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Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
Journal of Environmental Pathology, Toxicology and Oncology
Импакт фактор: 1.625 5-летний Импакт фактор: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537

Том 39, 2020 Том 38, 2019 Том 37, 2018 Том 36, 2017 Том 35, 2016 Том 34, 2015 Том 33, 2014 Том 32, 2013 Том 31, 2012 Том 30, 2011 Том 29, 2010 Том 28, 2009 Том 27, 2008 Том 26, 2007 Том 25, 2006 Том 24, 2005 Том 23, 2004 Том 22, 2003 Том 21, 2002 Том 20, 2001

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019026470
pages 253-270

Oxidative Stress Parameters, Selenium Levels, DNA Damage, and Phthalate Levels in Plastic Workers

Gulru Gurdemir
Department of Toxicology, Faculty of Pharmacy, Hacettepe University Ankara, Turkey; Turkish Medicines and Medical Devices Agency, Ankara, Turkey
Pinar Erkekoglu
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey
Aylin Balci
Department of Toxicology, Faculty of Pharmacy, Hacettepe University Ankara, Turkey
Unzile Sur
Department of Toxicology, Faculty of Pharmacy, Hacettepe University Ankara, Turkey; Department of Toxicology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
Gizem Ozkemahli
Department of Toxicology, Faculty of Pharmacy, Hacettepe University Ankara, Turkey; Department of Toxicology, Faculty of Pharmacy, Erzincan University, Erzincan, Turkey
Engin Tutkun
Department of Public Health, Bozok University, Yozgat, Turkey
Hinc Yilmaz
Department of Public Health, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey
Ali Asci
Department of Toxicology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
Belma Kocer-Gumusel
Department of Toxicology, Faculty of Pharmacy, Lokman Hekim University Ankara, Turkey

Краткое описание

Di(2-ethylhexyl)phthalate (DEHP) is the most widely used phthalate. DEHP is highly used in PVC floorings and PVC windows and carpeting. The objective of this study was to determine sex hormone levels, oxidative stress parameters, selenium levels, DNA damage, and phthalate levels in plastics workers (n = 24, age = 20-58 years) working in the production of rubber mechanical goods and exposed to DEHP in workplace. The control group (n = 29, age = 25-54, all male) was selected from age-matched healthy adults. Antioxidant parameters and DNA damage were determined by spectrophotometry. Selenium levels were determined by atomic absorption spectroscopy. Plasma hormone levels were measured by chemiluminescence microparticle immunoassay. Plasma phthalate levels were determined by high-pressure liquid chromatography. Plastic workers had lower serum testosterone and free T4 levels and higher follicle-stimulating hormone levels vs. controls. Liver enzyme activities were markedly higher in workers vs. controls. There were also increases in plasma glutathione peroxidase levels and marked decreases in plasma selenium and erythrocyte total glutathione levels in plastics workers (P < 0.05 vs. control). Plasma 8-hydroxy-2'-deoxyguanosine levels were 14-fold higher in plastics workers than in controls. Plasma DEHP and mono(2-ethylhexyl)phthalate were also markedly higher in workers vs. controls. The results of this study show that occupational exposure to DEHP may lead to disturbances in sex hormones, increased liver problems, higher oxidative stress and DNA damage levels, and lower trace element concentrations in workers. More comprehensive and mechanistic studies with higher numbers of subjects are needed to show the unwanted effects of occupational exposure to DEHP.


  1. Wormuth M, Scheringer M, Vollenweider M, Hungerbuhler K. What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal. 2006;26:803e24.

  2. Ticker JA, Schettler T, Guidotti T, McCally M, Rossi M. Health risks posed by use of di-ethylhexyl phthalate, DEHP, in PVC medical devices, a critical review. Am J Ind Med. 2001;39:100e11.

  3. Taiwan Food and Drug Administration. Report. May 28. 2011. Available from: http//www.fda.gov.tw/news.aspx-?newssnZ7641&key_.

  4. Hauser R, Calafat AM. Phthalates and human health. Occup Environ Med. 2005;62:806-18.

  5. Kay VR, Chambers C, Foster WG. Reproductive and developmental effects of phthalate diesters in females. Crit Rev Toxicol. 2013; 43:200-19.

  6. Balbuena P, Campbell J Jr, Clewell HJ 3rd, Clewell RA. Evaluation of a predictive in vitro Leydig cell assay for anti-androgenicity of phthalate esters in the rat. Toxicol in vitro. 2013; 27:1711-18.

  7. Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard AM, Metzdorff SB, Hass U. Low-dose perinatal exposure to di, 2-ethylhexyl. phthalate induces anti-androgenic effects in male rats. Reprod Toxicol. 2010;30: 313-21.

  8. Erkekoglu P, Zeybek ND, Giray B, Asan E, Arnaud J, Hincal F. Reproductive toxicity of di-(2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats. Drug Chem Toxicol. 2011;34:379-89.

