI RES Figure 1.1: Ethylbenzene metabolism in tile human body F igure 2.1: The process of sampling and analysing ethylbenzene and styrene in the workers’ ambient air 19 Figure 3.1: Total concentration of MA and PGA in participants 33 Figure 3.2: Correlation between ethylbenzene concentration and the total concentration of MA and PGA in the urine 37 -w ã* CN ôG ABTRACTS Background: Currently, many countries have used the ethylbenzene metabolic products in urine is MA and PG/\ as biological monitoring index for ethylbenzene-exposed workers There is no biological monitoring for ethylbenzene in Vietnam The research aimed to: Determine ethylbenzene and styrene concentrations in the working environment through environmental monitoring and individual dose monitoring, and Determine the level of urinary MA and PGA in ethylbenzene-exposed paint manufacturing workers in 2019 Methods: A cross sectional study was conducted in Painting Company from January 2019 to April 2021 SPSS and Miiútab software described frequency tables; Pearson's correlation evaluated the correlation of ethylbenzene concentration in the working emironment with ethylbenzene's metabolite in urine Results: The average ethylbenzene and styrene concentrations in the working environment was 49.58 ± 34.67mg/m\ and 1.13 ± 0.97 mg/mJ respectively (within the permissible limit) The individual ethylbenzene concentration (8 hours) in the Mixing group was 99.77 ± 62.72 mg m' and in the Quality Control and Packing group was 19.58 ± 17.0" mg'n? The average concentration of urinary MA and PGA were 77.21 - 75.I8mg.'g creatinine and 46.58 = 51 "6mg/g creatinine respectively The total axeiage concentration of MA - PGA was 123.08s 101.83nig’g creatinine Correlation coefficient between ethylbenzene concentration and the total concentration of MA and PGA in tire urine was 0.82 Conclusion: The maximum concentration of ethylbenzene and sty rene at research ốcỉliões was within the- permissible limit- The average total concentration of MA and PGA in the three companies were within the permissible limit according to ACGIH Tliere is a strong correlahcn between ethylbenzene exposure and the metabolite in the urinaryi.MA and PGA) (r - 0.82) Key words: MA PGa Ethylbezene Ethylbenzene-exposed Styrene 46 CONCLUSION Concentration of ethylbenzene anil styrene in the working environment • The maximum concentration of ethylbenzene and styrene at three research facilities was within the permissible limit Significantly the concentration of styrene in the environment is very low (1.13 ± 0.97mg,mi), - 22 individual ethylbenzene concentrations samples in an average 8-hour at research facilities exceeded the permissible limit by ACGIH mainly in the mixing workshop The level of ethylbenzene contamination through Mandelic and Phenylglyoxylic add* merabolhm products in urine • The average total concentration of MA and PGA in the three companies were within the permissible limit according to the ACGIH but calculated for each subject 21 samples are exceeding the permissible limit - There is a suông correlation between ethylbenzene exposure and the metabolite in the urinary(MA and PGA»(R ■ 0.82) 47 RECOMMENDATIONS From the research results, we have the following recommendations: • Apply individual dose monitoring (monitoring shifts) substitute for currently environmental monitoring ’ Set up the permissible limn for ethylbenzene m the working environment - In the working environment, styrene concentration and the individual dose of the workers are much lower than the permissible limit Need to rebuild the limit to match reality • Apply MA and PGA concentration indexes as biological monitoring index with the permissible limit for ethylbenzene exposure (0.15g g creatinine) REFERENCES Global trends on occupational accidents and diseases Accessed August 29,2020 https:/Ax-ww.ilo.org,legac\'english.'oshen'ston_content external_files/fs _st_ -ILO_5_en.pdf p IO CD ting disease through a healthier and safer workspace Accessed August 30 2020 https:/AvwwAvho.inT'publications-detail- redirect/preventing-disease-through-a-hcalthier-and-safcr-workspacc Persons outside the labour foTce: How inactive are they really Accessed August 29 2020 httpsi'/www.ilo.orgAvanspi group&'public.' - dgreports-—$tat'documentS'pubhcation ;wcms_714359.pdf As TRAN D 1, ENGSTROM J, OVRUM p Occupational Poisonings: Lessons Learned from Poison Center Narratives Stđ/iiAnđvMM Journal of Work, Environment A Health 1978:4(3): 185-194 Roundtable on Environmental Health Sciences R Practice B on PH and PH Medicine of The Challenge: Chemicals in Today's Society National Academies Press (VS); 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Yes Moderate C] No 13 Do you use personal protective equipment during working? Regularly [77] 2.Sometimes [77] 3.N0Q What kind of personal propcctivc equipment you use? Gloses |77| Hat Glasses 77] Shoes [777] [7j c Living habits Have you ever smoked tobacco? Yes: o No: «s> ■> clothing [77| Masks 13 Are von smoking currently? No:Q YesrQ IÍ yes bow many cigarettes-day you smoke? Host many years have yon smoked? 20 Appendix chem I cal measuring results ill the working environment Name Ethylbenzene Styrene Total Total Exposed- Of Of No Compan wotkeis (1) workers y Total -w ã* CN ôG