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Toward improved models for predicting bioconcentration of well‐metabolized compounds by rainbow trout using measured rates of in vitro intrinsic clearance
Author(s) -
Nichols John W.,
Huggett Duane B.,
Arnot Jon A.,
Fitzsimmons Patrick N.,
CowanEllsberry Christina E.
Publication year - 2013
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.2219
Subject(s) - bioconcentration , rainbow trout , bioaccumulation , biotransformation , toxicokinetics , in vitro , environmental chemistry , chemistry , trout , fish <actinopterygii> , in vitro toxicology , toxicity , biology , biochemistry , fishery , enzyme , organic chemistry
Models were developed to predict the bioconcentration of well‐metabolized chemicals by rainbow trout. The models employ intrinsic clearance data from in vitro studies with liver S9 fractions or isolated hepatocytes to estimate a liver clearance rate, which is extrapolated to a whole‐body biotransformation rate constant ( k MET ). Estimated k MET values are then used as inputs to a mass‐balance bioconcentration prediction model. An updated algorithm based on measured binding values in trout is used to predict unbound chemical fractions in blood, while other model parameters are designed to be representative of small fish typically used in whole‐animal bioconcentration testing efforts. Overall model behavior was shown to be strongly dependent on the relative hydrophobicity of the test compound and assumed rate of in vitro activity. The results of a restricted sensitivity analysis highlight critical research needs and provide guidance on the use of in vitro biotransformation data in a tiered approach to bioaccumulation assessment. Environ Toxicol Chem 2013;32:1611–1622. © 2013 SETAC

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