Assessment of Biotransformation Rates, Biomagnification, and Bioconcentration Factors of Difficult-to-Test Substances...

Area of Science:

• Environmental Chemistry
• Toxicology
• Ecotoxicology

Background:

• In vitro hepatic biotransformation assays offer a promising alternative to reduce animal testing and expedite bioaccumulation assessments for challenging substances.
• However, robust evidence demonstrating the accuracy and limitations of these in vitro methods for estimating in vivo biotransformation rates and bioaccumulation factors in fish is lacking.

Purpose of the Study:

• To present the first measurements of in vitro biotransformation rates for superhydrophobic and volatile siloxanes in rainbow trout liver S9 fractions.
• To extrapolate in vitro rates to predict in vivo biotransformation rates, bioconcentration factors (BCFs), and biomagnification factors (BMFs) in rainbow trout.
• To evaluate the agreement between in vitro and in vivo data and analyze the performance of in vitro to in vivo extrapolation (IVIVE) methods.

Main Methods:

• Measurement of in vitro biotransformation rates of siloxanes using rainbow trout liver S9 subcellular fractions.
• Extrapolation of in vitro biotransformation rates to estimate in vivo whole-body rates, BCFs, and BMFs.
• Comparison of in vitro-derived metrics with experimentally measured in vivo biotransformation rates, BCFs, and BMFs in rainbow trout.

Main Results:

• The study provides the first in vitro biotransformation rate measurements for superhydrophobic and volatile siloxanes in rainbow trout.
• Demonstrated the degree of agreement between in vitro and in vivo derived biotransformation rates, BCFs, and BMFs.
• Highlighted the influence of dosing concentrations and the significance of non-hepatic biotransformation on bioaccumulation metrics.

Conclusions:

• In vitro hepatic biotransformation assays show potential for estimating bioaccumulation of difficult-to-test substances like siloxanes.
• The study contributes valuable data for validating IVIVE methods and advancing bioaccumulation assessment strategies.
• Findings support the UN Stockholm Convention's goals by providing tools to reduce risks from biomagnifying pollutants in traditional foods.