  9. Kortenkamp A, Faust M. Combined exposures to anti-androgenic chemicals, steps towards cumulative risk assessment. Int J Androl. 2010;33:463-74.

  10. Svechnikov K, Svechnikova I, Soder O. Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro. Reprod Toxicol. 2008;25:485-90.

  11. IARC (International Agency for Research on Cancer). Some chemicals present in industrial and consumer products, food and drinking-water [monograph]. In: IARC monographs on the evaluation of carcinogenic risks to humans. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://monographs.iarc. fr/ENG/Monographs/vol101/mono101-006.pdf.

  12. Rusyn I, Peters JM, Cunningham ML. Modes of action and species-specific effects of di-, 2-ethylhexyl.phthalate in the liver. Crit Rev Toxicol. 2006;36:459-79.

  13. Erkekoglu P, Rachidi W, Yuzugullu OG, Giray B, Ozturk M, Favier A, Hincal F. Induction of ROS, p53, p21 in DEHP- and MEHP-exposed LNCaP cells-protection by selenium compounds. Food Chem Toxicol. 2011;49:1565-71.

  14. Erkekoglu P, Zeybek ND, Giray BK, Rachidi W, Kizilgun M, Hininger-Favier I, Favier A, Asan E, Hincal F. The effects of di, 2-ethylhexyl.phthalate exposure and selenium nutrition on Sertoli cell vimentin structure and germ-cell apoptosis in rat testis. Arch Environ Contam Toxicol. 2012;62:539-47.

  15. Erkekoglu P, Giray BK, Kizilgun M, Hininger-Favier I, Rachidi W, Roussel AM, Favier A, Hincal F. Thyroidal effects of di(2-ethylhexyl) phthalate in rats of different selenium status. J Environ Pathol Toxicol Oncol. 2012;31:143-53.

  16. Erkekoglu P, Giray BK, Kizilgun M, Rachidi W, Hininger-Favier I, Roussel AM, Favier A, Hincal F. Di, 2-ethylhexyl.phthalate-induced renal oxidative stress in rats and protective effect of selenium. Toxicol Mech Methods. 2012;22:415-23.

  17. Erkekoglu P, Zeybek ND, Giray BK, Rachidi W, Kizilgun M, Hininger-Favier I, Favier A, Asan E, Hincal F. The effects of di, 2-ethylhexyl.phthalate on rat liver in relation to selenium status. Int J Exp Pathol. 2014;95:64-77.

  18. Bulus AD, Asci A, Erkekoglu P, Balci A, Andiran N, Kojer-Gumuel B. The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty. Toxicol Mech Methods. 2016;26:493-500.

  19. Dong R, Zhao S, Zhang H, Chen J, Zhang M, Wang M, Wu M, Li S, Chen B. Sex differences in the association of urinary concentrations of phthalate metabolites with self-reported diabetes and cardiovascular diseases in Shanghai adults. Int J Environ Res Public. 2017;14(6):598. doi: 10.3390/ijerph14060598.

  20. Durmaz E, Asfi A, Erkekoglu P, Akfurin S, Gumu^el BK, Bircan I. Urinary bisphenol A levels in girls with idiopathic central precocious puberty. J Clin Res Pediatr Endocrinol. 2014;6:16-21.

  21. Durmaz E, Ozmert EN, Erkekoglu P, Giray B, Derman O, Hincal F, Yurdakok K. Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents. Int J Hyg Environ Health. 2017; 220:468-77.

  22. Franken C, Lambrechts N, Govarts E, Koppen G, Den Hond E, Ooms D, Voorspoels S, Bruckers L, Loots I, Nelen V, Sioen I, Nawrot TS, Baeyens W, Van Larebeke N, Schoeters G. Phthalate-induced oxidative stress and association with asthma-related airway inflammation in adolescents. Int J Hyg Environ Health. 2017; 220: 468-77.

  23. Kondolot M, Ozmert EN, Asci A, Erkekoglu P, Oztop DB, Gumus H, Kocer-Gumusel B, Yurdakok K. Plasma phthalate and bisphenol A levels and oxidant-antioxidant status in autistic children. Environ Toxicol Pharmacol. 2016;43:149-58.

  24. Stojanoska MM, Milosevic N, Milic N, Abenavoli L.The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders. Endocrine. 2017;55:666-81.

  25. Allsopp M, Santillo D, Johnston P. Hazardous chemicals in carpets. Exeter, UK: Greenpeace Research Laboratories; 2001. Technical Note 01/2001. Available from: http//www.greenpeace.to/publications/carpet.pdf.

  26. Hines CJ, Nilsen Hopf NB, Deddens JA, Calafat AM, Silva MJ, Grote AA, Sammons DL. Occupational exposure to diisononyl phthalate, DiNP, in polyvinyl chloride processing operations. Int Arch Occup Environ Health. 2012;85: 317-25.

