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Environmental Factor, March 2013

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BPA grantees share findings

By Robin Mackar

Linda Birnbaum, Ph.D.

Birnbaum cleared her busy schedule to spend two full days with the grantees and invited speakers. She listened to the discussions and presented some data from her own studies. (Photo courtesy of Steve McCaw)

Tracey Woodruff, Ph.D. and Laura Vandenberg, Ph.D.

There were some lively discussions among the attendees, following the update on the BPA round-robin testing of human blood levels by Vandenberg, left, and Woodruff. (Photo courtesy of Steve McCaw)

Gail McCarver, M.D.

Gail McCarver, M.D., of the Medical College of Wisconsin, listened to research being presented by others working on BPA. McCarver also collaborates and advises both NIEHS and NTP on many other environmental health issues. (Photo courtesy of Steve McCaw)

Joseph Braun, Ph.D. and Antonia Calafat, Ph.D.

Joseph Braun, Ph.D., of Brown University, left, consulted with Antonia Calafat, Ph.D., a biomonitoring expert at the Centers for Disease Control and Prevention. (Photo courtesy of Steve McCaw)

Nearly 100 researchers studying the health effects of the chemical bisphenol A (BPA) gathered at NIEHS Jan. 28-29 to provide an update on their findings. Many were presenting the final data from funding they received through the American Recovery and Reinvestment Act.

“We’ve invested well over $30 million on BPA in the past few years, and we are here today partially to bask in our research accomplishments, but also to talk about the issues we really need to work on as we move forward,” NIEHS/NTP Director Linda Birnbaum, Ph.D., said, as she kicked off the meeting organized by Jerry Heindel, Ph.D., and Thaddeus Schug, Ph.D., of the NIEHS Division of Extramural Research and Training (DERT).

The one-NIEHS approach to BPA

After the official welcome and meeting kickoff, Birnbaum presented an overview of the big picture, one-NIEHS strategic approach that the Institute has been taking to assess the health effects of bisphenol A.

“At NIEHS, we have developed an unprecedented, comprehensive research program that combines extramural grant funding with targeted intramural research efforts and outside collaborations, to help fill research gaps and provide results that will help inform regulatory decision-making,” Birnbaum said proudly, detailing many of the points made by her and her colleagues in an Environmental Health Perspectives commentary.

BPA biomonitoring and pharmacokinetics

During the morning’s biomonitoring topic session, Tracey Woodruff, Ph.D., and Roy Gerona, Ph.D., from the University of California, San Francisco teamed with Laura Vandenberg, Ph.D., of Tufts University, to give an update on the status of the round-robin experiments that NIEHS has been supporting to help determine the most accurate way to measure BPA levels in human serum.

The round-robin experiment includes having members of the BPA Grantee Consortium, from five laboratories, measure, analyze, and interpret BPA levels in a variety of NTP blood samples, to determine if the labs can get similar results. Woodruff reported that the labs are completing the third round of blind testing and results should be available soon.

“We are hoping to identify a preferred protocol that can reliably measure BPA in serum, and can eliminate potential contamination and other sources of error among various labs,” Vandenberg said.

Also during the biomonitoring session, Birnbaum and others, including grantee Fred vom Saal, Ph.D., of the University of Missouri, presented updates on ongoing studies looking at exposure to BPA through routes other than diet, including through the skin. For example, BPA and BPA alternatives are often used in some cash register receipts and may contribute to BPA exposure levels.

The session concluded with a presentation from one of France’s leading experts on BPA pharmacokinetics, Pierre-Louis Toutain, D.V.M., Ph.D., who illustrated the similarities of ingested BPA across species.

Disease endpoints

Much of the rest of the meeting was spent hearing from grantees who have been working on various diseases endpoints that may be related to BPA.

Overall, the grantees’ recent work continues and expands many of their earlier findings that showed that early life exposures to BPA, in animal studies, can lead to a variety of diseases or health problems into adulthood. Adult diseases with a fetal basis under consideration include prostate cancer, breast cancer, obesity, diabetes, cardiovascular problems, and some neurobehavioral conditions, such as anxiety, as well as reproductive disorders. The animal literature seems to support outcomes now being found in some human studies.

“The findings are suggesting that individual susceptibility to BPA may be at play,” Birnbaum said, after hearing all the presentations. “BPA may have different effects in different people, [and] those more susceptible to it may experience adverse health effects later in life. Our primary concern related to BPA continues to be during prenatal development.”

(Robin Mackar is the news director in the NIEHS Office of Communications and Public Liaison, and a frequent contributor to the Environmental Factor.)

Caren Weinhouse and Almudena Veiga-Lopez, D.V.M, Ph.D.

Poster presentations at the meeting offered additional opportunities for people to talk science. University of Michigan (UM) Ph.D. candidate Caren Weinhouse, right, described some of her early exposure research findings to UM colleague Almudena Veiga-Lopez, D.V.M, Ph.D., who specializes in endocrine disruption. (Photo courtesy of Steve McCaw)

Julius Thigpen, Ph.D. and Tristan Nicholson

Julius Thigpen, Ph.D., formerly with the Comparative Medicine Branch at NIEHS, listened to most of the discussions at the meeting and spent some quality time talking to the students and grantees working on BPA, including Tristan Nicholson of the University of Wisconsin. (Photo courtesy of Steve McCaw)

Heindel, Aungst, Husoy, and Teeguarden

Heindel, left, who oversees much of the NIEHS BPA grants portfolio and served as the lead organizer for the third annual meeting of the BPA consortium, made the rounds at the meeting, talking to everyone, including, left to right, FDA scientist Jason Aungst, Ph.D.; European Food Safety Authority representative Trine Hus√ły, Ph.D.; and NIEHS grantee Justin Teeguarden, Ph.D., of the Pacific Northwest National Laboratory. (Photo courtesy of Steve McCaw)

Jerry Heindel, Ph.D. and Thomas Zoeller, Ph.D.

Heindel, right, talked to grantee Thomas Zoeller, Ph.D., of University of Massachusetts Amherst about his work on BPA and thyroid signaling during one of the meeting breaks. (Photo courtesy of Steve McCaw)

Bringing CLARITY to BPA

Luisa Camacho, Ph.D., of the U.S. Food and Drug Administration (FDA) National Center for Toxicological Research (NCTR), presented an update on the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY–BPA) research program.

CLARITY-BPA is an unprecedented collaboration that brings together academic researchers with federal regulators to answer critical research questions that will help inform regulatory decision-making.

The collaboration calls upon the expertise of NTP, DERT, and FDA to conduct a BPA toxicity study in rats at NCTR, in accordance with established good laboratory practices (GLP). The strain on the animal, the animal’s diet and housing conditions, the number of animals, the dosing regimen, and the route of exposure of BPA are all tightly controlled.

Twelve NIEHS-supported grantees are also participating in the study. The grantees were selected through a competitive review process for their expertise on various disease endpoints and have been heavily involved in designing the protocols for the GLP study. The grantees will also have access to tissue samples and laboratory animals from the GLP-compliant study, drawing upon their areas of expertise to study a range of health endpoints, including male and female reproduction; uterine, mammary, and prostate cancer; metabolic effects; neurological and neurobehavioral effects; and immune function.

The study uses a broad range of BPA doses to look at effects across two generations.

“This is quite an endeavor that we’ve undertaken,” Heindel said in amazement, as he looked at a slide depicting the labor-intensive dosing schedule that NCTR is managing. “It’s really a new way of doing science that should help answer a lot of questions.”

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