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Title (Primary) Variation in predicted internal concentrations in relation to PBPK model complexity for rainbow trout
Author Salmina, E.S.; Wondrousch, D.; Kühne, R.; Potemkin, V.A.; Schüürmann, G.;
Journal Science of the Total Environment
Year 2016
Department OEC;
Volume 550
Language englisch;
POF III (all) T41;
Keywords Fish toxicity; PBPK; Internal concentration; Tissue partitioning; Rainbow trout
UFZ wide themes RU3;
Abstract The present study is motivated by the increasing demand to consider internal partitioning into tissues instead of exposure concentrations for the environmental toxicity assessment. To this end, physiologically based pharmacokinetic (PBPK) models can be applied. We evaluated the variation in accuracy of PBPK model outcomes depending on tissue constituents modeled as sorptive phases and chemical distribution tendencies addressed by molecular descriptors. The model performance was examined using data from 150 experiments for 28 chemicals collected from US EPA databases. The simplest PBPK model is based on the “Kow-lipid content” approach as being traditional for environmental toxicology. The most elaborated one considers five biological sorptive phases (polar and non-polar lipids, water, albumin and the remaining proteins) and makes use of LSER (linear solvation energy relationship) parameters to describe the compound partitioning behavior. The “Kow-lipid content”-based PBPK model shows more than one order of magnitude difference in predicted and measured values for 37% of the studied exposure experiments while for the most elaborated model this happens only for 7%. It is shown that further improvements could be achieved by introducing corrections for metabolic biotransformation and compound transmission hindrance through a cellular membrane. The analysis of the interface distribution tendencies shows that polar tissue constituents, namely water, polar lipids and proteins, play an important role in the accumulation behavior of polar compounds with H-bond donating functional groups. For compounds without H-bond donating fragments preferable accumulation phases are storage lipids and water depending on compound polarity.
ID 17089
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=17089
Salmina, E.S., Wondrousch, D., Kühne, R., Potemkin, V.A., Schüürmann, G. (2016):
Variation in predicted internal concentrations in relation to PBPK model complexity for rainbow trout
Sci. Total Environ. 550 , 586 - 597