Presence of phthalate esters in intravenous solution evaluated using gas chromatography-mass spectrometry method (original) (raw)

Abstract

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the production of poly-(vinyl) chloride (PVC) materials. It is a reproductive and developmental toxicant in animals and a suspected endocrine modulator in humans. DEHP is not covalently bound within the PVC molecule, which is why migration into a suitable medium can be expected. Since application of infusion solutions is one of the most common medical treatments, the objective of this study was to determine the migration of phthalates from softened PVC storage bags into infusion solution in different time periods within one year from date of production using a gas chromatography-mass spectrometry method. The measured values of DEHP ranged between 0.22 and 14.00 mg l À1 , but the unexpected presence of other phthalate esters was also detected. It was concluded that values obtained in infusion solutions match the reference data and represent a minor risk for the patient. The presence of other phthalate esters leads to the conclusion that the pharmacopeic requirement for polymer cleanness was not fully met. Since phthalate esters are among the most extensively used industrial chemicals and are widely distributed in the environment, special precautions and further monitoring should be conducted to minimize any possible health risks.

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References (47)

  1. Anderson D, Yu TW, Hinçal F. 1999. Effect of some phthalate esters in human cells in the comet assay. Teratog. Carcinog. Mutagen. 19: 275-280; doi: 10.1002/(SICI)1520-6866(1999)19:4<275::AID-TCM4>3.0. CO;2-1.
  2. Arbin A, Östelius J. 1980. Determination by electron-capture gas chroma- tography of mono-and di(2-ethylhexyl) phthalate in intravenous solutions stored in poly(vinyl chloride) bags. J. Chromatogr. A 193: 405-412; doi: 10.1016/S0021-9673(00)87740-7.
  3. Boniol M, Autier P. 2010. Prevalence of main cancer lifestyle risk factors in Europe in 2000. Eur. J. Cancer 46: 2534-2544; doi: 10.1016/j. ejca.2010.07.049.
  4. Choi S, Park SY, Jeong J, Cho E, Phark S, Lee M, Kwak D, Lim JY, Jung WW, Sul D. 2010. Identification of toxicological biomarkers of di(2-ethyl- hexyl) phthalate in proteins secreted by HepG2 cells using proteomic analysis. Proteomics 10: 1831-1846; doi: 10.1002/pmic.200900674.
  5. Corley JH, Needham TE, Sumner ED, Mikael R. 1977. Effect of various fac- tors on the amount of plasticizer in intravenous solution packaged in flexible bags. Am. J. Hosp. Pharm. 34: 259-264.
  6. Council of Europe. 2008. European Pharmacopoeia, 6th edn. Strasbourg. European Directorate for the Quality of Medicines, Council of Europe. 2008. European Pharmacopoeia, General Monograph on Dosage Forms. Chewing Gums, Medicated. 6th edition, Strasbourg, France.
  7. Duty SM, Singh NP, Silva MJ, Barr DB, Brock JW, Ryan L, Herrick RF, Chris- tiani DC, Hauser R. 2003. The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ. Health Perspect. 111: 1164-1169.
  8. EPA. 1990. Method 8061A. Phthalate Esters by Gas Chromatography with Electron Capture Detection (GC/ECD). United States Environmental Protection Agency.
  9. Erkekoğlu P, Rachidi W, De Rosa V, Giray B, Favier A, Hincal F. 2010a. Pro- tective 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. 49: 559-566; doi: 10.1016/j. freeradbiomed.2010.04.038.
  10. Erkekoğlu P, Rachidi W, Yuzugullu OG, Giray B, Favier A, Ozturk M, Hincal F. 2010b. Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethyl- hexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by se- lenium. Toxicol. Appl. Pharmacol. 248: 52-62; doi: 10.1016/j. taap.2010.07.016.
  11. FDA. 2001. Center for Devices and Radiological Health Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical. United States Food and Drug Administration.
  12. Gotay CC. 2010. Cancer prevention: major initiatives and looking into the future. Expert Rev. Pharmacoecon. Outcomes Res. 10: 143-154; doi: 10.1586/erp.10.9.
  13. Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM. 2007. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum. Reprod. 22: 688-695; doi: 10.1093/humrep/del428.
  14. Heudorf U, Mersch-Sundermann V, Angerer J. 2007. Phthalates: toxicol- ogy and exposure. Int. J. Hyg. Environ. Health 210: 623-634; doi: 10.1016/j.ijheh.2007.07.011.
