European Journal of Pediatrics

, Volume 147, Issue 1, pp 41–46 | Cite as

Di-(2-ethylhexyl)-phthalate as plasticizer in PVC respiratory tubing systems: indications of hazardous effects on pulmonary function in mechanically ventilated, preterm infants

  • B. Roth
  • P. Herkenrath
  • H. -J. Lehmann
  • H. -D. Ohles
  • H. J. Hömig
  • G. Benz-Bohm
  • J. Kreuder
  • A. Younossi-Hartenstein
Original Investigations


Several PVC medical devices contain the plasticizer Di-(2-ethylhexyl)-phthalate (DEHP) in high concentration. Taken systemically DEHP only has minor toxic effects in the human organism. In three preterm infants artifically ventilated with PVC respiratory tubes unusual lung disorders resembling those observed in hyaline membrane disease, verified both clinically and radiologically, were observed during the fourth week of life. It was assumed that these lung disorders were causally related to the exposure to high doses of DEHP, which was released from the walls of the respiratory tubes. DEHP was found in the lung tissue of one patient who died of pneumothorax soon after birth after being artifically ventilated. It is strongly recommended that for disposable PVC respiratory devices the plasticizer DEHP should be used with more restrictions.

Key words

Premature infant Artificial respiration Polyvinyls Phthalic acids Respiratory distress syndrome 









