AUTHOR=Bischof Ina , Arnot Jon A. , Jürling Heinrich , Knipschild Georg , Schlechtriem Christian , Schauerte Anna , Segner Helmut 

TITLE=In vitro biotransformation assays using fish liver cells: Comparing rainbow trout and carp hepatocytes

JOURNAL=Frontiers in Toxicology

VOLUME=4

YEAR=2022

URL=https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2022.1021880

DOI=10.3389/ftox.2022.1021880

ISSN=2673-3080

ABSTRACT=<p>Biotransformation assays using primary hepatocytes from rainbow trout, <italic>Oncorhynchus mykiss</italic>, were validated as a reliable <italic>in vitro</italic> tool to predict <italic>in vivo</italic> bioconcentration factors (BCF) of chemicals in fish. Given the pronounced interspecies differences of chemical biotransformation, the present study aimed to compare biotransformation rate values and BCF predictions obtained with hepatocytes from the cold-water species, rainbow trout, to data obtained with hepatocytes of the warm-water species, common carp (<italic>Cyprinus carpio</italic>). In a first step, we adapted the protocol for the trout hepatocyte assay, including the cryopreservation method, to carp hepatocytes. The successful adaptation serves as proof of principle that the <italic>in vitro</italic> hepatocyte biotransformation assays can be technically transferred across fish species. In a second step, we compared the <italic>in vitro</italic> intrinsic clearance rates (CL<sub>in vitro, int</sub>) of two model xenobiotics, benzo[a]pyrene (BaP) and methoxychlor (MXC), in trout and carp hepatocytes. The <italic>in vitro</italic> data were used to predict <italic>in vivo</italic> biotransformation rate constants (k<sub>B</sub>) and BCFs, which were then compared to measured <italic>in vivo</italic> k<sub>B</sub> and BCF values. The CL<sub>in vitro, int</sub> values of BaP and MXC did not differ significantly between trout and carp hepatocytes, but the predicted BCF values were significantly higher in trout than in carp. In contrast, the measured <italic>in vivo</italic> BCF values did not differ significantly between the two species. A possible explanation of this discrepancy is that the existing <italic>in vitro-in vivo</italic> prediction models are parameterized only for trout but not for carp. Therefore, future research needs to develop species-specific extrapolation models.</p>