Various plasticizers have been used as softeners for PVC. The plasticizer of choice for PVC medical devices is DEHP.1 The content of DEHP in flexible polymer materials varies widely but is often around 30% -35% (w/w). On the contrary, polyethylene and polypropylene normally do not contain any plasticizers.2-3
Large amounts of DEHP in polymers are building up in:
- End products with long service lives (e.g. building materials)
- Waste remaining in the environment (pieces of polymer)
The International Agency for Research on Cancer, part of the World Health Organization (WHO) classified DEHP as possibly carcinogenic to humans (Group 2B)4, an opinion which has been adopted by many others like the US Department of Health and Human Services.5
Areas of Use of DEHP
DEHP is not known to occur naturally. The worldwide production of DEHP has been increasing over the past several decades. Around 97% of DEHP is used as a plasticizer in polymers, mainly PVC.
Exposure to DEHP varies widely, and is dependent on:
- Medical procedure
- Lipophilicity, or ability of a chemical compound to dissolve in lipids, of the fluid that comes into contact with the medical devices
- PVC surface size
- Flow rate
- Contact time 6-10
Why are DEHP containing medical devices of concern?
On a weight basis, DEHP may constitute 30-40% of a typical blood bag.12 Polyethylene linings of PVC articles (e.g. tubings) do not seem to substantially prevent the release of DEHP.13-14
Especially with IV fluid containers made of PVC and softened with DEHP, there are several areas of concern:
- Leaching is the release of DEHP from PVC containers into the medication contained in the IV bag. DEHP has been shown to produce a wide range of toxic effects, particularly in male neonates where the infant’s reproductive system can be compromised.
- Other adverse effects on the lungs, heart and kidneys have been reported.15-16
- DEHP leaches out of the PVC into solutions stored in a fluid container and could affect patients, resulting in serious health consequences.
Products that exacerbate leaching:
- Chlordiazepoxide HCl
- Lipid Emulsions
- A significant number of drugs are not compatible with PVC and adhere to it.
- During the production and disposal process of PVC, dioxins and furans, which are environmentally detrimental, are produced.18 This group of structurally related chemicals persist in the environment and may bioaccumulate in animal food sources and human tissues.19
2 Umweltbundesamt, Berlin, Hrsg. (2/2007) Phthalate – die nützlichen Weichmacher mit den unerwünschten Eigenschaften: 3, 10.
3 Kroschwitz JI (1998) Kirk-Othmer Encyclopedia of Chemical Technology. Fourth Edition. John Wiley and Sons, New York.
4 IARC 2000 Monograph 77 on the evaluation of carcinogenicity to humans
5 National toxicology program, the US department of health and human services (11/2006) Center for the evaluation of risks to human reproduction: NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di(2-Ethylhexyl) Phthalate (DEHP). NIH Publication No. 06 – 4476.
6 Haishima Y, Seshimo F, Higuchi T, Yamazaki H, Hasegawa C, et al. (2005) Development of a simple method for predicting the levels of di(2-ethylhexyl) phthalate migrated from PVC medical devices into pharmaceutical solutions. Int J Pharm 2005; 298:126-42.
7 Hanawa T, Muramatsu E, Asakawa K, Suzuki M, Tanaka M, et al. (2000) Investigation of the release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing for intravenous administration.
Int J Pharm; 210:109-15.
8 Hanawa T, Endoh N, Kazuno F, Suzuki M, Kobayashi D, et al. (2003) Investigation of the release behavior of diethylhexyl phthalate from polyvinyl chloride tubing for intravenous administration based on HCO60.
Int J Pharm; 267:141-9.
9 Loff S, Kabs F, Witt K, Sartoris J, Mandl B, Niessen KH, Waag KL (2000) Polyvinylchloride infusion lines expose infants to large amounts of toxic plasticizers. J Pediatr Surg; 35:1775-81.
10 Loff S, Kabs F, Subotic U, Schaible T, Reinecke F, Langbein M (2002) Kinetics of diethylhexylphthalate extraction from polyvinylchloride-infusion lines.JPEN J Parenter Enteral Nutr; 26:305-9.
11 Loff S, Subotic U, Reinicke F, Wischmann H, Brade J (2004) Extraction of Di-ethylhexyl-phthalate from Perfusion Lines of Various Material, Length and Brand by Lipid Emulsions. J Pediatr Gastroenteral Nutr; 39:341-345.
12 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(4), 330-335.
13 Bourdeaux D, Sautou-Miranda V, Bagel-Boithias S, Boyer A, Chopineau J (2004) Analysis by liquid chromatography and infrared spectrometry of di(2-ethylhexyl)phthalate released by multilayer infusion tubing.
J Pharm Biomed Anal; 35:57-64.
14 Demore B, Vigneron J, Perrin A, Hoffman MA, Hoffman M (2002) Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous etoposide solution.J Clin Pharm Ther; 27:139-42.
15 Latini G (2000) Potential hazards of exposure to di-(2-ethylhexyl)-phthalate in babies. A review. Biol Neonate 78;269-276.
16 Tickner JA, Schletter T, Guidotti T, McCally M, Rossi M (1/2001) Health risks posed by use of Di-2-ethylhexyl phthalate (DEHP) in PVC medical devices: a critical review. Am J Med;39(1):100-11.
17 Bristol-Myers Squibb Company, Oncology Division. Taxol (Paclitaxel) Injection Administration, Equipment, 11/99 Equipment
18 European Union Risk Assessment Report. bis(2-ethylhexyl)phthalate (DEHP)
19 Hedley AJ, Wong TW, Hui LL, Malisch R, Nelson EA (2/2006) Breast milk dioxins in Hong Kong and Pearl River Delta. Environ Health Perspect; 114(2):202-8.