Description

This data set contains the necessary information to make basic, high-throughput toxicokinetic (HTTK) predictions for compounds, including Funbound.plasma, molecular weight (g/mol), logP, logMA (membrane affinity), intrinsic clearance(uL/min/10^6 cells), and pKa. These data have been compiled from multiple sources, and can be used to parameterize a variety of toxicokinetic models. See variable EPA.ref for information on the reference EPA.

Usage

Format

A data.frame containing 565 rows and 33 columns.

Author(s)

John Wambaugh

Source

Wambaugh, John F., et al. "Toxicokinetic triage for environmental chemicals." Toxicological Sciences (2015): 228-237.

References

DSStox database (https:// www.epa.gov/ncct/dsstox

EPI Suite, https://www.epa.gov/opptintr/exposure/pubs/episuite.htm

Hilal, S., Karickhoff, S. and Carreira, L. (1995). A rigorous test for SPARC's chemical reactivity models: Estimation of more than 4300 ionization pKas. Quantitative Structure-Activity Relationships 14(4), 348-355.

Honda, G. S., Pearce, R. G., Pham, L. L., Setzer, R. W., Wetmore, B. A., Sipes, N. S., ... & Wambaugh, J. F. (2019). Using the concordance of in vitro and in vivo data to evaluate extrapolation assumptions. PloS one, 14(5), e0217564.

Ito, K. and Houston, J. B. (2004). Comparison of the use of liver models for predicting drug clearance using in vitro kinetic data from hepatic microsomes and isolated hepatocytes. Pharm Res 21(5), 785-92.

Jones, O. A., Voulvoulis, N. and Lester, J. N. (2002). Aquatic environmental assessment of the top 25 English prescription pharmaceuticals. Water research 36(20), 5013-22.

Lau, Y. Y., Sapidou, E., Cui, X., White, R. E. and Cheng, K. C. (2002). Development of a novel in vitro model to predict hepatic clearance using fresh, cryopreserved, and sandwich-cultured hepatocytes. Drug Metabolism and Disposition 30(12), 1446-54.

Linakis, M. W., Sayre, R. R., Pearce, R. G., Sfeir, M. A., Sipes, N. S., Pangburn, H. A., ... & Wambaugh, J. F. (2020). Development and evaluation of a high throughput inhalation model for organic chemicals. Journal of Exposure Science & Environmental Epidemiology, 1-12.

Lombardo, F., Berellini, G., & Obach, R. S. (2018). Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 1352 drug compounds. Drug Metabolism and Disposition, 46(11), 1466-1477.

McGinnity, D. F., Soars, M. G., Urbanowicz, R. A. and Riley, R. J. (2004). Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. Drug Metabolism and Disposition 32(11), 1247-53, 10.1124/dmd.104.000026.

Naritomi, Y., Terashita, S., Kagayama, A. and Sugiyama, Y. (2003). Utility of Hepatocytes in Predicting Drug Metabolism: Comparison of Hepatic Intrinsic Clearance in Rats and Humans in Vivo and in Vitro. Drug Metabolism and Disposition 31(5), 580-588, 10.1124/dmd.31.5.580.

Obach, R. S. (1999). Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes. Drug Metabolism and Disposition 27(11), 1350-9.

Paini, Alicia; Cole, Thomas; Meinero, Maria; Carpi, Donatella; Deceuninck, Pierre; Macko, Peter; Palosaari, Taina; Sund, Jukka; Worth, Andrew; Whelan, Maurice (2020): EURL ECVAM in vitro hepatocyte clearance and blood plasma protein binding dataset for 77 chemicals. European Commission, Joint Research Centre (JRC) [Dataset] PID: https://data.europa.eu/89h/a2ff867f-db80-4acf-8e5c-e45502713bee

Paixao, P., Gouveia, L. F., & Morais, J. A. (2012). Prediction of the human oral bioavailability by using in vitro and in silico drug related parameters in a physiologically based absorption model. International journal of pharmaceutics, 429(1), 84-98.

Pirovano, Alessandra, et al. "QSARs for estimating intrinsic hepatic clearance of organic chemicals in humans." Environmental toxicology and pharmacology 42 (2016): 190-197.

Schmitt, W. (2008). General approach for the calculation of tissue to plasma partition coefficients. Toxicology in vitro : an international journal published in association with BIBRA 22(2), 457-67, 10.1016/j.tiv.2007.09.010.

Shibata, Y., Takahashi, H., Chiba, M. and Ishii, Y. (2002). Prediction of Hepatic Clearance and Availability by Cryopreserved Human Hepatocytes: An Application of Serum Incubation Method. Drug Metabolism and Disposition 30(8), 892-896, 10.1124/dmd.30.8.892.

Tonnelier, A., Coecke, S. and Zaldivar, J.-M. (2012). Screening of chemicals for human bioaccumulative potential with a physiologically based toxicokinetic model. Archives of Toxicology 86(3), 393-403, 10.1007/s00204-011-0768-0.

Uchimura, Takahide, et al. "Prediction of human blood-to-plasma drug concentration ratio." Biopharmaceutics & drug disposition 31.5-6 (2010): 286-297.

Wambaugh, J. F., Wetmore, B. A., Ring, C. L., Nicolas, C. I., Pearce, R. G., Honda, G. S., ... & Badrinarayanan, A. (2019). Assessing Toxicokinetic Uncertainty and Variability in Risk Prioritization. Toxicological Sciences, 172(2), 235-251.

Wetmore, B. A., Wambaugh, J. F., Ferguson, S. S., Sochaski, M. A., Rotroff, D. M., Freeman, K., Clewell, H. J., 3rd, Dix, D. J., Andersen, M. E., Houck, K. A., Allen, B., Judson, R. S., Singh, R., Kavlock, R. J., Richard, A. M. and Thomas, R. S. (2012). Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicological sciences : an official journal of the Society of Toxicology 125(1), 157-74, 10.1093/toxsci/kfr254.

Wetmore, B. A., Wambaugh, J. F., Ferguson, S. S., Li, L., Clewell, H. J., Judson, R. S., Freeman, K., Bao, W., Sochaski, M. A., Chu, T.-M., Black, M. B., Healy, E., Allen, B., Andersen, M. E., Wolfinger, R. D. and Thomas, R. S. (2013). Relative Impact of Incorporating Pharmacokinetics on Predicting In Vivo Hazard and Mode of Action from High-Throughput In Vitro Toxicity Assays. Toxicological Sciences 132(2), 327-346, 10.1093/toxsci/kft012.

Wetmore, B. A., Wambaugh, J. F., Allen, B., Ferguson, S. S., Sochaski, M. A., Setzer, R. W., Houck, K. A., Strope, C. L., Cantwell, K., Judson, R. S., LeCluyse, E., Clewell, H.J. III, Thomas, R.S., and Andersen, M. E. (2015). "Incorporating High-Throughput Exposure Predictions with Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing" Toxicological Sciences, kfv171.