A ready-to-use online tool to calculate the BCF of active substances: MOSAIC bioacc

Abstract

Toxicokinetic/toxicodynamic (TKTD) models are used to describe and predict the toxicity and the effects of chemical substances on individual traits based on experimental data. The toxicokinetic (TK) part describes the relationship between the exposure medium and the organism, considering various processes such as ADME (accumulation, depuration, metabolization and excretion). Regulation laying down the data requirements for active substances for the placing of plant protection products on the market, a bioaccumulation study on fish is required for substances with a partition coefficient octanol / water greater than or equal to 3, following the OECD guideline 305. Such a TK test allows to define the bioconcentration factor (BCF), the biomagnification factor (BMF) or the bioaccumulation factor (BAF). These factors are decisive criteria for estimating the concentration of active substances present in food items of vertebrates and more particularly of piscivorous birds and mammals. In a recent study, a relevant inference framework (Bayesian inference) was proposed to estimate toxicokinetic model parameters accounting for their correlation, based on the experimental data from standard guidelines and leading to the calculation of BCF/BMF/BAF. Models underlying this framework can be directly integrated and used as TK parts of TKTD models. Achieved in agreement with EFSA's scientific opinion on good modeling practices, the objective of this project is to develop a ready-to-use on-line tool for easily estimating BCF/BMF/BAF in a regulatory framework, by taking into account bioaccumulation of a parent compound and its metabolites through biotransformation. We built a Shiny interface to make available the inference method and the BCF/BMF/BAF calculation from the MOSAIC platform, which may be used for research as well as by companies or regulatory agencies. This tool will be integrated more broadly into the development and widespread use of TKTD models within the risk assessment framework.