  27. Pan G, Hanaoka T, Yu L, Na J, Yamano Y, Hara K, Ichiba M, Nakadate T, Kishi R, Wang P, Yin H, Zhang S, Feng Y. Associations between hazard indices of di-n-butyl-phthalate and di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men. Int J Androl. 2011;34:e397-e406.

  28. Ansari KN. The free radicals-the hidden culprits-an update. Indian J Med Sci. 1997;51: 319-36.

  29. Gutteridge JM, Halliwell B. Free radicals and antioxi-dants in the year 2000. A historical look to the future. Ann NY Acad Sci. 2000;899:136-47.

  30. Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans. 2007;35:1147-50.

  31. Halliwell B. Free radicals, proteins and DNA, oxidative damage versus redox regulation. Biochem Soc Trans. 1996;24:1023-27.

  32. Hayes JD, McLellan LI. Glutathione and glutathi-one-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 1999;31:273-300.

  33. Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, Inoue K, Nakazawa H, Tsugane S, Takahashi K. Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate, DBP and di-2-ethylhexyl phthalate, DEHP, a cross-sectional study in China. Environ Health Perspect. 2006;114: 1643-8.

  34. Wang Q, Wang L, Chen X, Rao KM, Lu SY, Ma ST, Jiang P, Zheng D, Xu SQ, Zheng HY, Wang JS, Yu ZQ, Zhang R, Tao Y, Yuan J. Increased urinary 8-hydroxy-2'-deox- yguanosine levels in workers exposed to di-, 2-ethyl-hexyl.phthalate in a waste plastic recycling site in China. Environ Sci Pollut Res Int. 2011;18:987-96.

  35. Fong JP, Lee FJ, Lu IS, Uang SN, Lee CC. Relationship between urinary concentrations of di(2-ethylhexyl. phthalate, DEHP, metabolites and reproductive hormones in polyvinyl chloride production workers. Occup Environ Med. 2015;72:346-53.

  36. Huang LP, Lee CC, Fan JP, Kuo PH, Shih TS, Hsu PC. Urinary metabolites of di,2-ethylhexyl.phthalate relation to sperm motility, reactive oxygen species generation, and apoptosis in polyvinyl chloride workers. Int Arch Occup Environ Health. 2014;87:635-46.

  37. Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease, from molecular mechanisms to therapeutic opportunities. Antioxid Redox 54. Signal. 2011;15:1957-97.

  38. Takahashi K, Cohen HJ. Selenium-dependent glutathione peroxidase protein and activity, immunological investigations on cellular and plasma enzymes. Blood. 1986;68:640-5.

  39. Mustacich D, Powis G. Thioredoxin reductase. Biochem 56. J. 2000;346(Pt 1):1-8.

  40. Holmgren A. Thioredoxin structure and mechanism, conformational changes on oxidation of the active-site sulfhydryls to a disulfide. Structure. 1995;3:239-43.

  41. Fukai T, Ushio-Fukai M. Superoxide dismutases, role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011;15: 1583-606.

  42. Zamocky M, Furtmuller PG, Obinger C. Evolution of catalases from bacteria to humans. Antioxid Redox Signal. 2008;10:1527-48.

  43. Lemire J, Alhasawi A, Appanna VP, Tharmalingam S, Appanna VD. Metabolic defense against oxidative stress, the road less travelledso far. J Appl Microbiol. 2017 0ct;123(4):798-809. doi: 10.1111/jam.13509.

  44. Ayala A, Munoz MF, Arguelles S. Lipid peroxidation, production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438.

  45. Fairbanks V, Klee GG. Biochemical aspects of hematology. In: Tietz NW, editor. Textbook of clinical chemistry. Philadelphia: W.B. Saunders; 1986. p. 1532-4.

  46. Milne GL, Yin H, Morrow JD. Human biochemistry of the isoprostane pathway. J Biol Chem. 2008;283:15533-7.

  47. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2' -deoxyguanosine (8-OHdG), a critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009;27:120-39.

  48. Baltaci AK, Mogulkoc R, Akil M, Bicer M. Review: selenium-its metabolism and relation to exercise. Pak J Pharm Sci. 2016;29:1719-25.

  49. Kirkbright GE. Atomic absorption spectroscopy. In: Elemental analysis of biological materials, current problems and techniques with special reference to trace elements. Vienna Technical Report Series 197. Vienna: International Atomic Energy Agency; 1980. pp 141-65.

  50. Paris I, Ruggieri F, Mazzeo P, Carlucci G. Simultaneous determination of dimethylhexyl phthalate and mono ethyhlhexyl phthalate in human plasma by HPLC. Anal Lett. 2003;36:2649-58.

