暴露六價鉻電鍍業作業勞工之氧化傷害指標評估研究

Study on Biomarkers of Oxidative Stress in Electroplating Workers Exposed to Hexavalent Chromium

潘致弘(Chih-Hong Pan)；方亭予(Ting-Yu Fang)

8-羥基脫氧鳥苷 ； 電鍍工廠 ； 六價鉻 ； 丙二醛 ； 氧化傷害 ； 8-hydroxy-2'-deoxyguanosine ； Electroplating factories ； Hexavalent chromium ； Malondialdehyde ； Oxidative stress

勞動及職業安全衛生研究季刊

31卷1期（2023 / 03 / 20）

53 - 66

繁體中文;英文

本研究針對臺灣地區16家電鍍工廠，調查105名男性勞工暴露於六價鉻所造成DNA氧化傷害及脂質過氧化傷害指標之濃度，並與125位於辦公室作業之控制組勞工進行比較。研究對象皆為無吸菸習慣之男性勞工。研究過程中收集作業環境空氣之個人採集樣本、尿液、頭髮、指甲以及健康問卷，據以量化勞工對於六價鉻、DNA氧化傷害、脂質過氧化以及環境污染物的暴露。結果顯示暴露組勞工六價鉻之幾何平均濃度以及空氣中鉻總濃度皆顯著高於控制組。另外暴露組勞工其尿液、頭髮及指甲中鉻的幾何平均濃度以及尿中的DNA氧化傷害指標8-羥基脫氧鳥苷（8-OHdG）、脂質過氧化指標丙二醛（MDA）的濃度皆高於控制組。當控制了共變項後，六價鉻的每日累積暴露量以及尿中鉻濃度與尿液中8-OHdG濃度有統計上的顯著相關性，當尿中鉻濃度每增加10倍其尿中8-OHdG增加1.73倍。校正共變項後，六價鉻的每日累積暴露濃度、尿中鉻濃度與尿中MDA濃度有統計上顯著相關，而當尿中鉻濃度增加10倍其尿中MDA濃度增加1.45倍。爰此電鍍勞工會因為暴露六價鉻而導致DNA氧化傷害以及脂質過氧化傷害。

This study evaluates levels of biomarkers of oxidative DNA damage and lipid peroxidation in 105 male workers at 16 electroplating companies who had been exposed to hexavalent chromium (Cr(VI)). The study participants were 230 non-smoking male workers, comprising 105 electroplating workers who had been exposed to chromium and 125 control subjects who performed office tasks. Personal air samples, spot urine samples, hair samples, fingernail samples and questionnaires were used to quantify exposure to Cr(VI), oxidative DNA damage, lipid peroxidation, and environmental pollutants. Both the geometric mean personal concentrations of Cr(VI) of the Cr-exposed workers and the total Cr concentrations in the air to which they were exposed significantly exceeded those for the control subjects. The geometric mean concentrations of Cr in urine, hair and fingernails, and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) levels in the Cr(VI) exposed workers exceeded those in the control subjects. Daily cumulative Cr(VI) exposure and urinary Cr were significantly correlated with urinary 8-OHdG levels following adjustments for covariates. A ten-fold increase in urinary Cr level was associated with a 1.73-fold increase in urinary 8-OHdG level. Daily cumulative Cr(VI) exposure and urinary Cr level were significantly correlated with urinary MDA level following adjustments for covariates. A ten-fold increase in urinary Cr was associated with a 1.45-fold increase in urinary MDA. Exposure to Cr(VI) increased oxidative DNA injury and the oxidative deterioration of lipids in electroplating workers.

