On May 3, 2016 the European Food Safety Authority published an external scientific report entitled “Review of non-monotonic dose-responses of substances for human risk assessment.” The report was commissioned by EFSA and prepared by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), the Austrian Agency for Health and Food Safety (AGES), the Institute of Environmental Medicine, Karolinska Institute (KI), Sweden, and the National Institute for Public Health and the Environment (RIVM), the Netherlands. The authors evaluated evidence for the non-monotonic dose-response (NMDR) hypothesis by reviewing the peer-reviewed scientific literature from the past decade (2002 onwards) for substances (other than essential nutrients) in the area of food safety. In total, the authors identified 202 in vivo datasets (from 49 studies), 311 in vitro datasets (from 91 studies) and 9 epidemiological/human datasets (from 2 studies) containing evidence for potential NMDRs. If feasible, the datasets were analyzed and evaluated for possible evidence of NMDR by applying six checkpoints. These checkpoints addressed both random and non-random errors, and the plausibility of NMDRs was assessed based on the number of fulfilled checkpoints. 10 of the in vivo and in contrast none of the in vitro datasets fulfilled all six checkpoints. The datasets from epidemiological/human studies could not be analyzed due to data limitations. The 10 in vivo datasets with the most robust evidence for NMDR included studies on four different substances: Quercetin, resveratrol, alpha-benzene hexachloride, and methyl-mercury.


Beausoleil, C. et al (2016). “Review of non-monotonic dose-responses of substances for human risk assessment.EFSA supporting publication (pdf)