Scientific American  [Printer-friendly version]
May 1, 2006


Harmless Levels of Chemicals Prove Toxic Together

[Rachel's introduction: One chemical alone may do no harm in low
doses, but in conjunction with a few of its peers, even in doses that
individually seem safe, it may inflict serious harm.]

By David Biello

One chemical alone may do no harm in low doses, but in conjunction
with a few of its peers, even in doses that are individually safe, it
can inflict serious harm. New research in frogs shows that a mixture
of nine chemicals found in a seed-corn field in York County, Nebraska,
killed a third of exposed tadpoles and lengthened time to
metamorphosis by more than two weeks for the survivors.

Biologist Tyrone Hayes and his colleagues at the University of
California, Berkeley, have spent the past four years testing four
herbicides, two fungicides and three insecticides commonly used in
American cornfields. Individually, the chemicals had little effect on
developing tadpoles at low concentrations, such as about 0.1 part per
billion. But when Hayes exposed them to all nine at the same low level
in the laboratory--the lowest level actually found in the field--the
future frogs fell prey to endemic infection. Those that survived ended
up smaller than their counterparts raised in clean water--despite
taking longer to mature into adults. "In humans, this is like saying,
'The longer you are pregnant, the smaller your baby will be," which
means the womb is no longer a nurturing environment," Hayes notes.

Hayes's study joins a growing body of work showing that chemicals in
combination can produce a wide range of effects even at low
concentrations. Rick Relyea of the University of Pittsburgh has shown
in several studies that tadpoles exposed in their water to low levels
of a single pesticide and the smell of a predator will face
significantly higher mortality rates. For instance, about 90 percent
of bullfrog tadpoles died from exposure to the pesticide carbaryl when
the smell of predatory newts was present, whereas no tadpoles perished
if exposed to each individually. "The pesticide may be inducing a
general stress in the tadpole that, when combined with another
stressor, becomes deadly, Relyea argues.

It is not just pesticides that show a mixture effect. Phthalates--
chemical softeners that make polymers flexible--can interfere with the
sexual development of male rats. "We have males treated with
phthalates where the testes are under the kidneys or floating around
in the abdominal cavity," explains L. Earl Gray, Jr., a biologist at
the Environmental Protection Agency and codiscoverer of this
deformity, which has been dubbed phthalate syndrome. Gray has also
found that various kinds of phthalates in combination either with one
another Or with certain pesticides and industrial effluents exert ever
more powerful effects. For example, two phthalates at concentrations
that on their own would not produce much deformity combined to create
defective urethras (hypospadias) in 25 percent of exposed rats.

Besides adding to the issue of endocrine disruption--whether
industrial chemicals are mimicking natural hormones--the findings on
mixtures pose an incredible challenge for regulators. With tens of
thousands of chemicals in regular use worldwide, assessing which
combinations might prove harmful is a gargantuan task. "Most of the
offices in the agency recognize that we cannot operate via the idea of
'one chemical, one exposure' to an individual anymore. We need to look
at broader classes of compounds and how they interact," says Elaine
Francis, national program director for the EPA's pesticides and toxics
research program. But such testing has a long way to go to reach any
kind of regulation, particularly given industry's qualms about the
validity of existing research.

Marian Stanley, who chairs the phthalates panel for the American
Chemistry Council, notes that at least one study showed that rodents
suffering from phthalate malformations could still mate and have

"The additivity of phthalates alone are on end points that may not
have any biological relevance," she says.

Nevertheless, evidence continues to accumulate that mixture effects
are a critical area of study. In its National Water Quality
Assessment, the U.S. Geological Survey found that a sampling of the
nation's streams contained two or more pesticides 90 percent of the
time. "The potential effects of contaminant mixtures on people,
aquatic life and fish-eating wildlife are still poorly understood,"
states hydrologist Robert Gilliom, lead author of the study. "Our
results indicate, however, that studies Of mixtures should be a high


Sidebar: Human Disruption

By David Biello

Besides affecting amphibians, endocrine disruption -- chemical
interference with hormonal cascades involved in development--may also
be happening in humans. Shanna Swan of the University of Rochester has
linked fetal exposure to phthalates and genital changes in 85 baby
boys. "We found effects at levels that are seen in a quarter of the
U.S. population," Swarm says.

But whether the malformations stem from phthalates alone or in
combination with other compounds remains unknown, because humans
encounter many chemicals in mixture. To help sort out matters, a Johns
Hopkins University study will look for the most common chemicals in
people. Umbilical cord blood will be tested for a wide array of
substances, from pesticides to phthalates to heavy metals, and the
overall levels then correlated with the babies' characteristics at
birth. Explains the study's leader, Lynn Goldman: "If we can identify
some of these mixtures to which people are commonly exposed, then
those might be the mixtures to look at more closely."