Saunders et al_IVIVE paper_Science Hub_entry_08142020

The purpose of is this study was to evaluate the potential for biotransformation in the gastrointestinal tissues (GIT) of fish to impact chemical bioaccumulation. In vitro biotransformation of two polycyclic aromatic hydrocarbons, pyrene (PYR) and benzo[a]pyrene (BAP), and two organic sunscreen agents, 2-ethylhexyl-4-methoxycinnamate (EHMC) and octocrylene (OCT), was measured using S9 fractions isolated from liver tissue and tissues of the upper GIT in rainbow trout. For PYR, BAP, and EHMC, activity was substantially higher in liver S9 fractions than in GIT S9 fractions. For OCT, activity was highest in GIT S9 fractions. An existing in vitro-in vivo extrapolation (IVIVE) model for fish, which yields a whole-animal biotransformation rate constant (kMET), was expanded to consider biotransformation in the GIT. The kMET values obtained using measured rates of in vitro activity (liver and GIT) were in good agreement with kMET values measured in controlled in vivo experiments, providing strong support for the IVIVE approach. Moreover, inclusion of GIT activity into the model prediction for OCT resulted in much better agreement with the empirical kMET estimate than was obtained using a ‘liver only’ model. These findings suggest that current ‘liver only’ approaches to IVIVE modeling may underestimate in vivo whole-animal biotransformation rates for chemicals that undergo substantial biotransformation in the GIT. Thus, failure to consider biotransformation in the GIT may lead to overestimation of true levels of bioaccumulation.

This dataset is associated with the following publication: Saunders, L., P. Fitzsimmons, J. Nichols, and F. Gobas. In vitro-in vivo extrapolation of hepatic and gastrointestinal biotrasnformation rates of hydrophobic chemicals in rainbow trout. AQUATIC TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 228: 1-12, (2020).