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NIEHS Director Gives Distinguished Lecture

By Robin Arnette
October 2009

Birnbaum speaking to a near-capacity audience in the Institute's Rodbell Auditorium.
Birnbaum spoke to a near-capacity audience in the Institute's Rodbell Auditorium. Along with employees of NIEHS and NTP, attendees included visitors from the U.S. Environmental Protection Agency and other organizations in the area. (Photo courtesy of Steve McCaw)

Lecture host Michelle Hooth [Right]
Seated behind one of several outside visitors drawn to NIEHS by Birnbaum's talk was lecture host Michelle Hooth, right. Hooth is a member of the NTP Toxicology Branch and Women Scientist Assembly co-advisor. (Photo courtesy of Steve McCaw)

Matthew Longnecker, M.D., Sc.D., [Right] and Michelle Heacock, Ph.D.
NIEHS Intramural epidemiologist Matthew Longnecker, M.D., Sc.D., right, and structural biologist Michelle Heacock, Ph.D., joined Extramural science administrators Pat Mastin, Ph.D., and Beth Anderson, left, for the talk, which had a cross-divisional appeal. (Photo courtesy of Steve McCaw)

NIEHS and National Toxicology Program (NTP) Director Linda Birnbaum, Ph.D., D.A.B.T., A.T.S.(http://www.niehs.nih.gov/about/od/director/index.cfm), presented the first seminar of the 2009 - 2010 NIEHS Distinguished Lecture Series on September 8 titled "Halogenated Flame Retardants: Does the Benefit Justify the Risk?" The lecture focused on halogenated flame retardants (HFRs), particularly brominated flame retardants (BFRs), which are widely used in consumer products to reduce fire-related injury and property damage. Birnbaum, a board-certified toxicologist who has spent several years of her research career studying these toxic chemicals, suggested that their health and environmental effects may outweigh their fire-prevention benefits.

Introducing the speaker was NTP toxicologist Michelle Hooth, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/tob/hooth/index.cfm), who represented the lecture host, the NIEHS Women's Scientist Assembly (WSA).

According to Birnbaum, HFRs are heavily used in electronics, building and wire insulation, polyurethane foam, carpet padding, computer casings and televisions, just to name a few. Although there are many classes of HFRs, she said that BFRs are the largest class because they are cheap and extremely effective. One of these brominated molecules, tetrabromobisphenol A (TBBPA), doesn't escape into the environment easily because it chemically binds with the product matrix, but when the matrix does break down, it could have devastating consequences. "TBBPA can eventually generate bisphenol A (BPA), and we all know about BPA and its endocrine disrupting properties," Birnbaum said.

She also discussed another concern regarding TBBPA. "When TBBPA burns, it generates brominated dioxins. TBBPA also disturbs the homeostasis of the thyroid system," she explained. "It does so by binding with a higher affinity to transthyretin, a major thyroid transport protein in mammals, than to the natural ligand T4. This process could interrupt a key step during development in rodents and humans."

Birnbaum's current studies involve hexabromocyclododecane (HBCD), another BFR that poses a threat to wildlife. Since HBCD is mixed with the product matrix rather than being bound to it chemically, HBCD easily escapes into the environment. In vitro studies have demonstrated that HBCD is an anti-androgen and an aromatase inhibitor, specifically binding to several steroid hormone receptors.

The commercial mix of HBCD is composed of three stereoisomers, alpha, beta and gamma, with gamma making up 70 - 80 percent of the mixture. Birnbaum and her colleagues noticed that soil sediments from a particular location tended to resemble the commercial mix, but the biota - the plants and animals living in that environment - had more of the alpha isomer than gamma. The phenomenon, known as an HBCD diasteriomer shift intrigued Birnbaum, and she wanted to understand what was happening.

"Our collaborators labeled alpha and gamma with 14C, and we did a dose-dependent study in which we exposed mice to a single dose and looked at the elimination," she explained. "With gamma there is no dose effect in elimination, but much less alpha is coming out in the urine than gamma, which suggests that alpha is more persistent."

Birnbaum ended her talk with polybrominated diphenyl ethers (PBDEs), compounds that changed behaviors and caused deficits in cognitive and sensory function in rat and mouse studies. Since many products contain PBDEs, people in the U.S. and U.K., for example, are exposed to the chemical through the air and dust in their homes and offices. However, these groups may not be at the highest risk.

"Kids in poor countries who live and work in garbage dumps have the highest levels of PBDE, and these levels are comparable to the upper five percent of the American population," Birnbaum noted. She concluded by saying that researchers must find an alternative for HFRs. The material should have low toxicity and minimize the potential for hazard and exposure.

Hooth commented afterwards that the information Birnbaum presented helped those in the audience who were not toxicologists better understand the field. "Dr. Birnbaum's lecture highlighted a number of principal concepts in toxicology, including the importance of evaluating low dose effects, the metabolism and distribution of compounds, sensitive life stages and a variety of relevant endpoints."

(Note: This issue also includes a story (http://www.niehs.nih.gov/news/newsletter/2009/october/spotlight-beijing.cfm) about Birnbaum's talk at the August 22 Green Science Policy Symposium on "The Fire Retardant Dilemma in China.")



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