Toxicology for real-life risk simulation - Editorial preface to this special issue.

In regulated chemicals, safe exposure limits are set based on a) in vivo studies of single chemicals administered at high doses to experimental animals, b) identification of the no-observed-adverse-effectlevel (NOAEL) assuming by default monotonicity and considering only apical effects of adversity, and c) using non-validated uncertainty factors, common for all chemicals. Though this is a practical and globally used approach, the vast majority of human real-life exposure scenarios have two main key components: low doses and many chemicals. The systematic neglection of a) real-life exposure scenarios, b) early signs of adversity at molecular or cellular level, and c) the potential for nonmonotonicity (e.g. endocrine disruptors), and d) chemicals’ interactions in both toxicokinetic and toxicodynamic (Sarigiannis and Hansen, 2012), challenges the real value of the existing “safety limits” (Dekant and Colnot, 2013). Even newly developed approaches such as grouping of chemicals for cumulative risk assessment are not considering real-life exposure scenarios as they are based on regulatory toxicology studies. Acknowledging the need for a paradigm shift of the current approaches for risk assessment towards a Real-Life Risk Simulation (RLRS) approach, the present special issue is intended to collect key articles and pioneering studies in support of this new area of toxicology.