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<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><span style="font-size:12.0pt"><a href="http://www.environmentalhealthnews.org/ehs/news/2015/apr/diabetes-fish-endocrine-disruption-hormones-metformin">http://www.environmentalhealthnews.org/ehs/news/2015/apr/diabetes-fish-endocrine-disruption-hormones-metformin</a></span><o:p></o:p></font></p>
<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><o:p> </o:p></font></p>
<p class="MsoNormal"><font size="5" color="#333333" face="Times New Roman"><span style="font-size:17.0pt;color:#333333">Exposure to widespread diabetes drug feminizes male fish<o:p></o:p></span></font></p>
<p class="MsoNormal"><font size="5" color="#333333" face="Times New Roman"><span style="font-size:17.0pt;color:#333333"><o:p> </o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><i><font size="5" color="#333333" face="Helvetica"><span style="font-size:18.0pt;font-family:"Helvetica","sans-serif";color:#333333;font-style:italic">Exposure to metformin, a first-line treatment for type-2
diabetes, feminizes male minnows and impacts fertility at levels common in wastewater effluent.</span></font></i><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">April 28, 2015<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">By
<a href="http://www.environmentalhealthnews.org/archive?text=&start_date=&end_date=&publisher=&reporter=Brian+Bienkowski&article_type=&subject=">
<font color="#428bca"><span style="color:#428BCA;text-decoration:none">Brian Bienkowski</span></font></a><br>
Environmental Health News<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">Male minnows exposed to a widely used diabetes drug ubiquitous in wastewater effluent
had feminized reproductive parts and were smaller and less fertile, according to a
<a href="http://www.sciencedirect.com/science/article/pii/S0045653515002830%20%20%20%20%20">
<font color="#428bca"><span style="color:#428BCA;text-decoration:none">new study</span></font></a>.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><img border="0" width="405" height="182" id="Picture_x0020_1" src="cid:image001.jpg@01D081D2.1D0F1F70" alt="http://www.environmentalhealthnews.org/ehs/images/2015/ehn-and-tdc/april/metformin/fathead2.jpg/"></span></font><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
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<font size="1" color="#999999" face="Helvetica"><span style="font-size:6.5pt;font-family:"Helvetica","sans-serif";color:#999999"><a href="http://wildlife.ohiodnr.gov/species-and-habitats/species-guide-index/fish/fathead-minnow"><font size="1" color="#999999"><span style="font-size:5.0pt;color:#999999;text-decoration:none">Ohio
DNR</span></font></a><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt;line-height:12.0pt"><font size="1" color="#555555" face="Helvetica"><span style="font-size:6.0pt;font-family:"Helvetica","sans-serif";color:#555555">Developing male fathead minnows were feminized by exposure to
metformin.</span></font><font size="1" color="#555555" face="Helvetica"><span style="font-size:7.0pt;font-family:"Helvetica","sans-serif";color:#555555"><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">“Normally in females you see eggs developed in ova, in males, you see a different
structure – producing tiny sperm instead of an egg structure,” said Rebecca Klaper, an associate professor at the University of Wisconsin-Milwaukee and senior author of the study. “We saw development of larger egg structures within the [male’s] testis.”<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">Pharmaceutical chemicals are ubiquitous in wastewater effluent. Researchers estimate
that, by mass, metformin is among the <a href="http://www.ncbi.nlm.nih.gov/pubmed/23183121">
<font color="#428bca"><span style="color:#428BCA;text-decoration:none">most common pharmaceutical</span></font></a> in wastewater.
<br>
<br>
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.<o:p></o:p></span></font></p>
<p class="MsoNormal"><b><font size="1" color="#057234" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#057234;font-weight:bold">"Normally in females you see eggs developed in ova, in males, you see a different structure
— producing tiny sperm instead of an egg structure. We saw development of larger egg structures within the [male's] testis."