gas chromatography — mass spectrometry


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  1. 1.
    Agarwal DK, Eustis S, Lamb JC, Kluwe WM (1983) Relationship between zinc and di-(2-ethylhexyl)-phthalate — induced testicular atrophy in adults rats. Pharmacologist 25:226–232Google Scholar
  2. 2.
    Albro PW, Thomas R, Fishbein L (1973) Metabolism of diethylhexyl phthalate by rats-isolation and characterization of the urinary metabolites. J Chromatogr 76:231–330Google Scholar
  3. 3.
    Albro PW, Corbett JT, Schroeder JL, Jordan S, Metthews HB (1982) Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect 45:19–25Google Scholar
  4. 4.
    Autian J (1973) Toxicity and health threats of phthalate esters: review of the literature. Environ Health Perspect 4:3–26Google Scholar
  5. 5.
    Baader EW (1961–1963) Handbuch der gesamten Arbeitsmedizin, vol II/1. Berlin Münster Wien, p 590Google Scholar
  6. 6.
    Baker RW (1978) Diethylhexyl phthalate as a factor in blood transfusion and hemodialysis. Toxicology 9:319–329Google Scholar
  7. 7.
    Bally MB, Opheim DJ, Shertzer HG (1980) Di-(2-ethylhexyl)-phthalate enhances the release of lysosomal enzymes from alveolar macrophages during phagocytosis. Toxicology 18:49–60Google Scholar
  8. 8.
    Bommer J, Ritz E, Andrassy K (1985) Side effects due to materials used in hemodialysis equipment. Adv Nephrol 14:409–438Google Scholar
  9. 9.
    Braun W (1981) Vergiftungsregister, 3rd edn. Stuttgart, p 151Google Scholar
  10. 10.
    Bruck SD (1982) The need for better plastic materials for disposable medical applications: publish health benefits and industrial developments. Int J Artif Organs 5:85–96Google Scholar
  11. 11.
    Brunetti G, Moscato G (1984) Asma bronchiale da esposizione proffessioinale a dioctilftalato. Descrizione di un caso. Med Lav 75:120–124Google Scholar
  12. 12.
    Butterworth BE, Bermudez E, Smith-Oliver T, Earle L, Cattley R, Martin J, Popp JA, Strom S, Jirtle R, Michalopoulos G (1984) Lack of genotoxic activity of di-(2-ethylhexyl)-phthalate (DEHP) in rat and human hepatocytes. Carcinogenesis 5:1329–1335Google Scholar
  13. 13.
    Curto KA, Thomas JA (1982) Comparative effects of diethylhexyl-phthalate or monoethylhexyl-phthalate on male mouse and rat reporductive organs. Toxicol Appl Pharmacol 62:121–125Google Scholar
  14. 14.
    Daniel JW (1978) Toxicity and metabolism of phthalate esters. Clin Toxicol 13:257–268Google Scholar
  15. 15.
    Editorial (1975) A further hazard of intravenous therapy? Br Med J 3:262Google Scholar
  16. 16.
    Editorial (1975) PVC, plasticizers, and the paediatrician. Lancet I:1172–1173Google Scholar
  17. 17.
    Fishbein L, Albro PW (1972) Chromatographic and biological aspects of the phthalate esters. J Chromatogr 70:365–412Google Scholar
  18. 18.
    Fratantoni JC (1982) Safety of DEHP: role of the bureau of biologics. Environ Health Perspect 45:143–144Google Scholar
  19. 19.
    Griffiths WC, Camara P, Lerner KS (1985) Bis-(2-ethylhexyl)-phthalate, an ubiquitos environmental contaminand. Ann Clin Lab Sci 15:140–151Google Scholar
  20. 20.
    Guess WL (1978) Safety evaluation of medical plastics. Clin Toxicol 12:77–95Google Scholar
  21. 21.
    Haughey DB, Breutzmann D, Hemphill G, Collins A, Keshaviak P (1984) Kinetics of diethylhexyl phthalate released into blood perfusates from PVC hemodialysis tubings. Kidney Int 285:563Google Scholar
  22. 22.
    Hillmann LS, Goodwin SL, Sherman WR (1975) Identification and measurement of plasticizer in neonatal tissue after umbilical catheters and blood products. N Engl J Med 292:381–386Google Scholar
  23. 23.
    Ishikawa Y, Honda K, Sasakawa S, Hatada K, Kobayashi H (1983) Prevention of leakage of di-(2-ethylhexyl)-phthalate from blood bags by glow discharge treatment and its effect on aggregability of stored platelets. Vox Sang 45:68–76Google Scholar
  24. 24.
    Jacobson MS, Kevy SV, Grand RJ (1977) Effects of plasticizer leached from polyvinyl chloride on the subhuman primate: a consequence of chronic transfusion therapy. J Lab Clin Med 89: 1066–1079Google Scholar
  25. 25.
    Jaeger RJ, Rubin RJ (1972) Migration of a phthalate ester plasticizer from polyvinyl chloride blood bags into stored human blood and its localization in human tissue. N Engl J Med 287:1114–1118Google Scholar
  26. 26.
    Kaul AF, Souney PF, Osathanondh R (1982) A review of possible toxicity of di-2-ethylhexyl-phthalate (DEHP) in plastic intravenous container: effects on reproduction. Drug Intell Clin Pharm 16:689–692Google Scholar
  27. 27.
    Kerkay J, Nakamoto S (1979) Plasticizer and the uremic patient. Int J Artif Organs 2:107–109Google Scholar
  28. 28.
    Klos M, Nowicki P, Sobecko B (1980) The effect of plasticizers of plastic material bags on biochemical and morphological changes of morphotic blood elements. Pol J Pharmacol Pharm 32:103–107Google Scholar
  29. 29.
    Lawrence WH, Malik M, Turner JE, Singh AR, Autian J (1975) A toxicological investigation of some acute, short-term, and chronic effects of administration of di-2-ethylhexyl-phthalate (DEHP) and other phthalate esters. Environ Res 9:1–11Google Scholar
