Protein binding parameters to extrapolate from the in-vitro liver S9 metabolic assay to in-vivo rainbow trout (Oncorhynchus mykiss) bioaccumulation potential of hydrophobic organic chemicals

Escher, Beate I., Embry, Michelle R., Erhardt, Susan, Dyer, Scott, Kwon, Jung-Hwan, Halder, Marlies, Johanning, Karla, Nicols, John, Oosterwijk, Mattheus T. T., Rutishauser, Sibylle, Sahi, Jasminder and Segner, Helmut (2010). Protein binding parameters to extrapolate from the in-vitro liver S9 metabolic assay to in-vivo rainbow trout (Oncorhynchus mykiss) bioaccumulation potential of hydrophobic organic chemicals. In: SETAC Europe 20th Annual Meeting, Seville, Spain, (). 23-27 May 2010.

Author Escher, Beate I.
Embry, Michelle R.
Erhardt, Susan
Dyer, Scott
Kwon, Jung-Hwan
Halder, Marlies
Johanning, Karla
Nicols, John
Oosterwijk, Mattheus T. T.
Rutishauser, Sibylle
Sahi, Jasminder
Segner, Helmut
Title of paper Protein binding parameters to extrapolate from the in-vitro liver S9 metabolic assay to in-vivo rainbow trout (Oncorhynchus mykiss) bioaccumulation potential of hydrophobic organic chemicals
Formatted title
Protein binding parameters to extrapolate from the in-vitro liver S9 metabolic assay to in-vivo rainbow trout (Oncorhynchus mykiss) bioaccumulation potential of hydrophobic organic chemicals
Conference name SETAC Europe 20th Annual Meeting
Conference location Seville, Spain
Conference dates 23-27 May 2010
Publication Year 2010
Year available 2010
Sub-type Oral presentation
Language eng
Formatted Abstract/Summary
In vitro metabolic measurements using fish liver S9 fractions have the potential to provide rapid and cost-effective measurements of biotransformation potential by measuring intrinsic clearance rate of the parent chemical. A multi-sector team is undertaking a prevalidation study of the in vitro rainbow trout (Oncorhynchus mykiss) liver S9 metabolic assay to assess bioaccumulation potential of chemicals. However, a prerequisite for the application of in vitro assays is a prediction model that quantitatively links in vitro information to in vivo measures of bioconcentration. The first step in the extrapolation process is the estimation of liver in vivo intrinsic clearance by incorporating scaling factors relating the experimental test conditions from S9 metabolic stability evaluations to the whole liver. As a second step, this intrinsic clearance in the liver is combined with information on liver blood flow and the scaling factor fu. The term fu is the ratio of the free fraction of chemical in the blood to the free fraction of the chemical in the in vitro test system. There is currently no empirical equation for estimating the free fraction in S9 in in vitro tests. Therefore, we measured S9 and blood binding for the test chemicals used in the S9 metabolism study. Since they are very hydrophobic with log Kow between 4.5 and 6, classical dialysis methods are unsuitable. We therefore developed a three-phase partitioning method using silicone as third phase to determine the binding constants. The resulting values for S9 were very similar to bovine serum albumin binding constants and binding to blood plasma was two to ten times higher than binding to S9, presumably reflecting the higher lipid content in blood as compared to S9.
Subjects 030104 Immunological and Bioassay Methods
Keyword Bioconcentration
Extrapolation model
Metabolism
Protein binding
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: National Research Centre for Environmental Toxicology Publications
 
Versions
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Tue, 15 Feb 2011, 14:46:29 EST by Manjit Sanghera on behalf of National Res Centre For Environmental Toxicology