EFSA Scientific Colloquium N°17: Low dose response in toxicology and risk assessment

Scientists debate low-dose hypothesis at EFSA’s international colloquium

Over two days, 100 scientific experts exchanged views and debated the possible health effects of low levels of certain chemicals (the “low-dose hypothesis”) and the current and future challenges these pose for food and feed risk assessment.

The European Food Safety Authority (EFSA)’s 17th Scientific Colloquium attracted risk assessors, risk managers, scientists and stakeholders from 21 countries, including 12 EU Member States, 4 candidate countries, Japan, Norway, Russia, Switzerland and the United States.

Prominent toxicologists, endocrinologists and biochemists from academia, industry and public health authorities took part, including representatives of several European National Competent Authorities, the European Commission, the Joint Research Centre (JRC), the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR), the European Chemicals Agency (ECHA) and the U.S. Food and Drug Administration (FDA).

The Colloquium came at a potentially critical juncture in a scientific debate that has been gaining prominence since the 1990s: increasing numbers of studies address effects of chemical substances at low doses, mainly those substances referred to as endocrine active substances or endocrine disruptors. According to the low-dose hypothesis, these substances may cause adverse effects at low doses but not necessarily at all higher doses. They do not therefore follow the classical (or “monotonic”) dose-response curve, showing a greater likelihood of an adverse effect at higher doses. Rather they may show a different kind of dose-response curve, e.g. a U-shaped curve with responses both at low- and high-dose levels but not in intermediate ranges. Such a dose-response curve is termed a non-monotonic dose-response curve. Such findings challenge current concepts in chemical risk assessment.

As yet no scientific consensus has been reached as to the validity of the low-dose hypothesis. Recently, it has been claimed that a large number of new studies provide further support for this hypothesis. The relevance of these findings and the way they could impact on assessment of the possible risks of chemicals in food and feed were the main topic of this event.

Following an introductory session where speakers summarised the current debate, participants were divided into four discussion groups each focusing on a specific key issue: the nature of an effect and the assessment of adversity; dose response relationships; the evidence for non-monotonic dose response curves; the challenges for risk assessment. Related aspects were covered during the course of the debates, including effects of endocrine active substances, testing methods and strategies, and modelling techniques for predicting biological responses.

The objective of EFSA’s scientific colloquia is to bring together international experts from different sectors for an open scientific debate on key issues; they are organised so as to provide ample opportunity for the exchange of views.

The Head of EFSA’s Food Packaging and Ingredients Unit, Claudia Heppner, stated that “The participants at the Colloquium discussed in a constructive atmosphere the existing views and scientific evidence related to the low-dose hypothesis. This is important for considering whether or not EFSA needs to look at the low-dose hypothesis in more detail. It could have an important impact on EFSA’s work in several areas.”

According to Alexandre Feigenbaum, EFSA’s joint-Chair of the event: “There are still many uncertainties surrounding this debate but we have moved the discussion on this week. We have identified some key scientific questions and next steps in terms of methodology requirements, research gaps, appropriate testing strategies and methods, and the use of predictive tools. The debate will go on and needs to involve a range of scientific disciplines. EFSA will continue to motivate and evaluate those discussions and the possible impact for its risk assessment work.”

The outcome of the colloquium will be summarised in a report to be published in the autumn.