Reliability of In Vitro Methods Used to Measure Intrinsic Clearance of Hydrophobic Organic Chemicals by Rainbow Trout: Results of an International Ring Trial

Toxicological Sciences : an Official Journal of the Society of Toxicology
John W NicholsMichelle Embry

Abstract

In vitro assays are widely employed to obtain intrinsic clearance estimates used in toxicokinetic modeling efforts. However, the reliability of these methods is seldom reported. Here we describe the results of an international ring trial designed to evaluate two in vitro assays used to measure intrinsic clearance in rainbow trout. An important application of these assays is to predict the effect of biotransformation on chemical bioaccumulation. Six laboratories performed substrate depletion experiments with cyclohexyl salicylate, fenthion, 4-n-nonylphenol, deltamethrin, methoxychlor, and pyrene using cryopreserved hepatocytes and liver S9 fractions from trout. Variability within and among laboratories was characterized as the percent coefficient of variation (CV) in measured in vitro intrinsic clearance rates (CLIN VITRO, INT; ml/h/mg protein or 106 cells) for each chemical and test system. Mean intralaboratory CVs for each test chemical averaged 18.9% for hepatocytes and 14.1% for S9 fractions, whereas interlaboratory CVs (all chemicals and all tests) averaged 30.1% for hepatocytes and 22.4% for S9 fractions. When CLIN VITRO, INT values were extrapolated to in vivo intrinsic clearance estimates (CLIN VIVO, INT; l/d/kg fish), b...Continue Reading

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Citations

Jun 4, 2020·Journal of Applied Toxicology : JAT·John WeeksPatrick D Guiney
Feb 29, 2020·Journal of Pesticide Science·Toshiyuki Katagi
Mar 3, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Melanie FischerKristin Schirmer
Jul 17, 2018·Environmental Sciences Europe·Kristina RehbergerHelmut Segner
May 18, 2019·Environmental Toxicology and Chemistry·Maria Therese HultmanAdam Lillicrap
Jul 8, 2020·Environmental Science & Technology·Heike LaueAndreas Natsch
Dec 28, 2018·Environmental Science & Technology·Elisabeth D ChangNic R Bury
Jan 9, 2021·Chemical Research in Toxicology·Sophia Krause, Kai-Uwe Goss

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