  30. 30.
    Nedick RL (1975) Polyvinyl chloride containers. Nt Med J 81:534–535Google Scholar
  31. 31.
    Nowicki P, Klos M (1980) Certain problems of toxicity assessment of plastic materials used for blood preservation and preparation. Pol J Pharmacol Pharma 32:77–84Google Scholar
  32. 32.
    Oishi S, Hiraga K (1980) Testicular atrophy induced by phthalic acid esters: effect on testosterone and zinc concentrations. Toxicol Appl Pharmacol 53:35–41Google Scholar
  33. 33.
    Oishi S, Hiraga K (1980) Testicular atrophy induced by phthalic acid monoesters: effects of zinc and testosteron concentrations. Toxicology 15:197–202Google Scholar
  34. 34.
    Parmar D, Srivastava SP, Seth PK (1986) Effect of di-(2-ethylhexyl)-phthalate (DEHP) on spermatogenesis in adult rats. Toxicology 42:47–55Google Scholar
  35. 35.
    Peck CC, Albro PW (1982) Toxic potential of the plasticizer di-(2-ethylhexyl)-phthalate in the context of its disposition and metabolism in primates and man. Environ Health Perspect 45:11–17Google Scholar
  36. 36.
    Petrick RJ, Loucas SP, Cohl JK, Mehl B (1977), Review of current knowledge of plastic intravenous fluid containers. Am J Hosp Pharm 34:357–362Google Scholar
  37. 37.
    Rubin RJ (1976) Metabolism and acute lung toxicity of solubilized di-(2-ethylhexyl)-phthalate (DEHP) in rats. In: Proceedings of the 6th International Congress on Pharmacology Pergamon Press, Oxford, p 205Google Scholar
  38. 38.
    Rubin RJ, Schiffer CA (1976) Fate in humans of the plasticizer, di-2-ethylhexyl-phthalate, arising from transfusion of platelets stored in vinyl plastic bags. Transfusion 16:330–335Google Scholar
  39. 39.
    Schmid P, Schlatter CH (1985) Excretion and metabolism of di-(2-ethylhexyl)-phthalate in man. Xenobiotica 15:251–256Google Scholar
  40. 40.
    Schulz CO, Rubin RJ (1973) Distribution, metabolism and excretion of di-2-ethylhexyl-phthalate in the rat. Environ Health Perspect 3:123–129Google Scholar
  41. 41.
    Schulz CO, Rubin RJ, Hutchins GM (1975) Acute lung toxicity and sudden death in rats following the intravenous administration of the platicizer di-(2-ethylhexyl)-phthalate, solubilized with tween surfactant. Toxicol Appl Pharmacol 33:514–525Google Scholar
  42. 42.
    Seemann J, Martens HL Woelcke U (1976) Di-2-ethylhexyl-phthalat in PVC-verpackten Plasmaersatzlösungen auf Dextranbasis. Bestimmung und toxikologische Bewertung. Münch Med Wochenschr 118:923–924Google Scholar
  43. 43.
    Senico RM, Tegner H, Kuhn L, Ohlsson K, Starcker BL, Pierce IA (1977) The induction of pulmonary emphysema with human leukocyte elastase. Am Rev Resp Dis 116:469–475Google Scholar
  44. 44.
    Shaffer CB, Carpenter CP, Smyth HG (1945) Acute and subacute toxicity of di-(2-ethylhexyl)-phthalate with note upon its metabolism. J Industr Hyg Toxicol 27:130–135Google Scholar
  45. 45.
    Shertzer HG, Bally MB, Opheim DJ (1985) Inhibition of alveolar macrophage killing by di-(2-ethylhexyl)-phthalate. Arch Environ Contam Toxicol 14:605–608Google Scholar
  46. 46.
    Sjøberg POJ, Bondesson U, Sedin EG, Gustaffson IP, (1985) Exposure of newborn infants to plasticizers. Plasma levels of di-(2-ethylhexyl)-phthalate and mono-(2-ethylhexyl)-phthalate during exchange transfusion. Transfusion, 25:424–428Google Scholar
  47. 47.
    Stetson JB, Autian J (1976) Necrotizing enterocolitis and plastic catheters. In: Stern L, Friis-Hansen B, Kildeberg P (eds) Intensive care in the newborn. Masson, New york, pp. 79–98Google Scholar
  48. 48.
    Snyder EL (1979) Non-infectious and non-immunologic complications of blood transfusion. Conn Med 43:206–211Google Scholar
  49. 49.
    Thomas JA, Northup SJ (1982) Toxicity and metabolism of monoethylhexylphthalate and diethylhexylphthalate: a survey of recent literature. J Toxicol Environ Health 9:141–152Google Scholar
  50. 50.
    Thomas JA, Thomas MJ (1984) Biological effects of di-(2-ethylhexyl)-phthalate and other phthalic acid esters. Crit Rev Toxicol 13:283–317Google Scholar
  51. 51.
    Thomas JA, Darby TD, Wallin RF, Garvin PJ, Martin L (1978) A review of the biological effects of di-(2-ethylhexyl)-phthalate. Toxicol Appl Pharmacol 45:1–27Google Scholar
  52. 52.
    Ullmann S (1979) Encyklopädie der technischen Chemie. Toxikologie Phthalsäureester. Disek-octylphthalat, 4th edn, vol 18. Verlag Chemie, Weinheim, pp 539–543Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • B. Roth
    • 3
  • P. Herkenrath
    • 3
  • H. -J. Lehmann
    • 1
  • H. -D. Ohles
    • 2
  • H. J. Hömig
    • 2
  • G. Benz-Bohm
    • 4
  • J. Kreuder
    • 5
  • A. Younossi-Hartenstein
    • 3
  1. 1.Prüfstelle für Medizinische TechnikTÜV RheinlandKölnGermany
  2. 2.Institut für Materialprüfung und ChemieTÜV RheinlandKölnGermany
  3. 3.Universitäts-KinderklinikKölnGermany
  4. 4.Abteilung für RadiologieKölnGermany
  5. 5.Abteilung für PathologieKölnGermany

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