Ted Schettler and Mark Rossi
An environmentally sustainable and safe plastics industry is a laudable goal. Unfortunately, those who critique any aspect of the plastics' supply chain are too often characterized as being opposed to the use of all plastics, typically with no evidence to support that claim. But let's be clear:
Specific concerns about the patient safety of PVC medical devices plasticized with di (2-ethylhexyl) phthalate, or DEHP, are based on a large body of scholarly scientific evidence.
During the past two years, the National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction (NTP CERHR) and the Food and Drug Administration independently reviewed that literature. Each focused on the developing male reproductive tract as the system most sensitive to DEHP exposure. Each noted the lack of any human data addressing that biological end point. Each carefully addressed the relevance of animal data to humans, mechanisms of toxicity, the importance of route of exposure, pharmacokinetics, metabolism, and age-related susceptibility.
NTP CERHR concluded: "The available reproductive and developmental toxicity data and the limited but suggestive human exposure data indicate that exposures of intensively treated infants/children can approach toxic doses in rodents, which causes the panel serious concern that exposure may adversely affect male reproductive tract development." FDA went further, developing "tolerable intake" values for DEHP via oral and parenteral routes of exposure. They identified specific medical therapies that may result in levels of exposure to the plasticizer that exceed those amounts. FDA also noted that patients commonly receive multiple therapies during a hospitalization, resulting in additive DEHP exposures. FDA concluded that "children undergoing certain medical procedures may represent a population at increased risk for the effects of DEHP."
Further, DEHP is a ubiquitous environmental contaminant. General population dietary exposures range from 25-75 percent of FDA's oral tolerable intake, independent of any medical therapy of any kind. Given that background exposure, the NTP CERHR concluded that "ambient oral DEHP exposures to pregnant or lactating women may adversely affect the development of their offspring." Any additional exposure from DEHP-containing medical devices would only add to that concern.
The FDA report also noted that nonsystemic adverse effects of DEHP in patients can be clinically significant. For example, the safety assessment points out that DEHP can alter the hemocompatibility of PVC tubing, causing platelet aggregation and complement activation, resulting in clinically important microemboli. Brain infarcts and dysfunction have been attributed to DEHP leaching from PVC tubing, as well as infarcts of lungs and kidneys. DEHP can also result in adsorption of drugs to PVC tubing.
Supporters of DEHP-containing PVC medical products argue that it is a "proven safe material." ("Scientific eyes open to valid PVC concerns," Page 6, Nov. 5 Mailbag).
Based on what evidence? As noted by the NTP panel, human data for most end points are exceedingly sparse. No one, for example, has ever studied the impacts of DEHP exposure on the developing human male reproductive system. Instead, relevant animal studies, the standard method for examining the health effects of potential chemical hazards in humans, led to the NTP and FDA conclusions. An epidemiological study of the impacts of DEHP exposure on the developing human male reproductive tract has never been done, and it is unlikely that it ever will be done. Why? Largely because of the complexities
associated with an extremely long latency period between exposure and assessment of
reproductive function, not to mention numerous interceding effect modifiers. No data - no problem?
Hardly. Lack of human data does not equate with evidence of safety.
Given the availability of existing alternatives for many DEHP-containing medical products, as well as new products soon to enter the marketplace, the time has come to stop defending the widespread use of this reproductive and developmental hazard and move on to the next generation of materials.