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 provocative.
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
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 Councilís Phthalate Ester Panel. The NTP panel was
Unconvinced by the study authorsí 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 studyís 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 FDAís
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 Childrenís 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 alternatives.
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 hospitalís NICU to safer non-DEHP
Medical devices within six months of FDAís 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. Iíve been very successful in
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 nationís largest medical device
manufacturer, Baxter International, which has yet to fulfill its 1999
promise to shareholders to develop a fully-expanded PVC-free product
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, FDAís failure to require labeling of products containing
DEHP and to move manufacturers toward safer product formulations is
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 FDAís
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
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 contents.
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
Source: Risk Policy Report via InsideEPA.com
Date: February 28, 2006
Issue: Vol. 13, No. 9
© Inside Washington Publishers
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