1. (1985).Standard Methods for the Examination of Water and Waste Water.Washington, DC:American Public Health Association.
2. (1990).International Agency for Research on Cancer IARC Monographs on the Evaluation of Carcinogenic Risk to Humans. Vol. 49. Chromium, Nickel and Welding.Lyon, France:IARC.
3. Abdulrahman, FI,Akan, JC,Chellube, ZM,Waziri, M(2012).Levels of heavy metals in human hair and nail samples from Maiduguri Metropolis, Borno State, Nigeria.World Environ,2,81-89.
4. Agency for Toxic Substances and Disease Registry. Case studies in environmental medicine. Chromium toxicity. ATSDR. Course: WB 1466. 2011. Available at http://www.atsdr.cdc.gov/csem/chromium/docs/chromium.pdf
5. Ault, K.(2012).Multiple Imputation for Ordinal Variables: A Comparison of SUDAAN PROC IMPUTE and SAS PROC MI.20th Annual SouthEast SAS Users Group (SESUG) Conference,Seattle, Washington:
6. Bartsch, H(2000).Studies on biomarkers in cancer etiology and prevention: a summary and challenge of 20 years of interdisciplinary research.Mutat Res,462,255-279.
7. Beckman, KB,Ames, BN(1999).Endogenous oxidative damage of mtDNA.Mutat Res,424,51-58.
8. Caglieri, A,Goldoni, M,Acampa, O,Andreoli, R,Vettori, MV,Corradi, M(2006).The effect of inhaled chromium on different exhaled breath condensate biomarkers among chrome-plating workers.Environ Health Perspect,114,542-546.
9. Caglieri, A,Goldoni, M,De Palma, G,Mozzoni, P,Gemma, S,Vichi, S(2008).Exposure to low levels of hexavalent chromium: target doses and comparative effects on two human pulmonary cell lines.Acta Biomed,79,104-115.
10. Chance, B,Sies, H,Boveris, A(1979).Hydroperoxide metabolism in mammalian organs.Physiol Rev,59,527-605.
11. Chao, MR,Wang, CJ,Wu, MT,Pan, CH,Kuo, CY,Yang, HJ(2008).Repeated measurements of urinary methylated/oxidative DNA lesions, acute toxicity, and mutagenicity in coke oven workers.Cancer Epidemiol Biomarkers Prev,17,3381-3389.
12. Dayan, AD,Paine, AJ(2001).Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000.Hum Exp Toxicol,20,439-451.
13. Delatour, T,Douki, T,Gasparutto, D,Brochier, MC,Cadet, J(1998).A novel vicinal lesion obtained from the oxidative photosensitization of TpdG: characterization and mechanistic aspects.Chem Res Toxicol,11,1005-1013.
14. Erhola, M,Toyokuni, S,Okada, K,Tanaka, T,Hiai, H,Ochi, H(1997).Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8-hydroxy-2' deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment.FEBS Lett,409,287-291.
15. Fowler, JF, Jr,Kauffman, CL,Marks, JG, Jr,Proctor, DM,Fredrick, MM,Otani, JM(1999).An environmental hazard assessment of low-level dermal exposure to hexavalent chromium in solution among chromium-sensitized volunteers.J Occup Environ Med,41,150-160.
16. García-Niño, WR,Zatarain-Barrón, ZL,Hernández-Pando, R,Vega-García, CC,Tapia, E,Pedraza-Chaverri, J(2015).Oxidative stress markers and histoLogical analysis in diverse organs from rats treated with a hepatotoxic dose of Cr(VI): effect of curcumin.Biol Trace Elem Res,167,130-145.
17. Gatto, NM,Kelsh, MA,Mai, DH,Suh, M,Proctor, DM(2010).Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: a meta-analysis.Cancer Epidemiol,34,388-399.
18. Gil, HW,Seok, SJ,Jeong, DS,Yang, JO,Lee, EY,Hong, SY(2010).Plasma level of malondialdehyde in the cases of acute paraquat intoxication.Clin Toxicol,48,149-152.
19. Goulart, M,Batoréu, MC,Rodrigues, AS,Laires, A,Rueff, J(2005).Lipoperoxidation products and thiol antioxidants in chromium exposed workers.Mutagenesis,20,311-315.
20. Gray, K,Kumar, S,Figg, N,Harrison, J,Baker, L,Mercer, J(2015).Effects of DNA damage in smooth muscle cells in atherosclerosis.Circ Res,116,816-826.
21. Guichardant, M,Valette-Talbi, L,Cavadini, C,Crozier, G,Berger, M(1994).Malondialdehyde measurement in urine.J Chromatogr,655,112-116.
22. Halliwell, B(1989).Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis.Br J Exp Pathol,70,737-757.
23. Halliwell, B(1999).Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition.Mutat Res,443,37-52.
24. Health Canada(2010).Report on Human Biomonitoring of environmental chemicals in Canada. Results of the Canadian health measures survet cycle 1 (2007-2009).