  51. Blass CR. PVC as a biomedical polymer-plasticizer and stabilizer toxicity. Med Device Technol. 1992;3:32-40.

  52. Bowman JD, Choudhury M. Phthalates in neonatal health, friend or foe? J Dev Orig Health Dis. 2016;7:652-64.

  53. Shea KM, American Academy of Pediatrics Committee on Environmental Health. Pediatric exposure and potential toxicity of phthalate plasticizers. Pediatrics. 2003;111:1467-74.

  54. Skinner MK. Endocrine disruptors in 2015, epigenetic transgenerational inheritance. Nat Rev Endocrinol. 2016;12: 68-70.

  55. Wang W, Xu X, Fan CQ. Health hazard assessment of occupationally di-2-ethylhexyl.phthalate-exposed workers in China. Chemosphere. 2015;120: 37-44.

  56. Song Y, Chou EL, Baecker A, You NC, Song Y, Sun Q, Liu S. Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits. A systematic review and meta-analysis. J Diabetes. 2016;8:516-32.

  57. Fong JP, Lee FJ, Lu IS, Uang SN, Lee CC. Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate, DEHP, for PVC production workers, using personal air sampling and urinary metabolite monitoring. Int J Hyg Environ Health. 2014;217:102-9.

  58. Grasso P, Heindel JJ, Powell CJ, Reichert LE Jr. Effects of mono(2-ethylhexyl) phthalate, a testicular toxicant, on follicle-stimulating hormone binding to membranes from cultured rat Sertoli cells. Biol Reprod. 1993;48:454-9.

  59. Agarwal DK, Maronpot RR, Lamb JC 4th, Kluwe WM. Adverse effects of butyl benzyl phthalate on the reproductive and hematopoietic systems of male rats. Toxicology. 1985;35:189-206.

  60. Gaudin R, Marsan P, Ndaw S, Robert A, Ducos P. Biological monitoring of exposure to di,2-ethylhexyl.phthalate in six French factories, a field study. Int Arch Occup Environ Health. 2011;84: 523-31.

  61. Kasai H. What causes human cancer? Approaches from the chemistry of DNA damage. Genes Environ. 2016;38:19.

  62. Hines CJ, Nilsen HopfNB, Deddens JA, Calafat AM, Silva MJ, Grote AA, Sammons DL. Urinary phthalate metabolite concentrations among workers in selected industries, a pilot biomonitoring study. Ann Occup Hyg. 2009;53: 1-17.

  63. Poulsen HE, Nadal LL, Broedbaek K, Nielsen PE, Weimann A. Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochim Biophys Acta. 2014;1840:801-8.

  64. Singh S, Li SS. Epigenetic effects of environmental chemicals bisphenol A and phthalates. Int J Mol Sci. 2012;13:10143-53.

  65. Rusyn I, Corton JC. Mechanistic considerations for human relevance of cancer hazard of di,2-ethylhexyl. phthalate. Mutat Res. 2012;750:141-58.

  66. Erkekoglu P, Kocer Giray B. Unpredictable effects of chemical mixtures on liver in health and disease. J Liver Dis Transplant. 2012;1:1.

  67. Hu GX, Lian QQ, Ge RS, Hardy DO, Li XK. Phthalate-induced testicular dysgenesis syndrome, Leydig cell influence. Trends Endocrinol Metab. 2009;20: 139-40.

  68. Ohlson CG, Hardell L. Testicular cancer and occupational exposures with a focus on xenoestrogens in polyvinyl chloride plastics. Chemosphere. 2000;40: 1277-82.

  69. Erkekoglu P, Rachidi W, De Rosa V, Giray B, Favier A, Hincal F. Protective effect of selenium supplementation on the genotoxicity of di,2-ethylhexyl.phthalate and mono,2-ethylhexyl.phthalate treatment in LNCaP cells. Free Radic Biol Med. 2010;49:559-66.

  70. Erkekoglu P, Rachidi W, Yuzugullu OG, Giray B, Favier A, Ozturk M, Hincal F. Evaluation of cytotoxicity and oxidative DNA damaging effects of di-(2-ethylhexyl) phthalate, DEHP and mono-(2-ethylhexyl-phthalate), MEHP on MA-10 Ley dig cells and protection by selenium. Toxicol Appl Pharmacol. 2010;248:52-62.

  71. Garberg P, Hogberg J. Selenium metabolism in isolated hepatocytes, inhibition of incorporation in proteins by mono,2-ethylhexyl.phthalate, a metabolite of the peroxisome proliferator di,2-ethylhexyl.phthalate. Carcinogenesis. 1991;12:7-12.

  72. Stefanowicz FA, Talwar D, O'Reilly DS, Dickinson N, Atkinson J, Hursthouse AS, Rankin J, Duncan A. Erythrocyte selenium concentration as a marker of selenium status. Clin Nutr. 2013;32: 837-42.

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