Endocrine Disrupters: The Need for a Refocused Vision

Terri Damstra, Ph.D.

World Health Organization WHO/UNEP/ILO International Programme on Chemical Safety

Over the last two decades, concerns about the potential health and ecological impacts of exposure to endocrine disrupting chemicals (EDCs) have led to the establishment of new, multi-stakeholder research and testing initiatives, committees, expert groups, newsletters, databases, etc., throughout the world. In addition to generating an influx of new data, these activities have catalyzed a number of scientific controversies. Controversies range from how to spell, define, and detect "endocrine disrupters" to whether adverse effects observed in wildlife and humans are due to EDC exposures (at levels found in general populations) or other causes. Despite a lack of scientific consensus, this tidal wave of activity has significantly advanced our understanding of the scope and magnitude of risks posed by EDCs. Nevertheless, as the perceptive article by Daston et al. (2003; this issue)Go indicates, many genuine uncertainties remain and key questions continue to go unanswered.

The recent "Global Assessment of the State-of-the-Science of Endocrine Disruptors" (Damstra et al., 2002Go), published (with input from over 60 independent, international scientific experts) by the WHO/UNEP/ILO International Programme on Chemical Safety (IPCS), concluded that:

Overall the biological plausibility of possible damage to certain human functions; (particularly reproductive and developing systems) from exposure to EDCs seems strong when viewed against the background of known influences of endogenous and exogenous hormones on many of these processes. Furthermore, the evidence of adverse outcomes in wildlife and laboratory animals exposed to EDCs substantiates human concerns. The changes in human health trends in some areas for some outcomes are also sufficient to warrant concern and make this area a high research priority, but non-EDC mechanisms also need to be explored. (Damstra et al., 2002Go, p. 3)

In addition to its global perspective, the WHO assessment was unique in that it developed a weight-of-evidence framework utilizing objective criteria to evaluate causality between exposure to EDCs and particular health outcomes.

Why then, despite a wealth of scientific expertise and enthusiasm, and an estimated 150 million U.S. dollars devoted annually to EDC-related research and testing programs globally, is there continuing uncertainty, controversy, and lack of scientific consensus? My personal view is that in a number of cases, past EDC-related research suffered from "blurred" vision, which can lead to distorted interpretations of the data. Now is an opportune time for a vision check and a new pair of lenses. I propose that, at minimum, our refocused vision needs the following characteristics:

  1. Far-sighted focus. There is a need to be patient and to avoid overinterpretation of the data. Given the complex, interactive nature of the endocrine system, it is extremely unlikely that a single set of studies, research strategy, or test battery will provide definitive answers. Uncertainty in data from studies on complex phenomena does not imply poor quality of data. Some questions may only be answered by complex, expensive, large population-based studies, and it may take a long time to get adequate data.
  2. Sharpened focus on exposure issues. Worldwide—despite large expenditures of money, time, and effort—lack of adequate exposure data on EDCs continues to be the weakest link in assessing exposure-response effects. Of particular concern is the lack of exposure data on levels, timing, and duration of exposure relative to the developmental stage of the organism. Focusing on the "timing of the dose" may be more important than the "level of the dose." Until global, coordinated, and comparable exposure data sets, specifically designed to address EDCs at different life stages, become available, credible risk assessments of EDCs cannot be performed.
  3. Increased depth perception. The need for far-sighted vision does not negate the fact that much useful data can be obtained by taking a complex system apart and analyzing its individual components. EDCs are known to act at multiple sites through multiple modes of action, but for most putative exposure-response relationships, the mechanisms of action are poorly understood. Mechanistic data on all components of endocrine-mediated pathways are critical for establishing causal associations and developing adequate test methods for EDCs.
  4. Multifocal, progressive vision. In order to see the complete picture, data is needed to fill the huge gaps in our knowledge of the biological processes and tissue responses that occur between early molecular events (e.g., gene expression) and the ultimate health outcome. These processes are not driven by the independent actions of a few causal factors, but are multifactorial and interconnected. There are likely no clear demarcation lines, which will make causal relationships far from direct or linear.

In summary, studies on EDCs need to focus on many components at many different levels. Multilevel, multidisciplinary approaches can lead to insights not possible from narrow viewpoints. Only through a weight-of-evidence approach will we be able to address causal associations of exposure to complex mixtures of contaminants to health outcomes (which are often subtle, and may take years to develop). The challenges facing the international research, industry, and regulatory community in assessing risks posed by EDCs are enormous and require the commitment, expertise, and resources available throughout the world.

The WHO/UNEP/ILO IPCS is committed to a continuing evaluation of scientific developments in this field, to addressing the global implications of the data, and to promoting international collaboration and coordination.

REFERENCES

Damstra, T., Barlow, S., Bergman, A., Kavlock, R., and Van der Kraak, G. (2002). Global Assessment of the State-of-the-Science of Endocrine Disruptors. WHO publication no. WHO/PCS/EDC/02.2. World Health Organization, Geneva, Switzerland.

Daston, G., Cook, J. C., and Kavlock, R. J. (2003). Uncertainties for endocrine disrupters: Our view on progress. Toxicol. Sci. 74(2), 245–252.





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