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European Teratology Society honors NIEHS-led research

By Melissa Kerr
October 2010

NIEHS Staff Scientist Retha Newbold
Principal Investigator Newbold is a veteran NIEHS researcher and a pioneer in the research of endocrine disrupting compounds in the environment and their effects on human health and development. (Photo courtesy of Steve McCaw)

A study funded by an interagency agreement between NIEHS and the U.S. Food and Drug Administration (FDA) was honored as Paper of the Year at the European Teratology Society (ETS) annual conference Sept. 5-8 in Barcelona, Spain.

NIEHS Staff Scientist Retha Newbold was principal investigator and senior author on the study ( Exit NIEHS. First author Barry Delclos, Ph. D., an FDA National Center for Toxicological Research (NCTR) pharmacologist, presented an Elsevier Award lecture based on the research.

The Elsevier Award is an honor given to authors of the paper selected by ETS council members as the best paper published in the journal Reproductive Toxicology ( Exit NIEHS the previous year.

Expanding on research initiated by the National Toxicology Program (NTP), the study examined multiple generations and collected data on chronic toxicity and reproductive effects of exposure to genistein and ethinyl estradiol (EE2). The study was an effort to address aspects of the endocrine disruptor hypothesis, which emerged from work on diethylstilbestrol (DES), a synthetic estrogen that is well established as a cause of several adverse affects in both sexes, including carcinogenesis.

According to the endocrine disruptor hypothesis, there are other chemicals in the environment that are weaker estrogens than DES, but could still have the potential to cause similar adverse effects in both human and wildlife populations.

Genistein is a phytoestrogen found commonly in soy-based foods, dietary supplements and infant formulas. EE2 is a bio-active estrogen used in almost all modern oral contraceptive pill formulas and is also found as an environmental contaminant. The experiments spanned five generations and compared the similar and different adverse effects observed by feeding the test subject the two different chemicals at several dose levels.

According to the study report, both EE2 and genistein in high doses showed similar effects in continuously exposed female rats, "including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals." Genistein-treated animals showed a reduction in litter size, while EE2 significantly increased the occurrence of uterine lesions. The offspring of succeeding generations of exposed animals also showed some of the effects. The relevance of the findings to human exposure situations is unknown at this point.

It was the first time Delclos had attended the annual meeting. "I found it to be an interesting meeting," he said, "conductive to open discussion and exchange of ideas." According to the Society's Website, the objectives of ETS are to stimulate interest in and promote the sharing of ideas and information about the causes and prevention of adverse effects on reproduction and development. The conference, held in conjunction with the European Network of Teratology Information Services (ENTIS), explored the causes and prevention of birth defects in Europe.

Delclos said he enjoyed working with and learning from Newbold. He explained, "The most important thing to me [about the award] is that the hard work of the many individuals involved in the planning and conduct of these studies, both here at NCTR and at NTP, was acknowledged."

Citation: Delclos KB, Weis CC, Bucci TJ, Olson G, Mellick P, Sadovova N, Latendresse JR, Thorn B and Newbold RR. ( Exit NIEHS 2009. Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies. Reprod Toxicol 27(2):117-132.

(Melissa Kerr studies chemistry at North Carolina Central University. She is currently an intern in the NIEHS Office of Communications and Public Liaison.)

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