25. Holvoet, P,Collen, D(1998).Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis.Atherosclerosis,137(Suppl),S33-S38.
26. Hu, CW,Cooke, MS,Tsai, YH,Chao, MR(2015).8-Oxo-7,8-dihydroguanine and 8-oxo-7,8-di-hydro-2' -deoxyguanosine concentrations in various human body fluids: implications for their measurement and interpretation.Arch Toxicol,89,201-210.
27. Huang, YL,Chen, CY,Sheu, JY,Chuang, IC,Pan, JH,Lin, TH(1999).Lipid peroxidation in workers exposed to hexavalent chromium.J Toxicol Environ Health A,56,235-247.
28. Huang, YL,Chuang, IC,Pan, CH,Hsiech, C,Shi, TS,Lin, TH(2000).Determination of chromium in whole blood and urine by graphite furnace AAS.Atom Spect,21,10-16.
29. Humad, S,Zarling, E,Clapper, M,Skosey, JL(1988).Breath pentane excretion as a marker of disease activity in rheumatoid arthritis.Free Radic Res Commun,5,101-106.
30. Kasai, H,Crain, PF,Kuchino, Y,Nishimura, S,Ootsuyama, A,Tanooka, H(1986).Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair.Carcinogenesis,7,849-851.
31. Kerger, BD,Paustenbach, DJ,Corbett, GE,Finley, BL(1996).Absorption and elimination of trivalent and hexavalent chromium in humans following ingestion of a bolus dose in drinking water.Toxicol Appl Pharmacol,141,145-158.
32. Kosugi, H,Enomoto, H,Ishizuka, Y,Kikugawa, K.(1994).Variations in the level of thiobarbituric acid reactant in health humans under different physiological conditions.Biol Pharm Bull,17,1645-1650.
33. Kumar, A,Kaundal, RK,Iyer, S,Sharma, SS(2007).Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy.Life Sci,80,1236-1244.
34. Kuo, HW,Chang, SF,Wu, KY,Wu, FY(2003).Chromium (VI) induced oxidative damage to DNA: increase of urinary 8-hydroxydeoxyguanosine concentrations (8-OHdG) among electroplating workers.Occup Environ Med,60,590-594.
35. Kuo, HW,Lai, JS,Lin, TI(1997).Nasal septum lesions and lung function in workers exposed to chromic acid in electroplating factories.Int Arch Occup Environ Health,70,272-276.
36. Langård, S,Gundersen, N,Tsalev, DL,Gylseth, B(1978).Whole blood chromium level and chromium excretion in the rat after zinc chromate inhalation.Acta Pharmacol Toxicol,42,142-149.
37. Lupescu, A,Jilani, K,Zelenak, C,Zbidah, M,Qadri, SM,Lang, F(2012).Hexavalent chromium inducederythrocyte membrane phospholipid asymmetry.BioMetals,25,309-318.
38. Misra, M,Alcedo, J,Wetterhahn, KE(1994).Two pathways for chromium(VI)-induced DNA damage in 14 day chick embryos: Cr-DNA binding in liver and 8-oxo-2’-deoxyguanosine in red blood cells.Carcinogenesis,15,2911-2917.
39. O'Brien, TJ,Ceryak, S,Patierno, SR(2003).Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms.Mutat Res,533,33-36.
40. Pan, CH,Chan, CC,Huang, YL,Wu, KY(2008).Urinary 1-hydroxypyrene and malondialdehyde in male workers in Chinese restaurants.Occup Environ Med,65,732-735.
41. Pan, CH,Chan, CC,Wu, KY(2008).Effects on Chinese restaurant workers of exposure to cooking oil fumes: a cautionary note on urinary 8-Hydroxy-2’-Deoxyguanosine.Cancer Epidemiol Biomarkers Prev,17,3351-3357.
42. Parveen, K,Khan, MR,Siddiqui, WA(2009).Pycnogenol prevents potassium dichromate K2Cr2O7-induced oxidative damage and nephrotoxicity in rat.Chem Biol Interact,181,343-350.
43. Pellerin, C,Booker, SM(2000).Reflections on hexavalent chromium: health hazards of an industrial heavyweight.Environ Health Perspect,108,A402-A407.
44. Persoons, R,Arnoux, D,Monssu, T,Culié, O,Roche, G,Duffaud, B(2014).Determinants of occupational exposure to metals by gas metal arc welding and risk management measures: a biomonitoring study.Toxicol Lett,231,135-141.
45. Pesch Kendzia, B,Hauptmann, K,Van Gelder, R,Stamm, R,Hahn, JU(2015).Airborne exposure to inhalable hexavalent chromium in welders and other occupations: estimates from the German MEGA database.Int J Hyg Environ Health,218,500-506.
46. Pilger, A,Germadnik, D,Riedel, K,MegerKossien, I,Scherer, G,Rüdiger, HW(2001).Longitudinal study of urinary 8-hydroxy-2' -deoxyguanosine excretion in healthy adults.Free Radic Res,35,273-280.
47. Proctor, DM,Suh, M,Campleman, SL,Thompson, CM(2014).Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposure.Toxicology,325,160-179.
