EFSA requested its Scientific Committee to prepare a guidance document providing generic issues and criteria to consider biological relevance, particularly when deciding on whether an observed effect is of biological relevance, i.e. is adverse (or shows a positive health effect) or not.
The opinion clarifies a number of definitions and concepts, such as, responses of a biological system to exposure, mode of action and adverse outcome pathways, thresholds, critical effect, modelling approaches, biomarkers, which are central to biological relevance and in order to achieve that these concepts are used in a consistent way across EFSA areas of activity.
The list of generic issues (e.g. nature and size of the biological changes or differences, including the relevance of the biological systems were the effects are observed) to consider when deciding on whether an observed effect is biologically relevant should be applicable to all relevant EFSA Scientific Panels and Scientific Committee.
A framework was developed in which biological relevance is considered at three main stages related to the process of dealing with evidence: 1) Development of the assessment strategy, in this context, specification of agents, effects, subjects and conditions. 2) Collection and extraction of data, i.e. identification of potentially biologically relevant evidence/data as specified in the Assessment strategy. 3) Appraisal of the relevance of the agents, subjects, effects and conditions, i.e. reviewing dimensions of biological relevance for each data set: a) Agent; it should be considered whether the assessment is based on the agent of concern or on a surrogate agent. b) Subject; in case proxies are used consider the relevance of effects occurring in these for the subject under assessment. c) Effect; a wide variety of effects may be considered. Consideration should be given as to whether the effect is causally related to exposure to the agent, and the nature of the effect should also be taken into account, i.a. homeostatic response, adaptive, directly or indirectly adverse or beneficial. Finally for effects where the size of the effect is critical, it should be assessed whether the magnitude of the effect is sufficient to be of biological relevance and thereby of importance for the assessment outcome. It should be noted that the biological relevance of an effect could vary according to the assessment question. d) Conditions; it should be considered whether the conditions of a biological (test) system, e.g. exposures, models, are relevant for the assessment.