Anaheim, Calif. — Eastman Chemical Co. conducted a clinical trial to evaluate a non-phthalate plasticizer for medical applications and the results indicate it could become a “lead alternative” to using DEHP to soften PVC blood bags.
DEHP, or di-2-ethyyllhexyl phthalate, has provided the medical industry with a stable ortho-plasticizer for many years and has even been found to extend the length of time blood can be stored to 42 days.
However, DEHP migrates at low levels into the blood product. And exposure to DEHP has been shown to have adverse effects on the development of reproductive systems in male laboratory animals.
The European Commission has classified DEHP and three other phthalates as substances of very high concern and banned their use in electrical equipment by July 2019. A similar restriction for medical devices about to hit the market is expected to be enforced in July 2021. In the meantime, some companies and scientists have been trying to come up with a viable Plan B for blood bags.
“If the Europeans do put a law in place saying by 2020 you won’t be able to use a whole host of materials, one of which is DEHP, that will drive change in the industry,” Mark Brucks, Eastman’s market development manager for plasticizers, said at the Medical Device & Manufacturing trade show, held Feb. 7-9 in Anaheim.
“The year 2020 seems far away,” he added, “but in the medical world that’s tomorrow.”
Eastman partnered with the BloodCenter of Wisconsin to test Eastman 168 SG, which is a sensitive-grade di-2-ethylhexyl terephthalate (DEHT). Although structurally and functionally similar to DEHP, DEHT is different from a metabolic and toxicological standpoint. It is not an ortho-phthalate, carcinogen, mutagen or reproductive toxicant.
In the clinical trial, overall, the DEHT bags showed comparable performance to the DEHP bags, which “suggests it should be considered a lead alternative plasticizer for PVC blood bags,” the study concluded.
Dr. Kathleen Puca, medical director of BloodCenter, oversaw the evaluation at the facility, which is part of Verti, a Milwaukee-based non-profit organization that specializes in blood services including diagnostic testing, donation and research.
“Our work with Eastman has provided valuable results that will benefit the blood banking industry,” Puca said in a news release. “The DEHT trial results offer new light about a well-established plasticizer that has now been proven to have an even broader application within health care: providing safer blood products.”
Based in Kingsport, Tenn., Eastman introduced the trademarked Eastman 168 non-phthalate plasticizer for PVC in 1975 and it has been widely used for gaskets, hosing, flooring, wire and cable in the automotive and consumer goods markets. Eastman 168 SG is an enhanced grade for more demanding applications, such as medical devices, food contact, toys and child care products.
The chemical company has a big franchise in terms of materials for the medical industry, but it can’t conduct tests with human blood because that requires a different kind of expertise.
“For this study we went to the marketplace and said, ‘If we see an ultimate end to the use of DEHP, what will help the market be more comfortable with alternatives,’” Brucks said. “So we partnered with BloodCenter of Wisconsin to do the work.”
The center’s clinical study of Eastman 168 SG looked at the stability of red blood cells in containers plasticized with the DEHT and DEHP materials. Made in the bone marrow, red blood cells contain a protein called hemoglobin that carries oxygen to body tissue. The cells also remove carbon dioxide by transporting it to the lungs to be exhaled. The cells typically live about 120 days.
For the trial, blood from three donors was mixed and separated into red blood cells and plasma. The red blood cells then were divided into a control group put in a DEHP PVC blood bag with a standard blood preservative called AS1; another group in a DEHT PVC blood bag with AS1; and the last group in a DEHT PVC blood bag with an alternative blood preservative solution called PAGGSM.
Different parameters of the red blood cells were measured three times over 42 days, including the percent of hemolysis, or rupturing of the cells.
How did the study groups do? Brucks said the Eastman material with PAGGSM performed comparably to the control group. The other group, which was the Eastman material with the standard blood preservative, showed less protection against hemolysis, he said, but still was within the regulatory limits set by the European Union and U.S. Food and Drug Administration.
In both cases, Eastman’s performance wasn’t quite as good as DEHP, but in terms of plasticizer migration their results were better.
“We actually showed 72 percent less plasticizer going into the red blood cell solution than DEHP, which I think is viewed positively. That’s a fairly big deal,” Brucks said.
The findings look promising for the Eastman brand. Now what?
“All we can do as a third-party company is give people guidance that based on normal testing and protocols, our formulation didn’t show any particular issues,” Brucks said. “Our data is a tool that gives our customer confidence that in their formulation they will see similar performance.”
Eastman also is following up on this work. More testing also will be done on plasma and the results will be out later this year.
Although a blood bag seems a simple item, it isn’t, Brucks said, noting that it holds living cells that go into a living person.
“As you have more and more intimate contact with a patient, typically a higher level of validation and testing needs to be done,” he said. “It takes a lot of time and effort to validate that any material changes are acceptable.”
Eastman and the BloodCenter of Wisconsin have put in some of that time and effort.
“What we’re trying to do is present information so if someone does have a concern around DEHP, they have enough data to say we have an alternative that we can more easily vet,” Brucks said.