by Peter M. Galland, Industry Manager for Regulated Compounds, Teknor Apex Company
While phthalate esters such as DEHP are the most widely used plasticizers for flexible PVC medical compounds and have been for fifty years, issues concerning their possible effects on human health have caused some device manufacturers to consider compounds containing alternative plasticizers. Sometimes the pressure to do so is considerable. As a result, it is possible to make a decision based on one factor in favor of a particular alternative plasticizer rather than on a comparative study that takes all of the important considerations into account.
There are a number of alternative plasticizers on the market. While Teknor Apex is best known as a manufacturer of medical-grade PVC compounds, we also produce some of these plasticizers. Two alternatives that have received considerable attention in the medical device industry are TOTM, a trimellitate ester which Teknor Apex manufactures and sells primarily in the wire and cable industry because of its low volatility, and DOTP, a terephthalate which we do not produce. Teknor Apex can and does use both plasticizer types in producing medical-grade flexible PVC compounds. As part of a program to support customers in weighing the pros and cons of available alternative plasticizers, we have determined that DOTP provides a better balance of properties than TOTM for many medical device applications.
TOTM is a monomeric plasticizer whose high molecular weight makes it less mobile than other alternative plasticizers and, for that matter, than DEHP as well. In spite of its chemical designation as a terephthalate, DOTP is classified as a non-ortho-phthalate, different from DEHP in terms of animal toxicology and metabolization.
The high molecular weight of TOTM is the source of an advantage over DOTP having to do with the phenomenon of stress cracking in connectors or other rigid components that interface with flexible PVC components such as tubing. The stress cracking is caused by the migration of plasticizer to the interface with the rigid component, and it is most pronounced in the case of amorphous rigid materials like polycarbonate. The stress cracking or crazing that weakens the rigid component takes place more slowly with TOTM than with DOTP.
It is important to put this advantage of TOTM in perspective. DOTP may cause more crazing than TOTM but resists crazing better than other alternative plasticizers and even better than DEHP. TOTM is also outperformed in this regard by polymeric plasticizers. Over the years, moreover, device manufacturers have avoided serious crazing issues with DEHP through appropriate design and other measures. In addition, it is now possible to minimize the issue of stress cracking by using specially formulated, stress crack resistant rigid PVC compounds in place of polycarbonate for connectors.
The crazing phenomenon is only one of the factors that must be taken into consideration when deciding between TOTM and DOTP, or indeed between any plasticizers. Key factors include:
- Cost. DOTP-plasticized PVC compound of 75 Shore A durometer currently costs 10 to 15 cents per pound less than one plasticized with TOTM. This is chiefly because TOTM is far more expensive. In addition, TOTM is a much less efficient plasticizer than DOTP, meaning you have to use more TOTM to achieve the same durometer—and plasticizer today is more expensive than PVC resin.
- Purity. If processed in truly dedicated equipment, DOTP can be produced nearly free of DEHP contamination. DOTP plasticizer producers specify a DEHP content of less than 50 parts per million, but almost all shipments contain significantly less than that. In contrast, TOTM can contain as much as 2,000 ppm of DEHP and is never free of it. This is because the process for making trimellitic anhydride simultaneously produces some phthalic anhydride which, when esterified with the di-2ethylhexyl alcohol used to make TOTM, is completely converted to inseparable DEHP.
- Toxicology. All of the toxicology data available for PVC plasticizers is based on rodent toxicology. In a comprehensive European1 study, DEHP is reported to have a NOAEL (no observable adverse effect level) of 4.8 milligrams per kilogram of body weight, while TOTM has a NOAEL of 100 milligrams (see table). By comparison, DOTP is listed at 500-700 milligrams, making it 100 to 140 times safer than DEHP for rodents and 5 to 7 times safer than TOTM. The same study listed NOAELs for ATBC (acetyl tributyl citrate), DINCH (di-isononyl cyclohexanoate), and DOA (di-octyl adipate) plasticizers at 100, 107, and 200, respectively. TOTM was also cited to be reproductively toxic for the rodents tested, whereas DOTP, ATBC, and DINCH had no reproductive effects.
- Performance. Because of its higher molecular weight, TOTM is absorbed into the porous PVC resin particles during compounding much more slowly than is DOTP or any of the other monomeric plasticizers. A result of poor or slow absorption is un-plasticized or insufficiently plasticized PVC resin particles, which ultimately are manifested in clear flexible tubing or film as gels.
- REACH status. Four years ago, TOTM was placed on a list for future consideration as one of the SVHCs (substances of very high concern) under the European REACH legislation.2 Although it is unlikely that anything will come of that listing, the mere fact that it was considered reflects on how similarly some analysts think the toxicology of TOTM mimics that of DEHP, with its only saving grace being its lower solubility and mobility due to its higher molecular weight.
In all respects, except for the issue of crazing, DOTP appears to be the preferable candidate for replacing DEHP. In fact, although DOTP is a relative newcomer to the global marketplace, it already outsells TOTM by a ratio of 12 to 2. Of all of the plasticizers that have emerged as alternatives to DEHP, DOTP has the largest market share.3
- EU Health and Consumer Protection Directorate-General, Scientific Committee on Emerging and Newly-Identified Health Risks (SCENIHR) p. 17.
- REACH substance evaluation at European Chemicals Agency website (echa.Europa.eu) for chemical listing CAS No. 3319-31-1 (TOTM).
- Paul Daniels, SpecialChem, Alternatives to Phthalate Plasticizers, Slide 13, 2014.