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).

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 purpose of this study was to compare two in vitro systems, cryopreserved trout hepatocytes and trout liver S9 fractions, used to predict in vivo levels of biotransformation in fish. This information is needed to refine modeled estimates of bioaccumulation for hydrophobic organic chemicals that undergo biotransformation. In this effort we used trout hepatocytes to measure in vitro biotransformation of 6 polycyclic aromatic hydrocarbons (PAHs). The results were compared to metabolism rates reported previously for trout liver S9 fractions. Results obtained using both in vitro systems were then used to predict measured levels of hepatic clearance for the same test chemicals exhibited by isolated perfused livers. The results of this study suggest that both in vitro systems are well suited for performing in vitro-in vivo metabolism extrapolations with fish as a means for improving modeled bioaccumulation predictions. This dataset is associated with the following publication: Fay, K., P. Fitzsimmons, A. Hoffman, and J. Nichols. Comparison of trout hepatocytes and liver S9 fractions as in vitro models for predicting hepatic clearance in fish. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, FL, USA, 36(2): 463-471, (2017).

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).

This dataset illustrates relationships between body weight and hepatic phase I and phase II metabolic activity in rainbow trout. This dataset is associated with the following publication: Fitzsimmons, P., A. Hoffman, K. Fay, and J. Nichols. Allometric scaling of hepatic biotransformation in rainbow trout.. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY PART C: TOXICOLOGY & PHARMACOLOGY. Elsevier Science Ltd, New York, NY, USA, 214: 52-60, (2018).

This dataset provides measured in vitro intrinsic clearance rates for 54 chemicals tested using isolated hepatocytes from humans, rats, and rainbow trout. The test chemicals were selected to provide broad coverage across the industrial and pesticidal chemical space while also prioritizing chemicals of interest to EPA’s Endocrine Disruptor Screening Program (EDSP). A data evaluation framework was developed to identify results suitable for rate reporting. Acceptable results were then used to evaluate the chemical domain of applicability of the applied methods, the influence of starting substrate concentration on measured rates of intrinsic clearance, and differences in metabolic activity among species. These findings provide data for chemicals of specific interest to the EDSP. More importantly, the results provide critical guidance on future use of in vitro biotransformation assays to support high-throughput chemical risks assessments. This dataset is associated with the following publication: Black, S., J. Nichols, K. Fay, S. Matten, and S. Lynn. Evaluation and comparison of in vitro intrinsic hepatic clearance rates measured using cryopreserved hepatocytes from humans, rats, and rainbow trout. TOXICOLOGY. Elsevier Science Ltd, New York, NY, USA, 457: 152819, (2021).

This repository contains the necessary data, python source code and jupyter notebooks to reproduce the results from our manuscript, "Estimating Hepatotoxic Doses Using High-content Imaging in Primary Hepatocytes." Using in vitro data to estimate point of departure (POD) values is an important component of new approach method (NAM)-based chemical risk assessments. In this case study we evaluated a NAM for hepatotoxicity based on rat primary hepatocytes, high-content imaging (HCI) and in vitro to in vivo extrapolation (IVIVE). This dataset is associated with the following publication: Shah, I., T. Antonijevic, B. Chambers, J. Harrill, and R. Thomas. Estimating Hepatotoxic Doses Using High-content Imaging in Primary Hepatocytes. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 183(2): 285-301, (2021).

Supporting information in "Saunders, L.J. and Nichols, J.W. (2023), Models Used to Predict Chemical Bioaccumulation in Fish from in Vitro Biotransformation Rates Require Accurate Estimates of Blood–Water Partitioning and Chemical Volume of Distribution. Environ Toxicol Chem, 42: 33-45. https://doi.org/10.1002/etc.5503". This dataset is associated with the following publication: Saunders, L., and J. Nichols. Models Used to Predict Chemical Bioaccumulation in Fish from in Vitro Biotransformation Rates Require Accurate Estimates of Blood–Water Partitioning and Chemical Volume of Distribution. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY. Society of Environmental Toxicology and Chemistry, Pensacola, FL, USA, 42(1): 33-45, (2023).

This paper describes the results of an international ring trial (round robin study) of in vitro methods used to measure chemical biotransformation in fish. Researchers at six laboratories in the U.S. and Europe evaluated six test chemicals (cyclohexyl salicylate, fenthion, 4-n-nonylphenol, deltamethrin, methoxychlor, and pyrene) using two in vitro systems (liver S9 fraction and isolated hepatocytes) derived from rainbow trout livers. This information was then evaluated to quantitatively characterize assay reliability (repeatability and reproducibility) and evaluate potential user bias associated with the methods. Additional calculations were performed using established models to estimate in vivo levels of hepatic clearance and predict the effects on chemical biotransformation on chemical bioaccumulation. The Science Hub dataset includes all information presented in the paper as figures and tables including, as appropriate, individual values used to calculate reported means and standard deviations. Also included are all datasets provided as Supplementary Data. This dataset is associated with the following publication: Nichols, J., K. Fay, M.J. Bernhard, I. Bischof, J. Davis, M. Halder, J. Hu, K. Johanning, H. Laue, D. Nabb, C. Schlechtriem, H. Segner, J. Swintek, J. Weeks, and M. Embry. Reliability of In Vitro methods used to measure intrinsic clearance of hydrophobic organic chemicals by rainbow trout: Results of an international ring trial. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 164(2): 563-575, (2018).

This paper describes the results of an international ring trial (round robin study) of in vitro methods used to measure chemical biotransformation in fish. Researchers at six laboratories in the U.S. and Europe evaluated six test chemicals (cyclohexyl salicylate, fenthion, 4-n-nonylphenol, deltamethrin, methoxychlor, and pyrene) using two in vitro systems (liver S9 fraction and isolated hepatocytes) derived from rainbow trout livers. This information was then evaluated to quantitatively characterize assay reliability (repeatability and reproducibility) and evaluate potential user bias associated with the methods. Additional calculations were performed using established models to estimate in vivo levels of hepatic clearance and predict the effects on chemical biotransformation on chemical bioaccumulation. The Science Hub dataset includes all information presented in the paper as figures and tables including, as appropriate, individual values used to calculate reported means and standard deviations. Also included are all datasets provided as Supplementary Data. This dataset is associated with the following publication: Nichols, J., K. Fay, M.J. Bernhard, I. Bischof, J. Davis, M. Halder, J. Hu, K. Johanning, H. Laue, D. Nabb, C. Schlechtriem, H. Segner, J. Swintek, J. Weeks, and M. Embry. Reliability of In Vitro methods used to measure intrinsic clearance of hydrophobic organic chemicals by rainbow trout: Results of an international ring trial. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 164(2): 563-575, (2018).