Scientists to EPA: Risks of Chemicals That Alter Male Hormones Should Be Analyzed Together

A national panel of experts says EPA must change its focus and analyze chemicals that endanger male reproduction
cumulatively or it will “seriously underestimate” the risks to human health

Concluding that nearly everybody is exposed to a mix of chemicals that could be damaging male reproductive health, a national panel of scientists on Thursday advised the U.S.
Environmental Protection Agency to shift its focus and group them together when judging how much of a danger they pose.

The committee, assembled by the National Academy of Sciences, looked specifically at phthalates, controversial compounds widely found in consumer products. Phthalates soften plastic to
make vinyl for toys, building materials, medical devices and other items, and they also are used in fragrances and other beauty products.

The recommendation to combine the compounds when analyzing their threats to human health would mark a critical change in EPA strategy. It would likely lower the total amount of
phthalates the agency considers safe for people and ultimately could lead to strict regulations on their use.

By analyzing each chemical individually, the EPA underestimates the health risks of phthalates, the committee reported. In human bodies, phthalates combine, amplifying the effects on
male reproduction.

By only doing one, we underestimate the risk,” said Deborah Cory-Slechta, a professor of environmental medicine at University of Rochester School of Medicine and Dentistry who chaired
the National Research Council’s phthalates committee.

The recommendations could have far-reaching implications beyond phthalates, transforming how the EPA determines to what degree people will be exposed to a variety of chemicals and
pollutants.

The committee said other compounds, such as bisphenol A and pesticides, also linked to effects on male hormones should be grouped with phthalates in the EPA’s risk analysis.

“A focus solely on phthalates to the exclusion of other antiandrogens would be artificial and could seriously underestimate cumulative risk,” the report says.

EPA scientists asked the National Academy of Sciences for advice on how to assess phthalates because they know many have the same effects.

Peter Preuss, director of the EPA’s National Center for Environmental Assessment, said his “best guess” is that the agency will conduct the recommended cumulative assessment for
phthalates. But he said his staff just received the 160-page report and it must first analyze the technical details of how the committee says to proceed.

“The Academy said very clearly that they think there is sufficient information to do this, so that is our next step,” Preuss said.

“There are many chemicals that act by many different mechanisms but the final result is a series of impacts on the developing male reproductive system,” he said. “The Academy said these
things are important—focus on the endpoint, the [health] effect, and work from that. They are trying to simplify this process.”

Going even further, the scientists urged the EPA to consider broadening all its assessments to include cumulative effects of compounds with the same health effects.

That, for example, might lead to combined analysis of compounds that affect the brain, female reproduction, lung cancer, or heart disease.

The report bolsters a relatively new scientific argument that cumulative exposure to chemicals and pollutants should be considered when setting safe doses for each.

Many environmental groups and public health experts have urged EPA to conduct risk assessments that combine chemicals, so they welcomed the committee’s findings.

Shanna Swan, director of the University of Rochester’s Center for Reproductive Epidemiology and one of the leading scientific experts on phthalates, called the cumulative approach “the
crucial next step” in addressing environmental chemicals that disrupt hormones.

“It is extremely important to conduct cumulative risk assessments to protect public health,” said Dr. Sheela Sathyanarayana, acting assistant professor of pediatrics at University of Washington. “Unlike in scientific experiments, humans are exposed to multiple chemicals everyday,” she
said, so combining the chemicals “can help identify how these multiple exposures could be leading to health outcomes in the general population.”

Swan and Sathyanarayana were not on the panel, but both have studied phthalates. Sathyanarayana’s research linked babies’ phthalates to baby lotions, powders and shampoos. Swan
and her colleagues reported in 2005 that the chemicals were associated with signs of feminized genitalia in newborn boys.

Tests conducted by the U.S. Centers for Disease Control and Prevention show that nearly all people, even newborns, carry traces of numerous phthalates in their bodies. Fetuses, infants
and children are considered most at risk.

Europe and the United States have restricted phthalates in toys and other children’s products, and the EU has banned some in cosmetics. But a variety of phthalates are still in a host
of consumer products.