48. Schneider, BC,Constant, SL,Patierno, SR,Jurjus, RA,Ceryak, SM(2012).Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology.Toxicol Appl Pharmacol,259,38-44.
49. Shi, X,Chiu, A,Chen, CT,Halliwell, B,Castranova, V,Vallyathan, V(1999).Reduction of chromium(VI) and its relationship to carcinogenesis.J Toxicol Environ Health B Crit Rev,2,87-104.
50. Slade, PG,Hailer, MK,Martin, BD,Sugden, KD(2005).Guanine-Specific Oxidation of Double-Stranded DNA by Cr(VI) and Ascorbic Acid Forms Spiroiminodihydantoin and 8-Oxo-2' -deoxyguanosin.Chem Res Toxicol,18,1140-1149.
51. Soudani, N,Troudi, A,Bouaziz, H,Ben Amara, I,Boudawara, T,Zeghal, N(2011).Cardioprotective effects of selenium on chromium(VI)-induced toxicity in female rat.Ecotoxicol Environ Saf,74,513-520.
52. Sudha, S,Kripa, SK,Shibily, P,Joseph, S,Balachandar, V(2011).Biomonitoring of genotoxic effects among shielded manual metal arc welders.Asian Pac J Cancer Prev,12,1041-1044.
53. Sukumar, A,Subramanian, R(2003).Elements in the hair of non-mining workers of a lignite open mine in Neyveli.Ind Health,41,63-68.
54. Sun, L,Wang, X,Yao, H,Li, W,Son, YO,Luo, J(2012).Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells.J Environ Pathol Toxicol Oncol,31,95-107.
55. Takeuchi, T,Matsugo, S,Morimoto, K(1997).Mutagenicity of oxidative DNA damage in Chinese hamster V79 cells.Carcinogenesis,18,2051-2055.
56. Thompson, CM,Kirman, CR,Proctor, DM,Haws, LC,Suh, M,Hays, SM(2014).A chronic oral reference dose for hexavalent chromium-induced intestinal cancer.J Appl Toxicol,34,525-536.
57. Toraason, M,Hayden, C,Marlow, D,Rinehart, R,Mathias, P,Werren, D(2001).DNA strand breaks, oxidative damage, and 1-OH pyrene in roofers with coal-tar pitch dust and/or asphalt fume exposure.Int Arch Occup Environ Health,74,396-2404.
58. Vaglenov, A,Nosko, M,Georgieva, R,Carbonell, E,Creus, A,Marcos, R(1999).Genotoxicity and radioresistance4 in electroplating workers exposed to chromium.Mutat Res,446,23-34.
59. Vincent, R,Gillet, M,Goutet, P,Guichard, C,Hédouin-Langlet, C,Frocaut, AM(2015).Occupational exposure to chrome VI compounds in French companies: results of a national campaign to measure exposure (2010-2013).Ann Occup Hyg,59,41-51.
60. Weimann, A,Belling, D,Poulsen, HE(2002).Quantification of 8-oxo-guanine and guanine as the nucleobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry.Nucleic Acids Res,30,E7.
61. Wise, SS,Holmes, AL,Qin, Q,Xie, H,Katsifis, SP,Thompson, WD(2010).Comparative genotoxicity and cytotoxicity of four hexavalent chromium compounds in human bronchial cells.Chem Res Toxicol,23,365-372.
62. Wise, SS,Holmes, AL,Wise, JP, Sr(2008).Hexavalent chromium-induced DNA damage and repair mechanisms.Rev Environ Health,23,39-57.
63. Xie, H,Wise, SS,Holmes, AL,Xu, B,Wakeman, TP,Pelsue, SC(2005).Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells.Mutat Res,586,160-172.
64. Yoshida, R,Ogawa, Y,Mori, I,Nakata, A,Wang, R,Ueno, S(2003).Associations between oxidative stress levels and total duration of engagement in jobs with exposure to fly ash among workers at municipal solid waste incinerators.Mutagenesis,18,533-537.
65. Yuan, Y(2011).Multiple imputation using SAS software.J Stat Softw,45,1-25.
66. Zakaria, ZA,Ahmad, WA,Zakaria, Z,Razali, F,Karim, NA,Sum, MM(2012).Bacterial reduction of Cr(VI) at technical scale--the Malaysian experience.Appl Biochem Biotechnol,167,1641-1652.
67. Zaprianov, Z,Tsalev, D,Georgieva, R,Kaloianova, F,Nikolova, V(1989).New toxicokinetic exposure tests for metals based on atomic absorption analysis of the nails.Probl Khig,14,75-97.
68. Zhang, J,Perry, G,Smith, MA,Robertson, D,Olson, SJ,Graham, DG(1999).Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons.Am J Pathol,154,1423-1429.
69. Zhang, PY,Xu, X,Li, XC(2014).Cardiovascular diseases: oxidative damage and antioxidant protection.Eur Rev Med Pharmacol Sci,18,3091-3096.
70. Zhang, XH,Zhang, X,Wang, XC,Jin, LF,Yang, ZP,Jiang, CX(2011).Chronic occupational exposure to hexavalent chromium causes DNA damage in electroplating workers.BMC Public Health,11,224.