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Concentration dependence of in vivo biotransformation rates of organic sunscreen agents in rainbow trout following a dietary exposure
Citation:
Saunders, L., A. Hoffman, J. Nichols, AND F. Gobas. Concentration dependence of in vivo biotransformation rates of organic sunscreen agents in rainbow trout following a dietary exposure. SETAC North America, Orlando, FL, November 06 - 10, 2016.
Impact/Purpose:
not applicable
Description:
Simple diffusion lipid-partitioning models have historically described the bioaccumulation of hydrophobic chemicals in fish. While these models are sufficient to describe the bioaccumulation of recalcitrant PCBs and other non-metabolized chemicals, they are inadequate for chemicals that are biotransformed. Consequently, efforts have been made to improve bioaccumulation models by incorporating estimated chemical biotransformation rates. While bioaccumulation models have become more sophisticated, they continue to assume that chemical uptake and elimination are independent of chemical (exposure) concentration, although this assumption has been scarcely investigated. The concentration dependence of in vitro hepatic biotransformation rates has been recently illustrated and is an important consideration for in vitro to in vivo extrapolation (IVIVE) of biotransformation data. Assays performed at substrate concentrations exceeding the Michaelis Menten affinity constant (Km) may underestimate a chemical’s intrinsic clearance rate, potentially resulting in underestimates of in vivo hepatic clearance and overestimates of modeled bioaccumulation. These outcomes depend, however, on the relationship between tested in vitro concentrations and the in vivo concentration achieved the liver (C liv ). In this study, we investigated the relationship between dietary exposure concentration and observed accumulation and elimination of two organic ultraviolet filters (UVFs): ethylhexyl trimethoxycinnamate and octocrylene (log Kow of 5.8 and 6.9, respectively). Three dietary concentrations of UVFs covering 2 orders of magnitude were selected to result in a range of anticipated C liv values. Rainbow trout were exposed over a 14d uptake period and 14d depuration period. Fish were collected during the 28d exposure and tissues (plasma, liver, gastrointestinal tract, carcass) were extracted and analyzed for chemical concentration. Fish were simultaneously exposed to non-biotransformed reference chemicals. The decline in chemical concentration over the depuration period wascompared between the UVFs and reference chemicals to estimate k MET for the UVFs. The influence of varying dietary concentrations on k MET was then evaluated. Data generated from this test will be used to inform IVIVE approaches in bioaccumulation assessment.