Risk Policy Report via InsideEPA.com (Vol. 13, No. 9)  [Printer-friendly version]
February 28, 2006


By Ted Schettler, M.D., MPH

As evidence of the hazards of di-2-ethylhexyl phthalate (DEHP)
Continues to mount, the inevitable question arises, "When do we know
enough to act to protect people from unnecessary and potentially
harmful exposures?" Concerns about the safety of DEHP, a PVC
plasticizer, have intensified since it became apparent that developing
organisms are far more susceptible to DEHP exposures than adults.
Hundreds of animal studies confirm the particular vulnerability of the
developing male Reproductive system and have begun to define
mechanisms of toxicity, including impaired testosterone synthesis.
Birth defects, pathologic testicular changes, decreased sperm
production, and altered hormone levels are caused by developmental
exposures to DEHP. Lowest adverse effect levels in developing
organisms are orders of magnitude lower than doses necessary to cause
reproductive system impacts in adults.

Human studies report ubiquitous DEHP exposures in the general
population, with some concluding that the reference dose is exceeded
among those who are most highly exposed. Studies of infants in
neonatal intensive care units show even higher exposure levels from
DEHP- containing medical devices. Based on animal tests, these
exposures Occur during developmental windows of heightened
sensitivity. Measurements of newly identified metabolites of DEHP have
enriched our understanding of mammalian toxicokinetics and suggest
that previous estimates of DEHP exposure are too low. The first
studies of DEHP exposure effects in infants are inconclusive but

Two expert panels of the National Toxicology Program (NTP), the US
Food & Drug Administration (FDA), a Health Canada expert panel, and
the European Union have all concluded that the animal studies of DEHP
are likely to predict human health impacts and raise serious concerns.
These government-sponsored panels say health care delivery with DEHP-
containing PVC medical products can be a clinically significant source
of DEHP exposure, and infants receiving intensive medical care are
most at risk.

In 2002, FDA issued a Public Health Notification warning health care
providers to use available DEHP-free medical devices while treating
certain vulnerable patient populations, including critically ill
infants. http://www.fda.gov/cdrh/safety/dehp.html. In October 2005, a
second NTP expert panel reviewed the last several years of research
findings and again expressed "serious concern" regarding infants
receiving intensive medical treatments with DEHP-containing devices.

Recent studies of infants receiving intensive medical therapy with PVC
medical devices reported levels of DEHP metabolites in their urine
similar to those associated with adverse impacts in laboratory
animals. One of the studies also contained some good news. Comparing
infants in two Harvard-affiliated Boston Neonatal Intensive Care
Units, the study found significantly lower DEHP levels in the babies
receiving care at the hospital that had switched to DEHP-free medical
devices for some applications. Health care providers at that
institution had taken prudent action to protect their vulnerable
patients from unnecessary exposures to DEHP while continuing to
provide high-quality care.

Defenders of PVC/DEHP products cite studies in marmosets that
Reportedly show no harm from DEHP exposures. Marmosets are members of
a primate species with male hormonal regulatory systems that
significantly differ from humans. For instance, testosterone levels
are normally high in marmosets, and they are relatively insensitive to
changes in steroid hormone levels, unlike humans. This is not a
trivial detail when evaluating a chemical that interferes with
testosterone synthesis. It limits the utility of marmosets as a model
for studying DEHP toxicity In humans. Moreover, no study has ever
examined the impacts of fetal or neonatal exposure to DEHP in non-
human primates.

The recent NTP expert panel also reviewed a relatively new but
unpublished, industry-sponsored marmoset study submitted by the
American Chemistry Council's Phthalate Ester Panel. The NTP panel was
Unconvinced by the study authors' curious rationale for omitting from
the data analysis some animals that apparently showed significant
impacts from exposure. Subsequently, a reproductive biologist
commissioned by the Phthalate Ester Panel to review that study and
comment on the appropriateness of using marmosets as a relevant animal
model was also unable to explain why those data were omitted from the
analysis. He further commented on the study's poor design and
execution. (

PVC/DEHP defenders also look for safe harbor in the lack of proof that
DEHP harms humans. Human studies will require accurate DEHP exposure
assessment in male fetuses and infants, followed by long-term follow-
up as these children enter their reproductive years in order to find a
potential relationship between early life exposures and later
reproductive function. The prospects for such a study are slim, and
the results would not be available for decades.

