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Environmental Factor, October 2012

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Low dose experts gather in Berlin

By Thaddeus Schug

Potential low dose health effects

Endocrine signals govern every organ and process in the body.  This means that when chemicals interfere with endocrine signaling, the effects can be seen in many different conditions and diseases. (Photo courtesy of Jerry Heindel)

Non-monotonic dose respons

Heindel used the diagram in his presentation. “Some agents, such as endocrine disruptors, have a substantial impact on our health even at very low doses,” he explained. “For some endocrine disruptors, biological changes can be seen at low doses, but not at high doses.” (Photo courtesy of Jerry Heindel)

NIEHS/NTP Director Linda Birnbaum, Ph.D., welcomed risk assessors, toxicologists, endocrinologists, and epidemiologists to the “Low Dose Effects and Non-Monotonic Dose Responses for Endocrine Active Chemicals: Science to Practice” workshop Sept. 11 in Berlin with a video presentation. The workshop was co-organized by NIEHS Health Scientist Administrator Jerry Heindel, Ph.D., and Sharon Munn, European Commission Joint Research Centre and Institute of Health and Consumer Protection (JRC-IHCP) representative, along with a committee of scientists from U.S. and European government agencies.

“One of the environmental factors that NIEHS is investing significant resources in is research on endocrine disruptors. We want to be sure that the high quality data generated by our in-house researchers and our grantees, is useful in the risk assessment process,” said Birnbaum. “We are very interested in your views as to the strength of the data supporting low dose effects and non-monotonic dose responses for chemicals with endocrine disrupting properties,” added Birnbaum 

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Birnbaum noted that an increasing number of studies suggest that low doses are unsafe, even for populations who are not usually considered vulnerable. “Studies continue to show associations between the concentrations of these chemicals in the general population and adverse health effects, such as obesity, type-2 diabetes, reduced fertility, neurobehavioral disorders, and immune dysfunction,” she told the audience.

State of the science on endocrine-active substances

The workshop brought together nearly 200 scientists to discuss whether current scientific evidence on low dose effects and non-monotonic dose response curves for endocrine-active substances is sufficient to re-examine the ways in which chemicals are tested and assessed for human health effects. 

The meeting began with representatives from the academic community laying out the principles of endocrinology and evidence for the existence of non-monotonic dose responses and effects at low doses. These presentations were followed by experts from the risk assessment community detailing current risk assessment approaches and the possible implications for risk assessment and approaches to toxicity testing, if effects could be expected at environmentally relevant human exposure levels from substances acting via disruption of the endocrine system. There were then two separate breakout groups to discuss various aspects of the topics.

Drawing conclusions

According to Heindel, while there was not a consensus, many of the workshop participants were in agreement that non-monotonic dose responses do occur and these effects may be expected at some dose ranges for select chemicals. However, the extent to which adverse low dose responses might occur was considered to be a separate issue and was not as highly supported. Participants agreed that a more rigorous definition of low dose would be helpful as the term is not currently used consistently among toxicologists. There was also general agreement for a need to carry out a practical assessment of the type of effects that may be considered adverse in the context of endocrine disruption.

Some recommendations from the workshop include developing guidance on minimum data requirements for the publication of studies investigating endocrine disrupting activity so the data would be more useful for risk assessments, developing methods for data sharing, and creating a knowledge base for compiling findings of non-monotonic dose response relationships. There was also considerable discussion about ways that test guidelines might be augmented and evaluated with respect to detecting low-dose effects or non-monotonic dose responses.

The meeting was hosted in Berlin by Germany's Federal Environment Agency and the Charité Medical University of Berlin. Other sponsors of the workshop included the Danish Ministry of the Environment, Danish Technical University's National Food Institute, French Agency for Food, Environmental, and Occupational Health (ANSES), and the Oak Foundation.

(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.)

Maurice Whelan, Ph.D., Sharon Munn, Jerry Heindel, Ph.D., Gilbert Schoenfelder, M.D.

Workshop organizers took center stage in the lecture hall during a break in proceedings. Shown, left to right, are Maurice Whelan, Ph.D., and Munn, of JRC-IHCP; Heindel; and Gilbert Schoenfelder, M.D., of Charité Medical University of Berlin, Institute of Clinical Pharmacology and Toxicology. (Photo courtesy of European Commission)

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