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Quantitative in vitro - in vivo extrapolation of biotransformation rates for bioaccumulation assessment: Focus on organic sunscreen agents in trout
Citation:
Saunders, L., A. Hoffman, P. Fitzsimmons, J. Nichols, AND F. Gobas. Quantitative in vitro - in vivo extrapolation of biotransformation rates for bioaccumulation assessment: Focus on organic sunscreen agents in trout. SETAC North America, Sacramento, CA, November 04 - 08, 2018.
Impact/Purpose:
In vitro-in vivo extrapolation (IVIVE) methods used to incorporate measured rates of in vitro biotransformation into predictive bioaccumulation models have been developed and evaluated using a relatively small number of chemicals. Moreover, efforts to validate these methods by comparing predicted (by IVIVE) and measured (in vivo) rates of biotransformation have been restricted by the lack of paired data for fish of the same species, size, and life stage. In this study, trout were exposed to two hydrophobic organic sunscreen agents, ethylhexyl methoxycinnamate (EHMC) and octocrylene (OCT), to measure in vivo biotransformation. The same animals were then sampled to measure in vitro biotransformation using S9 fractions from liver and gut tissues. The agreement between measured in vivo biotransformation rates (whole-body basis) and those predicted by IVIVE using data from liver S9 fractions was generally good. For OCT, however, this agreement was substantially improved by incorporating data from gut S9 fractions. These findings suggest that current IVIVE methods provide good predictions of in vivo metabolism. For some compounds, however, there is substantial metabolism within tissues of the GIT. Failure to properly account for this activity could result in overestimation of true bioaccumulation potential.
Description:
Recent studies demonstrate the utility of in vitro-in vivo extrapolation (IVIVE) approaches for estimating the impact of hepatic biotransformation on chemical bioaccumulation in fish. Invitrobiotransformation measurements are reliable and reproducible1which has led to the recent adoption of the OECD test guidelines 319 A & B. Results to date show that bioconcentration factors (BCF) calculated by incorporating measured in vitrobiotransformation rates into established BCF models are closer to measured values than BCFs generated under the assumption of no metabolism2. Nevertheless, there is a consistent tendency for IVIVE methods to overestimate BCFs relative to empirical BCFs. These apparent underestimates of in vivo biotransformation rates may be due to: •Current IVIVE procedures ignore the possible contribution of extra-hepatic biotransformation •Errors with respect to the specification of the hepatic clearance binding correction term (fU) •Few empirical in vivo biotransformation rates to directly test extrapolated in vitro estimates Here we present results from both in vitroand in vivoexperiments that measured biotransformation rates of two organic sunscreen agents (ultraviolet filters; UVFs), ethylhexylmethoxycinnamate(EHMC) and octocrylene (OCT) in rainbow trout