title: Variation in predicted internal concentrations in relation to PBPK model complexity for rainbow trout.
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.
authors: UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany; Institute for Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Str. 29, 09596 Freiberg, Germany.
authors: E S
authors: ES
authors: Salmina
authors: UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany; Institute for Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Str. 29, 09596 Freiberg, Germany.
authors: D
authors: D
authors: Wondrousch
authors: UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany.
authors: R
authors: R
authors: Kühne
authors: Department of Chemistry, South Ural State Medical University, Vorovskogo 64, 454048, Chelyabinsk, Russia.
authors: V A
authors: VA
authors: Potemkin
authors: UFZ Department of Ecological Chemistry, Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany; Institute for Organic Chemistry, Technical University Bergakademie Freiberg, Leipziger Str. 29, 09596 Freiberg, Germany.
authors: G
authors: G
authors: Schüürmann
mesh_terms: D000818:Animals; D001711:Biotransformation; D004784:Environmental Monitoring; D007700:Kinetics; D008954:Models, Biological; D017686:Oncorhynchus mykiss / Q000502:physiology*; D014874:Water Pollutants, Chemical / Q000378:metabolism*
chemical_list: D014874:Water Pollutants, Chemical
keywords: Fish toxicity; Internal concentration; PBPK; Rainbow trout; Tissue partitioning