At the 2014 annual meeting of the European Societies of Toxicology (EUROTOX) and the Society of Toxicology (SOT) debaters discussed whether non-monotonic dose responses (NMDRs) at low-dose levels are toxicologically relevant.

During the EUROTOX 2014 meeting in Edinburgh, UK, Dieter Schrenk from the Technical University of Kaiserslautern, Germany, argued in favor of NMDRs and low dose effects. He was opposed by James Lamb (Exponent, U.S.).

Schrenk argued that many examples exist for endocrine disrupting chemicals (EDCs) exhibiting NMDRs and that low dose adverse effects below the traditional no observed adverse effect levels (NOAELs) have been reported and are plausible. He stressed that methodological shortcomings and lack of reproducibility have delayed the acceptance of low dose effects and that a refinement of the definition is needed. In future, open-minded research is necessary using adapted strategies in order to identify cases where low dose NMDRs may occur, Schrenk concluded.

In the counterposition, Lamb emphasized that it is critical to assess adversity of effects. He noted that the majority of examples for NMDRs, as collected by Vandenberg et al. (2012) for over 70 EDCs, are in fact not relevant. Lamb highlighted that better data for more substances are needed regardless of whether or not they are EDCs. Lamb encouraged development of new methods and the use of a range of testing doses. Overall, he concluded that there were more pertinent topics for toxicological research than NMDRs and low dose effects.

The vote taken after the debate could not conclusively establish a majority for either position.

Read more

Toxicology Letters, 229, S3. “EUROTOX/SOT Debate – Are non-monotonic dose-responses at low dose levels toxicologically relevant?