  15. Högberg J, Hanberg A, Berglund M, Skerfving S, Remberger M, Calafat AM, Falk Filipsson A, Jansson B, Johansson N, Appelgren M, Håkansson H. 2008. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ. Health Perspect. 116: 334-339; doi: 10.1289/ ehp.10788
  16. IARC. 1990. Cancer: Causes, Occurrence and Control. IARC Scientific Pub- lication no. 100. International Agency for Research on Cancer.
  17. Jaeger RJ, Rubin RJ. 1972. Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its local- ization in human tissues. New Engl. J. Med. 287: 1114-1148; doi: 10.1016/S0899-9007(97)90963-1.
  18. Jaeger RJ, Rubin RJ. 1973. Extraction, localization, and metabolism of di- 2-ethylhexyl phthalate from PVC plastic medical devices. Environ. Health Perspect. 3: 95-102.
  19. Jenke D. 2002. Extractable/leachable substances from plastic materials used as pharmaceutical product containers/devices. PDA J. Pharm. Sci. Technol. 56: 332-371.
  20. Jensen LE, Jorgen M. 1977. Leaching of plasticizers from polyvinyl chlo- ride bags into stored blood. Arch. Pharm. Chem. (Sci. Edn) 5: 43-49.
  21. Jin M, Dewa Y, Kawai M, Nishimura J, Saegusa Y, Kemmochi S, Harada T, Shibutani M, Mitsumori K. 2009. Induction of liver preneoplastic foci in F344 rats subjected to 28-day oral administration of diheptyl phthalate and its in vivo genotoxic potential. Toxicology 264: 16-25; doi: 10.1016/j.tox.2009.07.006.
  22. Kamrin MA. 2009. Phthalate risks, phthalate regulation, and public health: a review. J. Toxicol. Environ. Health B Crit. Rev. 12: 157-174; doi: 10.1080/10937400902729226.
  23. Kavlock R, Boekelheide K, Chapin R, Cunningham M, Faustman E, Fostre P, Golub M, Henderson R, Hinberg I, Little R, Seed J, Shea K, Tabacova S, Tyl R, Williams P, Zacharewski T. 2002. NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and development toxicity of di(2-ethylhexyl) phthalate. Reprod. Toxicol. 16: 529-653; doi: 10.1016/S0890-6238(02)00032-1.
  24. Khaliq MA, Alam MS, Srivastava SP. 1992. Implications of physico- chemical factors on the migration of phthalate esters from tubing commonly used for oral/nasal feeding. Bull. Environ. Contam. Toxicol. 48: 572-578; doi: 10.1007/BF00199076.
  25. Kleinsasser NH, Wallner BC, Kastenbauer ER, Weissacher H, Harréus UA. 2001. Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells. Teratog. Carcinog. Muta- gen. 21: 189-196; doi: 10.1002/tcm.1007.
  26. Kleinsasser NH, Harréus UA, Kastenbauer ER, Wallner BC, Sassen AW, Staudenmaier R, Rettenmeier AW. 2004. Mono(2-ethylhexyl)phtha- late exhibits genotoxic effects in human lymphocytes and mucosal cells of the upper aerodigestive tract in the comet assay. Toxicol. Lett. 148: 83-90; doi: 10.1016/j.toxlet.2003.12.013.
  27. Koch HM, Drexler H, Angerer J. 2003. An estimation of the daily intake of di(2-ethylhexyl) phthalate (DEHP) and other phthalates in the general population. Int. J. Hyg. Environ. Health 206: 1-7; doi: 10.1078/1438- 4639-00205.
  28. Koch HM, Preuss R, Angerer J. 2006. Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure -an update and latest results. Int. J. Androl. 29: 155-165; doi: 10.1111/j.1365-2605.2005.00607.x.
  29. Labow RS, Tocchi M, Rock G. 1986. Contamination of platelet storage bags by phthalate esters. J. Toxicol. Environ. Health 19: 591-598; doi: 10.1080/15287398609530955.
  30. Meeker JD, Sathyanarayana S, Swan SH. 2009. Phthalates and other additives in plastics: human exposure and associated health outcomes. Phil. Trans. R. Soc. Lond. B Biol. Sci. 364: 2097-2113; doi: 10.1098/rstb.2008.0268.