DEHP-free alternatives are readily available for nearly all uses in
health care. Replacing DEHP with another plasticizer in a PVC device
of course raises questions of the safety of the alternative. To be
sure, other plasticizers must also undergo rigorous scrutiny and FDA
approval. Some alternative polymers, however, such as polypropylene
and polyethylene, among others, do not require plasticizer additives
of any kind, and concern about their leaching is not an issue. A list
of PVC- free medical devices, manufacturers, and alternative materials
is available at http://www.noharm.org/us/pvcDehp/reducingPVC.

Some major health care institutions are responding to the FDA's
notification by phasing out PVC medical devices and seeking safer
alternatives -- including Kaiser Permanente, the largest non-profit
health care provider in the United States; Catholic Healthcare West,
Miller Children's Hospital, Lucille Packard NICU at Stanford
University, and many others. The largest group purchasing
organizations in the health care industry have committed to support
labeling of PVC and DEHP medical products and offer DEHP-free

In the experience of clinical practitioners, DEHP-free alternatives
Have similar costs and are just as safe and effective. Valerie
Briscoe, a neonatal clinical nurse specialist at John Muir Medical
Center, a 550- bed hospital in Northern California with the busiest
birth center in Its county, was able to switch her hospital's NICU to
safer non-DEHP Medical devices within six months of FDA's public
health notification.

"We found alternatives that were as adequate in providing therapy with
no substantial cost impact to the hospital. This was a relatively easy
process for me," Briscoe said. "I would say that 99 percent of the
products have alternatives out there. I've been very successful in
finding alternatives."

Catholic Healthcare West (CHW), the largest Catholic health-care
system in the western United States, announced in November a five-
year, $70 million contract to B. Braun Medical Inc. for PVC-free/DEHP-
free intravenous bags, solutions and tubing.

"We have been actively advocating for PVC/DEHP-free supplies from our
vendors since 1997. B. Braun has stepped up to the challenge as the
first supplier with the capacity to deliver PVC- and DEHP-free
supplies to all 40 of our hospitals," said Lloyd H. Dean, CHW
president/chief executive officer, in a press release announcing the
contract. CHW previously contracted with the nation's largest medical
device manufacturer, Baxter International, which has yet to fulfill
its 1999 promise to shareholders to develop a fully-expanded PVC-free
product line.

Despite these promising developments, many hospitals across the
country are unaware of concerns about DEHP and continue to use PVC
medical devices, unnecessarily exposing vulnerable patients to high
levels of DEHP. Given the weight of the evidence and the availability
of safer alternatives, FDA's failure to require labeling of products
containing DEHP and to move manufacturers toward safer product
formulations is disturbing.

Because of widespread use of phthalates in a variety of consumer
products and general environmental contamination, exposures are
ubiquitous in the general population. Unfortunately, no regulatory
agency looks at total exposures from all sources when making
decisions. Phthalate-containing products are under the regulatory
authority of the Environmental Protection Agency, which regulates
industrial chemicals, the Consumer Product Safety Commission, and FDA.
Even within FDA, which is responsible for food contaminants,
pharmaceutical ingredients, medical devices, and cosmetics -- each of
which may contain phthalates -- there is virtually no attempt to look
at the bigger picture. The focus is generally on one source or one
product at a time. When FDA's medical device division considers the
safety of exposures to DEHP, it considers only medical devices and not
the real world of population-wide exposures from the several million
tons of phthalates released into the environment annually.

Even within this Balkanized regulatory system, however, justification
for replacing of DEHP-containing medical products is sufficient.
Despite that justification, FDA posted its "Public Health
Notification: PVC devices containing the plasticizer DEHP" on its
website with little publicity. The agency has yet to issue a guidance
that would require labeling of DEHP-containing medical products and
responsibly move the device-manufacturing sector toward a new
generation of safer materials. As a result, even those health care
providers who are aware of the concerns surrounding DEHP are often
unable to identify potentially problematic devices in their inventory.
Informed purchasing decisions require full disclosure of product

We know enough to act. There is no longer any justification for
hospitals to continue using PVC/DEHP devices where alternatives exist,
particularly in vulnerable patients. Medical device manufacturers
Should provide PVC-free/DEHP-free devices that hospitals increasingly
seek. And, FDA should use its authority to meet its public trust
responsibility: require labeling of DEHP-containing PVC medical
devices and move the medical device market to safer alternatives by
requiring substitution where suitable alternatives exist. Ted
Schettler is the Science Director of the Science and Environmental
Health Network

Source: Risk Policy Report via InsideEPA.com

Date: February 28, 2006

Issue: Vol. 13, No. 9

 Inside Washington Publishers