Environmental Science and Technology June 11, 2008

http://pubs.acs.org/subscribe/journals/esthag-w/2008/jun/science/jp_plasticizers.html

Tracking plastic's breakdown products

Researchers examine the metabolites of a popular plasticizer in sewage sludge.

By JANET PELLEY

A rapidly growing body of research has raised concerns about the

safety of phthalate plasticizers found in polyvinyl chloride (PVC)

products, cosmetics, and medical devices. Now, scientists are gaining

new insights by looking not just at the parent compounds but at their

metabolites as well.

The most widely used plasticizer is DEHP, or

di(2-ethylhexyl)phthalate, and millions of tons are produced

annually, says Jim Nicell, an environmental engineer at McGill

University (Canada). When added to PVC, DEHP lubricates the brittle

polymer, providing it with the well-known flexibility that makes it

ideal for use in building materials, household furnishings, and

medical devices such as intravenous tubes and bags.

Because it is not chemically bound to the plastic polymer, fat-loving

DEHP readily migrates out of products and is now ubiquitous in the

environment, Nicell says. It has been found in human breast milk,

blood, and urine as well as house dust, snow, and sewage sludge. The

European Commission has classified DEHP as a priority organic

pollutant and in 2006 proposed a water quality standard for DEHP of

1.3 micrograms per liter, Nicell adds. Denmark limits the

concentration of DEHP in sludge used in agriculture to 50 milligrams

per kilogram (mg/kg) dry weight.

"Environmental fate studies tend to focus on the parent compound, but

the unanswered question is, what does it turn into?" Nicell asks.

Expecting that DEHP would eventually degrade into CO2 and water,

Nicell and his colleagues at McGill were surprised to find that soil

microorganisms break down DEHP into metabolites that exhibit acute

toxicity in standard tests.

Nicell's new study tracked for the first time the DEHP breakdown

products in sewage sludge and found concentrations ranging from 1 to

228 mg/kg. "We don't have a handle on what is the long-term impact

associated with exposure to minute concentrations, [when combined

with] a whole bunch of other toxins or endocrine disrupters, on the

health and reproductive health of organisms," Nicell says.

However, a burgeoning body of work on human exposure to DEHP has

sprung up during the past 8 years, notes Russ Hauser, an

epidemiologist at Harvard University. Humans oxidize DEHP into a

different suite of metabolites compared with those from soil

microorganisms, starting with MEHP (mono-ethylhexyl phthalate) and

followed by four additional oxidative metabolites.

In an earlier study published in November 2006, Hauser and his

colleagues measured the concentration of DEHP metabolites in urine

samples collected from men at an infertility clinic and found a

positive association of MEHP with DNA damage in sperm. "When we

adjusted our statistical models for the oxidative metabolites, we

found a strong and consistent signal for MEHP that would otherwise

have been missed," Hauser says.

Scientists have been able to establish DEHP and its breakdown

products as antiandrogenic in rodents, according to Shanna Swan, an

epidemiologist at the University of Rochester. Exposure to DEHP in

utero puts a damper on testosterone production in fetal male rats,

which leads to undescended testicles, penile deformations, and a

shorter anogenital distance.

The National Toxicology Program's Center for the Evaluation of Risks

to Human Reproduction concluded (PDF Size: 4.46 MB) in November 2006

that DEHP in medical devices raises serious and significant concerns

that normal development of the male reproductive tract in humans

could be undermined.

In 2005, Swan and her colleagues looked for and found shortening of

anogenital distance in human male infants, similar to that found in

exposed rats; the effect was associated with higher exposures to four

phthalates but not to DEHP. Swan is repeating the study with a larger

sample size and more DEHP metabolites than in the earlier study.

Because of the known reproductive and toxic effects in animals,

California has stepped in to regulate DEHP, explains Sam Delson,

deputy director for external and legislative affairs at the

California EPA. Beginning on January 1, 2009, California regulators

will prohibit manufacturers from using DEHP in any toy or child-care

article and will prohibit three other phthalates from being used in

any toy or child-care article intended for use by children under 3

years of age, if the item can be placed in a child's mouth. The

regulation is nearly identical to one finalized in the EU in 2006.

The U.S. Congress is close to approving a bill (H.R. 4040) that would

establish a federal ban on phthalates in children's toys.

The U.S. Food and Drug Administration (FDA) in 2002 recommended that

hospitals use alternatives to DEHP-containing plastics for vulnerable

populations such as premature baby boys, mothers pregnant with male

fetuses, and boys nearing puberty, says Ted Schettler, science

director for the Science and Environmental Health Network, an

advocacy organization. To date, FDA has resisted calls from a

coalition that includes the American Medical Association (the top

advocacy group for doctors) and leading hospitals to require

manufacturers to label medical devices that contain DEHP.

Given how much is known about the risks of DEHP from animal data and

that we have some understanding of the molecular mechanisms, serious

thought must be given to how to reduce human exposure, Hauser says.

"Health Care Without Harm [an advocacy group] has a position stating

that people shouldn't be exposed to DEHP and that we should be moving

away from PVC medical devices to those made out of alternative

materials," Schettler adds.