Regulatory assessment of aquatic bioaccumulation: a contribution from QSAR and chemometrics.

Bioaccumulation is the process by which the concentration of a chemical in an organism exceeds that measured in the surrounding environment. It occurs through non‐dietary routes (e.g., through skin or respiratory surfaces) for what is known as bioconcentration, and/or through predator‐prey transport from diet. In most of national and international regulations, the detection of bioaccumulative chemicals relies on the bioconcentration capability. However, in some cases, the actual bioaccumulation can be more than 1 order of magnitude greater than that expected from the bioconcentration, due to storage through diet. This work targeted the development of a QSAR model to predict the bioaccumulation through the diet (i.e., Biomagnification Factor [BMF]). To allow for a regulatory application, the model was chosen as the best compromise between complexity and prediction accuracy, in terms of modelling method and interpretability of the molecular descriptors. The final model is a consensus of an Ordinary Least Squares and a k‐Nearest Neighbour models, which was developed on 214 compounds and led to accurate estimates of logBMF (RMSEPext = 0.45 l.u. and Q2ext = 0.82). To the best of our knowledge, no QSAR models for BMF developed on heterogeneous chemical sets currently exist. In addition, the work shows how the model and descriptor interpretations can be leveraged into a greater understanding of the structural features responsible for the underlying biological mechanisms