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).

Organic ultraviolet filters (UVFs; also known as sunscreen agents) used in personal care and consumer products can enter the aquatic environment via wastewater treatment plant effluents or by loss from skin during swimming and other recreational activities. Some UVFs are hydrophobic (log Kow > 4) which has led to concern that they may bioaccumulate in aquatic organisms. The purpose of this study was to investigate the bioaccumulation and biotransformation of two widely-used UVFs, 2-ethylhexyl-4-methoxycinnamate (EHMC) and octocrylene (OCT) in rainbow trout exposed via the diet. EHMC and OCT were significantly metabolized by trout and this metabolism substantially reduced bioaccumulation relative to levels observed for a set of poorly transformed chemicals having similar log Kow values. Derived bioconcentration factors (BCFs) and biomagnification factors (BMFs) for both UVFs were well below established bioaccumulation criteria, suggesting that EHMC and OCT are unlikely to pose a bioaccumulation hazard in trout. This research substantially increases existing knowledge concerning the fate and effects of UVFs in the environment. This dataset is associated with the following publication: Saunders, L., A. Hoffman, J. Nichols, and F. Gobas. Dietary bioaccumulation and biotransformation of hydrophobic organic sunscreen agents in rainbow trout. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 39(3): 574-586, (2020).

The dataset, which is presented as an Excel spreadsheet, contains all data which is presented as figures in Nichols et al., Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment, accepted for publication in Applied In Vitro Toxicology 04/2017. Additional information if provided regarding reaction conditions used to characterize liver S9 fractions and perform PAH depletions studies. This dataset is associated with the following publication: Nichols, J., M. Ladd, and P. Fitzsimmons. Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 4(4): 365-378, (2018).

The dataset, which is presented as an Excel spreadsheet, contains all data which is presented as figures in Nichols et al., Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment, accepted for publication in Applied In Vitro Toxicology 04/2017. Additional information if provided regarding reaction conditions used to characterize liver S9 fractions and perform PAH depletions studies. This dataset is associated with the following publication: Nichols, J., M. Ladd, and P. Fitzsimmons. Measurement of kinetic parameters for biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Implications for bioaccumulation assessment. Applied In Vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 4(4): 365-378, (2018).

This paper described development of an in vitro/in vivo model that accounts for first pass clearance effects. The model details are contained in the supporting information for the paper. This dataset is associated with the following publication: Saunders, L., J. Nichols, J.A. Arnot, J. Armitage, and F. Wania. An amended in vitro–in vivo extrapolation model that accounts for first pass clearance effects on chemical bioaccumulation in fish. Environmental Science: Processes & Impacts. Royal Society of Chemistry, Cambridge, UK, 25(4): 741-754, (2023).

This ScienceHub entry was developed for the published paper: Consoer et al., 2016, Toxicokinetics of perfluorooctane sulfonate in rainow trout (Oncorhynchus mykiss), Environ. Toxicol. Chem. 35:717-727. Individual rainbow trout were exposed to PFOS by bolus injection (elimination studies) or by adding PFOS to incoming water (branchial uptake studies). The trout were fitted with indwelling catheters and urinary cannulae to permit periodic collection of blood and urine. Additional sampling was conducted to evaluate PFOS uptake from and elimination to respired water. Data obtained from each fish was evaluated using a clearance-volume pharmacokinetic model. Modeled kinetic parameters were then averaged to develop summary statistics which were used as a basis for interpreting modeled results and making comparisons to a previous study of rainbow trout exposed to perfluorooctanoate (PFOA; Consoer et al., 2014, Aquat. Toxicol. 156:65-73). The results of this study, combined with that of the previous PFOA study, suggest that PFOA is a substrate for renal transporters in fish while glomerular filtration alone may be sufficient to explain the observed renal elimination of PFOS. These findings demonstrate that models developed to predict the bioaccumulation of perfluoroalkyl acids by fish must account for differences in renal clearance of individual compounds. This dataset is associated with the following publication: Consoer, D., A. Hoffman , P. Fitzsimmons , P. Kosian , and J. Nichols. Toxicokinetics of perfluorooctane sulfonate in rainbow trout (Oncorhynchus mykiss). ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 35(3): 717-727, (2016).

This dataset, presented as an Excel spreadsheet, contains all data presented as figures and tables in an article by Nichols et al, entitled "In vitro-in vivo extrapolation of hepatic biotransformation data for fish. III. An in-depth case study with pyrene" and published in Environmental Toxicology and Chemistry, 2023. The dataset describes results from a paired set of experiments designed to evaluate the accuracy of in vitro to in vivo metabolism extrapolation procedures for fish. Results showed that measured rates of in vitro intrinsic clearance, when extrapolated to the whole liver, underestimated apparent rates of in vivo activity by about a factor of 4 (assuming the liver is the only site of biotransformation). These findings may have important implications for the use of IVIVE methods in bioaccumulation assessments for fish. This dataset is associated with the following publication: Nichols, J., P. Fitzsimmons, A. Hoffman, and K. Wong. In vitro-in vivo extrapolation of hepatic biotransformation data for fish. III. An in-depth case study with pyrene. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(7): 1501-1515, (2023).

This dataset describes the results of a set of experiments, the goal of which was to evaluate the effects of protease inhibitors on the trout liver S9 substrate depletion assay. The presented data show that addition of phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, substantially increases the working lifetime of the trout S9 assay, resulting in improved detection of low intrinsic clearance rates. These findings substantially increase the utility of the trout S9 assay and may have broad implications for its use to support chemical bioaccumulation assessments. This dataset is associated with the following publication: Nichols, J., A. Hoffman, J. Swintek, S. Droge, and P. Fitzsimmons. Addition of phenylmethylsulfonyl fluoride (PMSF) substantially increases the working lifetime of the trout liver S9 substrate depletion assay resulting in improved detection of low intrinsic clearance rates. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 40(1): 148-161, (2021).

This dataset describes the results of a set of experiments, the goal of which was to evaluate the effects of protease inhibitors on the trout liver S9 substrate depletion assay. The presented data show that addition of phenylmethylsulfonyl fluoride (PMSF), a serine protease inhibitor, substantially increases the working lifetime of the trout S9 assay, resulting in improved detection of low intrinsic clearance rates. These findings substantially increase the utility of the trout S9 assay and may have broad implications for its use to support chemical bioaccumulation assessments. This dataset is associated with the following publication: Nichols, J., A. Hoffman, J. Swintek, S. Droge, and P. Fitzsimmons. Addition of phenylmethylsulfonyl fluoride (PMSF) substantially increases the working lifetime of the trout liver S9 substrate depletion assay resulting in improved detection of low intrinsic clearance rates. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 40(1): 148-161, (2021).

This Excel spreadsheet provides data that appear in Tables 1- 2 and Figures 1-4 of the main document, as well as data that appear in Figures S1-S3 of the Supplementary Information. This dataset is associated with the following publication: Nichols, J., M. Ladd, A. Hoffman, and P. Fitzsimmons. Biotransformation of polycyclic aromatic hydrocarbons by trout liver S9 fractions: Evaluation of competitive inhibition using a substrate depletion approach. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 38(12): 2729-2739, (2019).