Male, Interrupted

Fay Flam, The Philadelphia Inquirer, October 27, 2008

At Children's Hospital of Philadelphia, surgeon Howard Snyder says he
and his colleagues repair the genitalia of roughly 300 baby boys every
year – about double what they did when he started his practice 30 years
ago.

He's not the only doctor who's noticed an increase in this kind of birth defect.

The most common of them, hypospadias, nearly doubled in the United
States between the late 1960s and early 1990s, according to researchers
from the Centers for Disease Control and Prevention.

Snyder suspects that while in the womb, some of these boys may have
been affected by hormone-disrupting chemicals called phthalates, found
in dozens of consumer products.

These chemicals give plastics flexibility, prevent perfumes from losing their scents, and keep nail polishes from chipping.

But in lab rats and mice, doses comparable to those we humans absorb
from the environment can disrupt the formation of male genitals and
otherwise feminize male animals. One small study from the University of
Rochester also linked these chemicals to irregularities in male genital
development.

Despite that, phthalates are added to numerous products ranging from deodorants to shower curtains to IV tubing in hospitals.

While the European Union has banned one type of phthalate in nail
polishes and several others in children's toys, the U.S. Environmental
Protection Agency is "assessing the toxicity of several phthalates,"
and awaiting results of a National Research Council study, expected
next year, a spokesman said.

The specific problem that concerns Children's Hospital's Snyder –
hypospadias – is considered an incomplete development of the male
organs, causing a boy's urethra to exit the underside of his penis. In
most cases, surgeons can reroute the urethra, but it can take several
difficult operations.

While there's yet no direct link between this defect and phthalates,
the dramatic increase in cases and the animal data have many doctors
concerned.

The American Chemistry Council, a trade group, defends the compounds, saying that the animal data may not apply to humans.

Chris Bryant, a council spokesman, cited a council news conference,
stating that dozens of studies found no link between phthalates and
adult diseases.

Industry and federal toxicologists also questioned the validity of
the one human study, he said, because it was small and flawed in its
methods.

But the animal data alone should prompt concern, said Theodore
Schettler, a physician and science director of the Science and
Environmental Health Network, an environmental advocacy group.

"There's a huge animal database showing how exposures to phthalates
during development can have effects at levels hundreds of times lower
than these needed to show any impact on an adult," he said.

Timing of the exposure matters, and the most harm may occur between
the eighth and 15th weeks of pregnancy, when a fetus' sexual
differentiation starts, he said.

"If my testosterone dropped by 20 or 30 percent for a couple of
days, it wouldn't matter," he said. "But for a developing fetus, it
could matter a whole lot if there was a substantial drop in
testosterone."

Phthalates fall into a group of chemicals called endocrine
disruptors because they either mimic or block the action of human
hormones. Phthalates interfere with the synthesis of testosterone.

Bisphenol A, another controversial chemical that is found in
plastics, can mimic female hormones. Consumers' concerns about
bisphenol A, which has been used for years to make plastics stiff, have
prompted some producers and retailers to announce in recent months that
they would stop using and selling it.

The attorneys general of New Jersey, Delaware and Connecticut sent
letters to 11 manufacturers two weeks ago, urging that the chemical be
eliminated from baby bottles and other children's products. A U.S. Food
and Drug Administration advisory committee is scheduled to discuss
conflicting reports about bisphenol A on Friday.

Phthlates affect males more than females, at least in animals,
because of the way sex organs grow. Developmental biologists say that
up until eight weeks, fetuses have the rudiments of both male and
female sex organs. After that point, those with a Y chromosome develop
gonads that are supposed to secrete testosterone, after which the male
hormone starts turning the fetus into a male.

Testosterone starts the construction of male genitalia. As part of
that, the opening of the urethra migrates from a position near the
testicles to the end of the penis. Hypospadias is thought to result
from incomplete masculinization.

No studies so far have directly connected hypospadias to phthalate
exposure, but one study by University of Rochester researcher Shanna
Swan suggested a link to anatomical variations.

Swan, a professor of environmental medicine and
obstetrics/gynecology, collected urine samples from several hundred
pregnant women and tested them for nine compounds known to come from
metabolizing phthalates.

Then she asked pediatricians to conduct a standard genital exam on 134 boys born to these women.

She found that boys whose mothers were most exposed to certain
phthalates were more likely to have undescended testicles and to have
smaller penises.

More pronounced was a feature known to indicate feminization in lab
animals – a shortened distance between the genitals and the anus. This
so-called anogenital distance, or AGN, is normally twice as long in
boys as in girls, as it is in male rats compared with females. Swan
found that boys of mothers with the highest phthalate levels during
pregnancy were much more likely to have relatively short AGNs.

Not all phthalates affected boys in the study. A common one that did
was called DBP, or dibutyl phthalate, an ingredient in nail polish,
hair sprays, perfumes, and other personal-care products.

The chemistry council said the study was too small to be considered valid.

University of California San Francisco urologist Larry Baskin said
he was trying to get grant money for a larger study to check these
findings. In the meantime, he said, "I think there's enough animal
evidence that it's reasonable to have a warning label for pregnant
women."

The problem is that no one is quite sure how people are getting
exposed, said the Environmental Health Network's Schettler. The human
body can clear out phthalates in a day or two, but many people seem to
continue picking it up from the environment.

Another common phthalate, DEHP, is used to make plastic flexible in
shower curtains, vinyl flooring, and IV bags and tubes. Some pregnant
women and their babies may get a harmful dose of DEHP in the hospital,
he said.

Pregnant women may also be absorbing DBP from personal-care products
and cosmetics, Schettler said. "You'll almost never find it on the
label," he said. Because it's often used as a solvent for fragrances,
companies are allowed to simply list "fragrance" on the label of
DBP-containing products.

He said that a few years ago he participated in a study along with
the group Health Care Without Harm. They bought dozens of common
personal-care products from supermarkets and pharmacies and analyzed
them for phthalates. "We found them in one form or another in 70
percent of the products we tested," he said.

Unfortunately, he said, regulatory agencies are swamped with
untested substances. "You're being exposed to a series of chemicals
that have not undergone safety testing because our regulatory system is
nonfunctional."

Snyder, at Children's Hospital, said he became concerned about
phthalates 15 years ago when he noticed the number of hypospadias cases
seemed to be rising.

And while hypospadias can be corrected, he said, it still can be traumatic for patients.

"It's a very tricky surgery," Snyder said. Though his specialty is
officially urology, he said, "you have to be well-versed in plastic
surgery to be able to handle these delicate tissues in boys between 6
and 9 months old." Some children need to come back for several
surgeries.

"It bothers kids to have genitalia that don't look standard," he
said. "Boys should be able to stand up and write their names in the
snow."

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