P04-07 Physiologically based toxicokinetic modelling of bisphenols in zebrafish (Danio rerio) accounting for variation in metabolic rates, brain distribution and liver accumulation

The present study is motivated by the increasing demand to consider internal partitioning into tissues instead of exposure concentrations for environmental toxicity assessment. To this end, physiologically based pharmacokinetic (PBPK) models can be applied. We evaluated variation in accuracy PBPK model outcomes depending on tissue constituents modeled as sorptive phases and chemical distribution tendencies addressed molecular descriptors. performance was examined using data from 150 experiments 28 chemicals collected US EPA databases. simplest “Kow-lipid content” approach being traditional toxicology. most elaborated one considers five biological (polar non-polar lipids, water, albumin remaining proteins) makes use LSER (linear solvation energy relationship) parameters describe compound behavior. content”-based shows more than order magnitude difference predicted measured values 37% studied while happens only 7%. It shown that further improvements could achieved introducing corrections metabolic biotransformation transmission hindrance through a cellular membrane. analysis interface polar constituents, namely lipids proteins, play an important role accumulation behavior compounds with H-bond donating functional groups. For without fragments preferable are storage water polarity.