Identifying environmental damage due to anthropogenic activities is a focal point for scientists and policy makers like those involved in the European Water Framework Directive (WFD). Many of these approaches focus on ecological endpoints for assessing environmental perturbations, which lead to policies emphasizing mitigation rather than prevention. Biomarkers provide early-warning indicators of stress but it is necessary to distinguish their natural variations from those induced by chemical stress. The global aim of this study was to establish a baseline assessment criterion (BAC) using historical data in a reference site to define toxicity thresholds. We have developed a multiple polynomial regression model (MPR) accounting the influence of salinity, temperature and size of individual on energetic reserves (glycogen and lipids) in the marine polychaete Hediste diversicolor. The model identified a complex, orthogonal relationship between confounding factors and glycogen and a linear relationship between lipids and size of individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.