On the meta-analysis of hormetic effects.

The evidence for hormetic responses with chemical effects at doses lower than the no-observed-adverse-effect-level (sub-NOAEL) is increasing, creating a need for meta-analyses of sub-NOAEL effects across studies. However, the distinct features of hormetic responses complicate the procedures of meta-analyses aiming to study sub-NOAEL, hormetic effects, and there is no standardized methodology to serve as a guideline. In this piece, a protocol is proposed, which covers the selection of more holistic keywords to be integrated into the literature search queries, the designation of control, and the identification of NOAEL (and thus sub-NOAEL dose responses). It also considers the selection of the response indicators and the incorporation of time and dose as sources of variation. This protocol can serve as a reference point for a harmonized and more robust methodology to meta-analyze sub-NOAEL effects of chemicals on living organisms.