A child may ingest phthalates through chewing on a rubber duck, an infant may be exposed from intravenous tubes in neonatal wards, and a fetus may absorb them through his mother’s use
of perfumes, lotions, nail polishes and other cosmetics.     

Industry groups have argued that there is insufficient evidence to group phthalates together. But the panel of 13 scientists disagreed.

“Our committee concludes that there are common adverse effects” for many phthalates and “we believe that EPA should go ahead and conduct a cumulative risk assessment,” Cory-Slechta
said. She said the scientists found sufficient data, primarily from laboratory animal tests, to justify the new approach for phthalates immediately.

“There is a growing body of literature, particularly in rats, showing effects of phthalates on development of the male reproductive system,” she said.

Several types of phthalates mimic or block testosterone and other androgens, which are the sex hormones that guide formation of testicles, sperm and other parts of the male reproductive
system. In animal tests, exposure leads to infertility, malformed penises and abnormal testicles, which scientists call the “phthalate syndrome.”

In the past, EPA has done cumulative risk assessments when substances were structurally similar in their chemical makeup or acted in the same way. But the committee says the EPA should
instead group compounds according to “what they ultimately do”—the effects on human health, Cory-Slechta said.

The American Chemistry Council, representing industries that produce phthalates, said Thursday that it has “some reservations about how to conduct the cumulative risk assessment on
substances” that do not act in the same way.

“This is remarkably ambitious and could be problematic for EPA considering that this essentially could result in a study without limits, financially or otherwise,” said Chris Bryant,
managing director of the group’s Chemical Products & Technology Division.

“Congress has asked the Consumer Product Safety Commission to conduct a cumulative risk assessment on phthalates and there is a question as to whether a simultaneous EPA study would be
redundant,” he assed.

The chemical industry also wonders how this would be reconciled with another National Academy report earlier this month that advised EPA to more strongly focus its risk assessments for
chemicals.

Cory-Slechta agreed that a cumulative assessment would mean a “real paradigm change for EPA” and “might prove somewhat challenging for them.” One obstacle for EPA scientists is that not
all phthalates have the exact same effects or the same potency.

“EPA certainly has been moving in the direction of cumulative risk assessment, largely for chemicals structurally similar and ones that act in a similar way. This is the next step–
focusing on adverse outcomes,” she said.

“This committee believed very strongly that the conceptual approach should be broadly applicable” to other chemicals, too, she added.

For instance, EPA could evaluate the risk of combined exposures to lead, mercury, and polychlorinated biphenyls—all of which can damage developing brains and reduce children’s
IQs, the committee said.

“The question is do we have enough data on the individual chemicals to put into an assessment like this.  For something like phthalates, the answer is definitively yes,”
Sathyanarayana said.

But, she added, “for other chemicals that have not been researched as extensively, it may be difficult to find specific information for let’s say, fetal effects, and this point is
highlighted in the [committee’s] summary.”

One example where EPA does not have enough data to combine all the compounds is nanoparticles, which used in sunscreens and a variety of consumer products, she said.

The EPA’s Preuss acknowledged that “there clearly will be challenges to applying this to chemicals beyond the phthalates,” even when looking at just male reproduction. His staff will
have to resolve questions about how much scientific evidence is needed before including a chemical.

“We sort of have a role in the agency of doing the difficult assessments,” he said. “Fitting something in like this with the current staffing we have is one of the challenges, clearly.”

Sathyanarayana agreed with the committee’s recommendation to group chemicals together according to what they do to the body, not just how they do it. “I think it is very important,” she
said. “This shift in focus could lead to a much better assessment of how mixtures affect the development of adverse health outcomes.”

Beyond male reproductive health, the committee’s report raises interesting questions about how Preuss’ staff should determine a safe amount of many chemicals, including a long list of
air pollutants that can cause the same respiratory and cardiovascular damage.

“I’m sure there will be a huge amount of discussion following up on this report about how broadly we can apply the principles they recommend,” Preuss said. “I think it will be quite
interesting and controversial.”

This article originally ran at Environmental Health News, a news source published by Environmental Health Sciences, a nonprofit media company.

Marla Cone