Base-line model for identifying the bioaccumulation potential of chemicals

Abstract

The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF ) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important mitigating factor was found to be metabolism. Accordingly, a simulator for fish liver was used in the model, which has been trained to reproduce fish metabolism based on related mammalian metabolic pathways. Other significant mitigating factors, depending on the chemical structure, e.g. molecular size and ionization were also taken into account in the model. The results (r ² = 0.84) obtained for a training set of 511 chemicals demonstrate the usefulness of the BCF base line concept. The predictability of the model was evaluated on the basis of 176 chemicals not used in the model building. The correctness of predictions (abs(log BSF  ^Obs − log BCF  ^Calc) ≤ 0.75)) for 59 chemicals included within the model applicability domain was 80%.

Keywords:

• Bioconcentration factor
• Fish
• Metabolism
• QSAR model

Acknowledgements

This work was partially supported in part by ExxonMobil Biomedical Sciences, Inc. We greatly appreciate the bioaccumulation data for external validation provided by NITE Japan and the International project under 6FW program ALARM GOCE-CT-2003 – 50667.