  31. Miripol J, Stern I. 1977. Decreased accumulation of phthalate plasticizer during storage of blood as packed cells. Transfusion 17: 17-72; doi: 10.1046/j.1537-2995.1977.17177128891.
  32. Nässberger L, Arbin A, Östelius J. 1987. Exposure of patients to phtha- lates from polyvinyl chloride tubes and bags during dialysis. Nephron 45: 286-290; doi: 10.1159/000184165
  33. Oehlmann J, Schulte-Oehlmann U, Kloas W, Jagnytsch O, Lutz I, Kusk KO, Wollenberger L, Santos EM, Paull GC, Van Look KJ, Tyler CR. 2009. A crit- ical analysis of the biological impacts of plasticizers on wildlife. Phil. Trans.
  34. R. Soc. Lond. B Biol. Sci. 364: 2047-2062; doi: 10.1098/rstb.2008.0242. Rivedal E, Mikalsen SO, Sanner T. 2000. Morphological transformation and effect on gap junction intercellular communication in Syrian hamster embryo cells as screening tests for carcinogens devoid of mutagenic activity. Toxicol. in Vitro 14: 185-192; doi: 10.1016/ S0887-2333(00)00006-0.
  35. Roksvaag PO, Smistad G, Waaler T. 1990. The covariation of chemical contamination, particulate matter and turbidity in soft polyvinyl chlo- ride infusion fluid bags. Acta Pharm. Nord. 2: 327-332.
  36. Rubin RJ, Schiffer CA. 1976. Fate in humans of the plasticizer, di-2-ethyl- hexyl phthalate, arising from transfusion of platelets stored in vinyl plastic bags. Transfusion 16: 330-335; doi: 10.1046/j.1537- 2995.1976.16476247053.
  37. Sasakawa S, Mitomi Y. 1978. Di-2-ethylhexylphthalate (DEHP) content of blood or blood components stored in plastic bags. Vox Sang. 34: 81-86; doi: 10.1111/j.1423-0410.1978.tb03727.x.
  38. Schettler T. 2006. Human exposure to phthalates via consumer products. Int. J. Androl. 29: 134-139; doi: 10.1111/j.1365-2605.2005.00567.x.
  39. Seed JL. 1982. Mutagenic activity of phthalate esters in bacterial liquid suspension assays. Environ. Health Perspec. 45: 111-114.
  40. Smistad G, Waaler T, Roksvaag PO. 1989. The influence of product factors on the migration in soft polyvinyl chloride infusion fluid bags. Acta Pharm. Nord. 1: 313-320.
  41. Tennant RW, Ashby J. 1991. Classification according to chemical struc- ture, mutagenicity to Salmonella and level of carcinogenicity of a further 39 chemicals tested for carcinogenicity by the U.S. National Toxicology Program. Mutat. Res. 257: 209-227; doi: 10.1016/0165- 1110(91)90002-D.
  42. Thomas JA, Northup SJ. 1982. Toxicity and metabolism of monoethyl- hexyl phthalate and diethylhexyl phthalate: a survey of recent litera- ture. J. Toxicol. Environ. Health 9: 141-152; doi: 10.1080/ 15287398209530149.
  43. Tickner JA, Schettler T, Guidotti T, McCally M, Rossi M. 2001. Health risks posed by use of di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am. J. Ind. Med. 39: 100-111; doi: 10.1002/ 1097-0274(200101)39:1<100::AID-AJIM10>3.0.CO;2-Q.
  44. Ulsaker GA, Hoem RM. 1978. Determination by gas chromatography-sin- gle-ion monitoring mass spectrometry of phthalate contaminants in intravenous solutions stored in PVC bags. Analyst 103: 1080-1083; doi: 10.1039/AN9780301080.
  45. Wahl HG, Hoffmann A, Häring HU, Liebich HM. 1999. Identification of plasticizers in medical products by a combined direct thermodesorp- tion-cooled injection system and gas chromatography-mass spec- trometry. J. Chromatogr. A 847: 1-7; doi: 10.1016/S0021-9673(99) 00138-7.
  46. Woodward KN. 1988. Phthalate Esters: Toxicity and Metabolism, Vol. 1. CRC Press: Boca Raton, FL.
  47. Zeiger E, Haworth S, Speck W, Mortelmans K. 1982. Phthalate ester testing in the National Toxicology Program's environmental muta- genesis test development program. Environ. Health Perspect. 45: 99-101.