I'm sure glad I'm not a minnow |
It
is the first study to examine the drug metformin’s impact on fish endocrine
systems and suggests that non-hormone pharmaceuticals pervasive in wastewater
may cause reproductive and development problems in exposed fish.
Metformin
is largely used to combat insulin resistance associated with type-2 diabetes,
which accounts for about 90 percent of all diagnosed U.S. adult diabetes cases.
Researchers
from the University of Wisconsin-Milwaukee exposed young fathead minnows to
water containing levels of metformin commonly found in wastewater effluent.
Eighty-four percent of 31 metformin-exposed male fish exhibited feminized
reproductive organs.
A
couple of non-exposed males had very minor feminization, but signs of egg
development were nothing compared to what happened in the exposed fish, Klaper
said. In addition to the feminization, exposed male minnows weighed less
and had significantly less babies when they reproduced, suggesting that the
feminization may impact their ability to reproduce properly.
Pharmaceutical
chemicals are ubiquitous in wastewater effluent. Researchers estimate that, by
mass, metformin is among the most
common pharmaceutical in wastewater.
More
than nine percent of the U.S. population has diabetes, according to the Centers
for Disease Control and Prevention. The agency estimates that from 1980 to
2011, cases of diagnosed diabetes almost tripled.
Increased
illnesses means more drugs. Pharmaceutical drugs get into our wastewater when
people flush their medication or, more commonly, when they excrete them.
Metformin, unlike many pharmaceutical drugs, is not metabolized by the human
body, and gets excreted unchanged.
Metformin’s
“really been hitting people’s radar more of late,” said Dana Kolpin, a U.S.
Geological Survey research hydrologist based in Iowa and project chief of the
agency’s emerging contaminants project. Kolpin said as water testing methods
have gotten more sophisticated, metformin seems to be one of the most
frequently detected. “It’s persistent and mobile,” he said.
Scientists
have expressed concern that birth control and other hormone mimicking drugs in
water could impact fish populations and cause feminization. Last year U.S.
Geological Survey researchers reported intersex
fish in Pennsylvania’s Susquehanna, Delaware and Ohio river basins, suggesting
that estrogenic chemicals were to blame.
However,
metformin is not an estrogenic or hormone-mimicking drug. Rather it is designed
to improve insulin sensitivity. It appears a “nontraditional endocrine
disrupting chemical,” Klaper and her University of Wisconsin-Milwaukee
colleague, Nicholas Niemuth, wrote in the study published in the journal
Chemosphere.
While
researchers are not totally clear how the drug disrupts fish hormones,
metformin has been shown to alter the activity of certain enzymes that are
involved in hormone pathways.
“We
know from some vertebrate studies that insulin and metabolism in an organism is
tied into reproduction,” Klaper said. “But how metformin would cause a
difference in actual egg production is something we don’t know but is very
interesting. Now we’re trying to figure out why.”
Klaper
previously found that metformin caused some signs of endocrine disruption when
she exposed adult fish to the drug for 28 days. However, no intersex tissue was
found, suggesting that exposure during development might be the major concern.
It’s
not clear if all fish would react to metformin exposure as the fathead minnows
did, Kolpin said. Klaper said the development of male and female fish is not
entirely the same across species. She said they would continue testing fathead
minnows and also look at zebrafish to see if they exhibit similar impacts.
Kolpin
said some waterways also have been shown to have a metformin transformation
compound, called guanylurea, which is formed when metformin comes in contact with
bacteria such as in sewage.
“It’ll
be worth finding out if its transformation product also has these bioactive
properties,” Kolpin said.
The
U.S. Environmental Protection Agency’s latest drinking water contaminant candidate list —
water pollutants not subject to regulations yet but that might render water
unsafe — includes several pharmaceuticals that act on hormones. Metformin is
not on the list, published in February.
Klaper
and Niemuth wrote that metformin would probably not show up as an endocrine
disruptor under the current testing used by the U.S. EPA Agency, which relies
on the binding of chemicals to hormone receptors. Structurally, metformin
doesn’t resemble hormones. The results, they argue, suggest the EPA should
broaden its testing.
“Given
its environmental persistence and presence worldwide, this compound merits
further research on its potential environmental impacts as well as its impacts
on vertebrate development more generally and should be added to the list of
potential EDCs [endocrine disrupting chemicals],” Klaper and Niemuth wrote.