</span></font></b><b><i><font size="1" color="#057234" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#057234;font-weight:bold;font-style:italic">-Rebecca Klaper, University of Wisconsin-Milwaukee</span></font></i></b><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><img border="0" width="225" height="277" id="Picture_x0020_2" src="cid:image002.jpg@01D081D2.1D0F1F70" alt="http://www.environmentalhealthnews.org/ehs/images/2015/ehn-and-tdc/april/metformin/Klaper.jpg/"></span></font><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
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<font size="1" color="#999999" face="Helvetica"><span style="font-size:6.5pt;font-family:"Helvetica","sans-serif";color:#999999"><a href="http://uwm.edu/freshwater/people/"><font size="1" color="#999999"><span style="font-size:5.0pt;color:#999999;text-decoration:none">University
of Wisconsin-Milwaukee</span></font></a><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt;line-height:12.0pt"><font size="1" color="#555555" face="Helvetica"><span style="font-size:6.0pt;font-family:"Helvetica","sans-serif";color:#555555">Rebecca Klaper</span></font><font size="1" color="#555555" face="Helvetica"><span style="font-size:7.0pt;font-family:"Helvetica","sans-serif";color:#555555"><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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
<a href="http://www.usgs.gov/newsroom/article.asp?ID=3921#.VT9n1GRVhHw%20"><font color="#428bca"><span style="color:#428BCA;text-decoration:none">researchers reported</span></font></a> intersex fish in Pennsylvania’s Susquehanna, Delaware and Ohio river basins,
suggesting that estrogenic chemicals were to blame. <o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">“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.”<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><img border="0" width="405" height="270" id="Picture_x0020_3" src="cid:image003.jpg@01D081D2.1D0F1F70" alt="http://www.environmentalhealthnews.org/ehs/images/2015/ehn-and-tdc/april/metformin/effluent.jpg/"></span></font><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
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<font size="1" color="#999999" face="Helvetica"><span style="font-size:6.5pt;font-family:"Helvetica","sans-serif";color:#999999"><a href="http://www2.humboldt.edu/arcatamarsh/currentperformance3.html"><font size="1" color="#999999"><span style="font-size:5.0pt;color:#999999;text-decoration:none">Humboldt.edu</span></font></a><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt;line-height:12.0pt"><font size="1" color="#555555" face="Helvetica"><span style="font-size:6.0pt;font-family:"Helvetica","sans-serif";color:#555555">Metformin gets into wastewater effluent when people excrete
it. It's one of the most common pharmaceuticals found in effluent. </span></font><font size="1" color="#555555" face="Helvetica"><span style="font-size:7.0pt;font-family:"Helvetica","sans-serif";color:#555555"><o:p></o:p></span></font></p>
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<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">“It’ll be worth finding out if its transformation product also has these bioactive
properties,” Kolpin said.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">The U.S. Environmental Protection Agency’s latest
<a href="http://www.gpo.gov/fdsys/pkg/FR-2015-02-04/html/2015-02210.htm"><font color="#428bca"><span style="color:#428BCA;text-decoration:none">drinking water contaminant candidate list</span></font></a> — 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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333">“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.<o:p></o:p></span></font></p>
<p class="MsoNormal" style="margin-bottom:6.0pt"><i><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333;font-style:italic">EHN welcomes republication of our stories, but we require
that publications include the author's name and Environmental Health News at the top of the piece, along with a link back to EHN's version.</span></font></i><font size="1" color="#333333" face="Helvetica"><span style="font-size:8.5pt;font-family:"Helvetica","sans-serif";color:#333333"><o:p></o:p></span></font></p>
<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><o:p> </o:p></font></p>
<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><o:p> </o:p></font></p>
<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><o:p> </o:p></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Times New Roman"><span style="font-size:10.0pt;color:navy">Deborah L. DeBiasi</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><b><font size="2" color="navy"><span style="font-size:10.0pt;color:navy;font-weight:bold">Email: Deborah.DeBiasi@deq.virginia.gov</span></font></b><b><i><font size="2" color="red"><span style="font-size:10.0pt;color:red;font-weight:bold;font-style:italic"><br>
</span></font></i></b><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">WEB site address:
<a href="http://www.deq.virginia.gov/">www.deq.virginia.gov</a></span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">Virginia Department of Environmental Quality</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">Office of Water Permits
</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">Industrial Pretreatment/Whole Effluent Toxicity (WET) Program</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">PPCPs, EDCs, and Microconstituents<o:p></o:p></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Times New Roman"><span style="font-size:11.0pt;color:navy"><a href="http://www.deq.virginia.gov/Programs/Water/PermittingCompliance/PollutionDischargeElimination/Microconstituents.aspx">http://www.deq.virginia.gov/Programs/Water/PermittingCompliance/PollutionDischargeElimination/Microconstituents.aspx</a></span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy"><o:p></o:p></span></font></p>
<p class="MsoNormal"><font size="2" color="navy" face="Times New Roman"><span style="font-size:10.0pt;color:navy">Mail: P.O. Box 1105, Richmond, VA 23218</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">Location: 629 E. Main Street, Richmond, VA 23219</span></font><font size="2" color="navy"><span style="font-size:11.0pt;color:navy"><br>
</span></font><font size="2" color="navy"><span style="font-size:10.0pt;color:navy">PH: 804-698-4028 FAX: 804-698-4032<o:p></o:p></span></font></p>
<p class="MsoNormal"><font size="3" color="#000099" face="Times New Roman"><o:p> </o:p></font></p>
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