NIEHS experts speak at EU Conference on Endocrine Disruptors
By Eddy Ball
NIEHS/NTP Director Linda Birnbaum, Ph.D., opened the European Union (EU) Conference on Endocrine Disruptors June 11 in Brussels with her keynote presentation on “Endocrine Disruption: Where Do We Go From Here?” The conference, which was sponsored by the European Commission, attracted more than 350 attendees.
Joining Birnbaum in the program’s exploration of current challenges and policy were NIEHS Health Scientist Administrator Jerry Heindel, Ph.D., and grantee Tracey Woodruff, Ph.D., as well as researchers and policy experts from the U.S. and EU. The NIEHS representatives were also panelists in a moderated discussion of issues related to endocrine disrupting chemicals (EDCs).
Understanding diseases with an environmental component
Birnbaum opened her talk by presenting her comprehensive definition of environment and placing endocrine disruption in the larger context of diseases with a known or suspected environmental component. She explained that environment is an important part of the matrix of disease causation, and emphasized the importance of indirect or delayed effects of exposure in shaping the endocrine signals that govern every organ and process in the body, as well as the frank manifestation of physiological harm, which classic toxicology calls apical endpoints.
“The main point here is that death or cancer are not the only endpoints that are important when considering environmental health,” she explained. “Reproductive function, brain development, lung function, and other physiological properties rely on proper development in order to maintain health, and environmental stressors can affect each of these functions.”
The presentation featured several detailed slides, including a schematic of the effects of insulin in tissue, underscoring the complexity and vulnerability of the endocrine system to EDC exposure in its many points of regulation and control. Birnbaum explained that EDCs are ubiquitous in the environment, occurring in a host of widely used pesticides and industrial chemicals. They can have a wide range of effects on health at low doses, especially when exposure occurs during windows of susceptibility in the course of development, she said.
Looking ahead, Birnbaum described the potential of Tox21, and other high-throughput, screening-based predictive toxicology efforts, in more comprehensively identifying potential EDCs and discovering new, relevant endocrine endpoints. She called for more research into mixtures, a sharper focus on public health, and the development of effective regulatory policy to help prevent disease.
Re-thinking dose response with EDCs
While Birnbaum’s talk had been a survey of EDCs, Heindel’s presentation focused on the characteristics and principles that convince him EDCs should be assessed according to different criteria than are used with most toxic substances. The basis of his argument was that the endocrine system functions according to distinct principles, and that, by implication, EDCs should be assessed according to six endocrine-specific principles:
- Hormones control everything in the human body, with multiple target tissues and organs, as distant from each other as the hypothalamus and the skeletal muscle in the lower extremities.
- Hormones act through tissue-specific receptors that can become saturated as doses increase.
- Hormones act at very low doses, as small as a few parts per trillion.
- Hormones regulate their own receptors, making the dose response more complex than it is with other toxic substances, because of the potential for saturating receptors.
- Due to overlapping pathways, hormones produce a non-typical dose-response curve, known as monotonic, which allows for decreases in the effect at some doses and increases at others.
- Hormonal action is life-stage specific, with tissue- and time-specific effects that are most harmful during development, leading to increased disease risk later in life.
Heindel closed by posing the question he anticipates will drive discussion in future efforts to better understand endocrine toxicology, “Are there sufficient data to incorporate low dose and non-monotonic responses and new endocrine endpoints into risk assessment?” An upcoming workshop (http://tools.niehs.nih.gov/conference/dert_endocrine_2012/) Sept. 11-13 in Berlin, co-sponsored by NIEHS, will address that very issue, with an assessment of low-dose data and data needs for defining a path forward.
Moving forward with the EU community strategy for endocrine disruptors
Presentations and discussions at the conference explored the effects of endocrine disruptors on human health and the environment, the risks, the identification of endocrine disruptors, and policy objectives. Along with a report commissioned by the Directorate-General for the Environment in 2009 and published this year, “State of the Art of the Assessment of Endocrine Disrupters,” the outcome of the conference will feed into the review of the European Commission's current strategy on endocrine disruptors. It will also provide input to the Commission's upcoming proposal for criteria for the identification of substances with endocrine disrupting properties.
The EU “Community Strategy for Endocrine Disrupters,” first published in 1999, focused on short, medium, and long-term actions that, when implemented, would contribute to ensuring a better environment and health for people within the EU. The European Commission has supplemented the original strategy document with a series of implementation documents refining proposed actions.