Review of the Berlin Workshop Concerning Low Dose Effects and Non-monotonic Dose response for EACs (Endocrine Active Chemicals)

Sharyle Patton
Director of CHE Special Projects

Read more about this workshop held September 11 – 13, 2012.

The official workshop report will be published in a few weeks by workshop organizers, but I want to give you a sense right away of the nature and content of discussions.

First, the workshop successfully brought together experts and researchers in toxicology, endocrinology and epidemiology with European risk assessment regulators to discuss the implications of low dose effects and non-monotonic dose response curves for risk/safety assessment—or, endocrinology meets toxicology. If exposures to toxic chemicals at the low levels currently measured in the environment can cause harm through endocrine disruption, then risk assessment may need to change its approaches to toxicity testing.

Members from the chemical industry and the public interest community also participated in the workshop discussions, but the focus of discussion for all was the possibility of integration of the principles of endocrinology into current risk assessment practices and whether such integration requires a major overhaul of standard risk assessment or whether a few tweaks here and there might be sufficient.

The workshop was co-sponsored by the Joint Research Centre’s Institute for Health and Consumer Protection (European Commission) and the US National Institute for Environmental Health Sciences/NIH.

Workshop goals, as identified in workshop materials, included identifying “research needs required to move closer to scientific agreement on low dose effects and non-monotonic dose responses for endocrine active substances”, defining how “research programs could support studies, especially those funded by public agencies, that could produce data most useful for a science-based risk assessment, and developing “a plan to continue discussions between basic researchers and risk assessment scientists.”

The meeting began with opening statements by Jerry Heindel, NIEHS, and Sharon Munn, EC, followed by presentations from scientists such as Laura Vandenberg, Fred vom Sal, Tyrone Hayes, Heather Patisaol, Ana Soto and others who described the principles of endocrinology and evidence for the existence of non-monotonic dose responses and effects at low doses (i.e. doses in the range of estimated environmental human exposure).

European and US regulatory agency representatives from EPA, OECD, NTP, ANSES, EFSA and other agencies discussed their current programs for assessing chemicals for toxicity. We then moved to small breakout groups in which individuals were encouraged to step into concrete problem solving, responding to questions that had been circulated to all participants before arrival in Berlin.

In these workshops we took on such topics as the definition of “low dose” and whether there needs to be a standard definition, or whether a definition can be specified given the scope and intent of a particular study; we talked about the definition of endocrine disruption and of adverse effect and whether low dose reesponse is different and needs to be considered separately from non-monotonic dose curve response; we discussed ideas for improving test guidelines for low dose research; and, given the complexity and number of factors, including funding, that complicate low dose testing, we talked about “reproducibility,” a key criterion for assessing validity of scientific research, possibly being defined as general trends across a range of similar low dose studies.

Each breakout session then offered best ideas and suggested further questions for consideration by the entire group. Within the full group meetings, we each participated in electronic polling through our individual “clickers.” This polling provided everyone the opportunity to support or reject breakout group report-back recommendations projected on a screen in front of the assembly. There was no way to connect any given “click” to an individual, so everyone could anonymously step outside the safe harbor of agendas or official positions to click support (or not). The polling technology then projected outcomes of the polling, and we could see where consensus occurred or shifted, and where it did not, over the course of the meeting. This immediate feedback gave the meeting a sense of direction and energy…participants found it very useful.

Key to the smooth functioning of the meeting was RESOLVE, professional facilitators, and all non-scientists, who guided us through some tough conversations. There were a few brushfires, but very few, and the skill of these neutral and wise folks made the difference.

This meeting was an excellent next step, after PPTOX, towards incorporating low dose and non-monotonic dose response into risk assessment. The official meeting press release lists the following meeting recommendations as including:

  1. Developing guidance on minimum information requirements for publishing studies investigating endocrine disrupting activity,
  2. Finding mechanisms for sharing of raw data from experimental studies
  3. Creating a knowledge base for compiling findings of non-monotonic dose response relationships.

These are major new steps forward.

My own sense regarding other highlights include how well that the anonymous polling seemed to catalyze deeper discussion; how many of the young women, likely moms or considering motherhood and who are responsible for developing risk assessment policies, became enthusiastically engaged in learning more about endocrine distupting chemicals (EDCs), and how the workshop created a dynamic for moving forward at the highest levels around the major issues discussed at the workshop.

The meeting formal report will be published in the next few weeks, with subsequent commentary by workshop sponsors, so stay tuned.

NGOs in attendance included:

Meeting sponsors:

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