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Measurement of Kinetic Parameters for Biotransformation of Polycyclic Aromatic Hydrocarbons by Trout Liver S9 Fractions: Implications for Bioaccumulation Assessment

Measurement of Kinetic Parameters for Biotransformation of Polycyclic Aromatic Hydrocarbons by... AbstractIntroduction: In vitro substrate depletion methods developed by the pharmaceutical industry are being used with increasing frequency to support chemical bioaccumulation assessments for fish. However, the application of these methods to high log Kow chemicals poses special challenges.Materials and Methods: Biotransformation of three polycyclic aromatic hydrocarbons (PAHs) was measured using trout liver S9 fractions. Studies were performed to evaluate the working lifetime of the S9 preparation, assess effects of chemical spiking solvents, and characterize the concentration-dependence of activity.Results: Derived kinetic constants (KM and Vmax) suggested that the three PAHs (phenanthrene, pyrene and benzo[a]pyrene) are transformed by the same reaction pathway and indicated an inverse correlation between KM and chemical log Kow. Reaction rates were proportional to unbound chemical concentrations except when these concentrations approached saturating levels, providing a direct demonstration of the free chemical hypothesis.Discussion: These findings suggest that previous in vitro work with high log Kow compounds has been conducted at inappropriately high substrate concentrations, resulting in underestimation of true in vivo activity. Preliminary calculations also indicate that PAH metabolism in fish may approach saturation during standardized in vivo testing efforts, potentially resulting in steady-state levels of accumulation greater than those that occur in a natural setting.Conclusion: The use of in vitro methods to predict metabolism impacts on chemical bioaccumulation in fish requires careful consideration of study conditions to ensure that measured rates of activity can be extrapolated with confidence to the intact animal. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Applied In Vitro Toxicology Mary Ann Liebert

Measurement of Kinetic Parameters for Biotransformation of Polycyclic Aromatic Hydrocarbons by Trout Liver S9 Fractions: Implications for Bioaccumulation Assessment

Measurement of Kinetic Parameters for Biotransformation of Polycyclic Aromatic Hydrocarbons by Trout Liver S9 Fractions: Implications for Bioaccumulation Assessment

Applied In Vitro Toxicology , Volume 4 (4): 14 – Dec 1, 2018

Abstract

AbstractIntroduction: In vitro substrate depletion methods developed by the pharmaceutical industry are being used with increasing frequency to support chemical bioaccumulation assessments for fish. However, the application of these methods to high log Kow chemicals poses special challenges.Materials and Methods: Biotransformation of three polycyclic aromatic hydrocarbons (PAHs) was measured using trout liver S9 fractions. Studies were performed to evaluate the working lifetime of the S9 preparation, assess effects of chemical spiking solvents, and characterize the concentration-dependence of activity.Results: Derived kinetic constants (KM and Vmax) suggested that the three PAHs (phenanthrene, pyrene and benzo[a]pyrene) are transformed by the same reaction pathway and indicated an inverse correlation between KM and chemical log Kow. Reaction rates were proportional to unbound chemical concentrations except when these concentrations approached saturating levels, providing a direct demonstration of the free chemical hypothesis.Discussion: These findings suggest that previous in vitro work with high log Kow compounds has been conducted at inappropriately high substrate concentrations, resulting in underestimation of true in vivo activity. Preliminary calculations also indicate that PAH metabolism in fish may approach saturation during standardized in vivo testing efforts, potentially resulting in steady-state levels of accumulation greater than those that occur in a natural setting.Conclusion: The use of in vitro methods to predict metabolism impacts on chemical bioaccumulation in fish requires careful consideration of study conditions to ensure that measured rates of activity can be extrapolated with confidence to the intact animal.

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Publisher
Mary Ann Liebert
Copyright
Copyright 2017, Mary Ann Liebert, Inc., publishers
ISSN
2332-1512
eISSN
2332-1539
DOI
10.1089/aivt.2017.0005
Publisher site
See Article on Publisher Site

Abstract

AbstractIntroduction: In vitro substrate depletion methods developed by the pharmaceutical industry are being used with increasing frequency to support chemical bioaccumulation assessments for fish. However, the application of these methods to high log Kow chemicals poses special challenges.Materials and Methods: Biotransformation of three polycyclic aromatic hydrocarbons (PAHs) was measured using trout liver S9 fractions. Studies were performed to evaluate the working lifetime of the S9 preparation, assess effects of chemical spiking solvents, and characterize the concentration-dependence of activity.Results: Derived kinetic constants (KM and Vmax) suggested that the three PAHs (phenanthrene, pyrene and benzo[a]pyrene) are transformed by the same reaction pathway and indicated an inverse correlation between KM and chemical log Kow. Reaction rates were proportional to unbound chemical concentrations except when these concentrations approached saturating levels, providing a direct demonstration of the free chemical hypothesis.Discussion: These findings suggest that previous in vitro work with high log Kow compounds has been conducted at inappropriately high substrate concentrations, resulting in underestimation of true in vivo activity. Preliminary calculations also indicate that PAH metabolism in fish may approach saturation during standardized in vivo testing efforts, potentially resulting in steady-state levels of accumulation greater than those that occur in a natural setting.Conclusion: The use of in vitro methods to predict metabolism impacts on chemical bioaccumulation in fish requires careful consideration of study conditions to ensure that measured rates of activity can be extrapolated with confidence to the intact animal.

Journal

Applied In Vitro ToxicologyMary Ann Liebert

Published: Dec 1, 2018

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