IN VITRO TO IN VIVO EXTRAPOLATION OF BIOTRANSFORMATION RATES FOR ASSESSING BIOACCUMULATION OF HYDROPHOBIC ORGANIC CHEMICALS IN MAMMALS
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| Authors: | Lee, YS; Lo, JC; Otton, SV; Moore, MM; Kennedy, CJ; Gobas, FAPC |
| Year: | 2017 |
| Journal: | Environmental Toxicology and Chemistry 36: 1934-1946 Article Link (DOI) |
| Title: | IN VITRO TO IN VIVO EXTRAPOLATION OF BIOTRANSFORMATION RATES FOR ASSESSING BIOACCUMULATION OF HYDROPHOBIC ORGANIC CHEMICALS IN MAMMALS |
| Abstract: | Incorporating biotransformation in bioaccumulation assessments of hydrophobic chemicals in both aquatic and terrestrial organisms in a simple, rapid, and cost-effective manner is urgently needed to improve bioaccumulation assessments of potentially bioaccumulative substances. One approach to estimate whole-animal biotransformation rate constants is to combine in vitro measurements of hepatic biotransformation kinetics with in vitro to in vivo extrapolation (IVIVE) and bioaccumulation modeling. An established IVIVE modeling approach exists for pharmaceuticals (referred to in the present study as IVIVE-Ph) and has recently been adapted for chemical bioaccumulation assessments in fish. The present study proposes and tests an alternative IVIVE-B technique to support bioaccumulation assessment of hydrophobic chemicals with a log octanol-water partition coefficient (K-OW) >= 4 in mammals. The IVIVE-B approach requires fewer physiological and physiochemical parameters than the IVIVE-Ph approach and does not involve interconversions between clearance and rate constants in the extrapolation. Using in vitro depletion rates, the results show that the IVIVE-B and IVIVE-Ph models yield similar estimates of rat whole-organism biotransformation rate constants for hypothetical chemicals with log K-OW >= 4. The IVIVE-B approach generated in vivo biotransformation rate constants and biomagnification factors (BMFs) for benzo[a] pyrene that are within the range of empirical observations. The proposed IVIVE-B technique may be a useful tool for assessing BMFs of hydrophobic organic chemicals in mammals. (C) 2016 SETAC |
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