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Environmental Factor, March 2013

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Birnbaum discusses low dose at Tox Forum

By Thaddeus Schug

NIEHS/NTP Director Linda Birnbaum, Ph.D., presented a talk titled “Low Dose Exposure and NMDR [Non-Monotonic Dose Response]: Context and Implications” Jan. 30 at the 38th Annual Winter Meeting of The Toxicology Forum. During a session on non-monotonic dose, Birnbaum teamed with Kristina Thayer, Ph.D., director of the NTP Office of Health Assessment and Translation (OHAT), to explain how low dose environmental exposures can lead to adverse health outcomes.

Birnbaum gave an overview of low dose exposures, explaining that some classes of chemicals, such as endocrine disruptors, can have very different biological effects at different doses. Birnbaum made her case using examples of studies in human and animal models that illustrate adverse biological outcomes at exposure levels similar to those found in many human populations.

“We see low dose chemical effects in many normal biological processes, for example, in circulating levels of hormones, nutritional exposure to essential vitamins, and in pharmaceuticals,” she explained. “There is no reason to believe that hormone mimicking chemicals would behave any differently.”

Thayer used the opportunity to describe how OHAT plans to bring systematic review methodology and new information management tools into the group’s literature-based evaluations. According to Thayer, the systematic review process is going to be a powerful tool in helping NTP develop evidence-based conclusions in difficult topic areas, such as low dose exposures.

Meeting organizer, Tim Pastoor, Ph.D., principal scientist at Syngenta, observed that the area of non-monotonic dose-response is not new, but perspectives recently presented in an editorial published by Birnbaum in Environmental Health Perspectives challenge the fundamentals of toxicology and the regulatory testing paradigm.

The Toxicology Forum meetings primarily consist of senior regulatory scientists from government, such as the U.S. Environmental Protection Agency (EPA) and the U.S. Food and Drug Administration (FDA), and the private sector. Members of academia and non-government organizations, such as the Humane Society, often attend the event as well, and academics frequently participate.

The motto of The Toxicology Forum is "Understanding Through Dialogue." The Forum sponsors two meetings a year with topics that range from FDA and EPA regulatory issues, to scientific presentations that can include such topics as cardiac biomarkers or acrylamide exposure studies. According to Pastoor, the Forum truly seeks to foster robust scientific discourse that is open, honest, and instructive.

(Thaddeus Schug, Ph.D., is a health scientist in the NIEHS Division of Extramural Research and Training and a regular contributor to the Environmental Factor.)

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