In a commentary article published online on May 15, 2015 in the peer-reviewed journal Environmental Health, Thomas Zoeller and Laura Vandenberg discuss a recent proposal by Lagarde et al. on integrating non-monotonic dose responses (NMDRs) in chemical risk assessments (FPF reported). Zoeller and Vandenberg, both scientists at University of Massachusetts Amherst, U.S. have reported in 2012 on the existence of dose responses which do not follow Paracelsus’ “the dose makes the poison”, a principle which is used in chemical risk assessment today (FPF reported). In their recent commentary article they critique three specific aspects of the decision tree developed by Fabien Lagarde of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and colleagues, and suggest how this approach can be made more robust from the perspective of basic science.
In particular, Zoeller and Vandenberg reject the use of the Klimisch scores, an approach to evaluating the quality of scientific studies. They write that the Klimisch approach “is an industry-developed method which typically gives the highest quality rankings to industry funded studies”; additionally, only traditional toxicological endpoints are addressed but not those biological effects which would be relevant for “most chronic diseases in human populations today”, like diabetes.
Furthermore, Zoeller and Vandenberg suggest using topical experts for chemical risk assessments. In their view, “to evaluate the quality of a study designed to inform us about the ability of a manufactured chemical to interfere with hormone action, experts in the hormone system and physiological events under study must be recruited to contribute”.
Finally, the authors object to biological plausibility being a requirement for using NMDR data in risk assessment. They explain that understanding underlying mechanisms of how chemicals interact on the molecular scale with biological systems is complex and can take decades of research to obtain. The absence of this specific information should not stand in the way of regulatory action, even more so as this information is also presently not required in risk assessments of chemicals that exhibit a monotonic dose response.
Zoeller, T. and Vandenberg, L. (2015). “Assessing dose–response relationships for endocrine disrupting chemicals (EDCs): a focus on non-monotonicity.” Environmental Health (published online May 15, 2015)