DOI: 10.1093/toxsci/kfq220. Incorporating Human Dosimetry and Exposure into High-Throughput<i>In Vitro</i>Toxicity Screening

Incorporating Human Dosimetry and Exposure into High-ThroughputIn VitroToxicity Screening

10.1093/toxsci/kfq220

Crossref journal-article

Oxford University Press (OUP)

Toxicological Sciences (286)

Bibliography

Rotroff, D. M., Wetmore, B. A., Dix, D. J., Ferguson, S. S., Clewell, H. J., Houck, K. A., LeCluyse, E. L., Andersen, M. E., Judson, R. S., Smith, C. M., Sochaski, M. A., Kavlock, R. J., Boellmann, F., Martin, M. T., Reif, D. M., Wambaugh, J. F., & Thomas, R. S. (2010). Incorporating Human Dosimetry and Exposure into High-ThroughputIn VitroToxicity Screening. Toxicological Sciences, 117(2), 348â358.

Authors 17

Daniel M. Rotroff (first)
Barbara A. Wetmore (additional)
David J. Dix (additional)
Stephen S. Ferguson (additional)
Harvey J. Clewell (additional)
Keith A. Houck (additional)
Edward L. LeCluyse (additional)
Melvin E. Andersen (additional)
Richard S. Judson (additional)
Cornelia M. Smith (additional)
Mark A. Sochaski (additional)
Robert J. Kavlock (additional)
Frank Boellmann (additional)
Matthew T. Martin (additional)
David M. Reif (additional)
John F. Wambaugh (additional)
Russell S. Thomas (additional)

References 48 Referenced 226

10.1038/461158a / Nature / Toxicity testing gets a makeover by Abbott (2009)
{'key': 'key\n\t\t\t\t2018110206105899600_bib2', 'first-page': '91', 'article-title': 'Public availability of data on EU high production volume chemicals. Part 1', 'volume': '21', 'author': 'Allanou', 'year': '2003', 'journal-title': 'Chim. Oggi'} / Chim. Oggi / Public availability of data on EU high production volume chemicals. Part 1 by Allanou (2003)
10.1093/toxsci/kfn255 / Toxicol. Sci. / Toxicity testing in the 21st century: bringing the vision to life by Andersen (2009)
10.3109/00498259109044401 / Xenobiotica / Comparative pharmacokinetics and bioavailability of oxolinic acid and oxytetracycline in rainbow trout (Oncorhynchus mykiss) by Bjorklund (1991)
10.1016/S0378-4274(02)00367-3 / Toxicol. Lett. / The integration of data on physico-chemical properties, in vitro-derived toxicity data and physiologically based kinetic and dynamic as modelling a tool in hazard and risk assessment. A commentary by Blaauboer (2003)
10.1080/10937404.2010.483940 / J. Toxicol. Environ. Health, Part B / Biokinetic modeling and in vitro-in vivo exptrapolations by Blaauboer (2010)
10.1038/sj.embor.7400816 / EMBO Rep. / The costs of REACH. REACH is largely welcomed, but the requirement to test existing chemicals for adverse effects is not good news for all by Breithaupt (2006)
10.1289/ehp.111-a766 / Environ. Health Perspect. / REACHing for chemical safety by Brown (2003)
10.2174/156802609789630929 / Curr. Top. Med. Chem. / ADME optimization and toxicity assessment in early- and late-phase drug discovery by Caldwell (2009)
10.1078/1438-4639-00240 / Int. J. Hyg. Environ. Health / Toxicity characterization of environmental chemicals by the US National Toxicology Program: an overview by Chhabra (2003)
10.1080/10937404.2010.483947 / J. Toxicol. Environ. Health B Crit. Rev. / Advancing exposure characterization for chemical evaluation and risk assessment by Cohen Hubal (2010)
10.1126/science.1154619 / Science / Toxicology. Transforming environmental health protection by Collins (2008)
10.1111/j.1539-6924.1995.tb00095.x / Risk Anal. / Calculation of benchmark dose from continuous data by Crump (1995)
10.1517/17425255.3.6.865 / Expert Opin. Drug Metab. Toxicol. / Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolation by De Buck (2007)
10.1093/toxsci/kfl103 / Toxicol. Sci. / The ToxCast program for prioritizing toxicity testing of environmental chemicals by Dix (2007)
10.1177/0960327107087801 / Hum. Exp. Toxicol. / Concept of REACH and impact on evaluation of chemicals by Foth (2008)
10.1093/toxsci/70.1.120 / Toxicol. Sci. / An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion by Gentry (2002)
10.1007/s00204-004-0577-9 / Arch. Toxicol. / Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation by Hofer (2004)
10.1093/toxsci/kfn258 / Toxicol. Sci. / Forum Series: the “Vision” for Toxicity Testing in the 21st Century: promises and conundrums by Holsapple (2009)
10.1517/17425250802691074 / Expert Opin. Drug Metab. Toxicol / The Simcyp((R)) Population-based ADME Simulator by Jamei (2009)
10.1124/dmd.104.000125 / Drug Metab. Dispos. / Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations by Jones (2004)
10.1289/ehp.0800168 / Environ. Health Perspect. / The toxicity data landscape for environmental chemicals by Judson (2009)
10.1289/ehp.0901392 / Environ. Health Perspect. / In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project by Judson (2010)
10.1111/j.1539-6924.2008.01168.x / Risk Anal. / Toxicity testing in the 21st century: implications for human health risk assessment by Kavlock (2009)
10.14573/altex.2008.3.213 / ALTEX / Non-animal methodologies within biomedical research and toxicity testing by Knight (2008)
10.3109/00498257409049349 / Xenobiotica / Absorption and excretion of 2,4-dichlorophenoxyacetic acid in man by Kohli (1974)
10.1111/j.1539-6924.2008.01150.x / Risk Anal. / Toxicity testing in the 21st century: implications for human health risk assessment by Krewski (2009)
10.1016/S0009-2797(99)00088-5 / Chem. Biol. Interact. / Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential by Li (1999)
10.1080/10937404.2010.483952 / J. Toxicol. Environ. Health, Part B / Implementing the National Academy’s vision and strategy for toxicity testing: opportunities and challenges under the U.S. Toxic Substances Control Act by Locke (2010)
10.1289/ehp.0800074 / Environ. Health Perspect. / Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database by Martin (2009)
{'key': 'key\n\t\t\t\t2018110206105899600_bib31', 'first-page': '1316', 'article-title': 'Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans', 'volume': '29', 'author': 'Naritomi', 'year': '2001', 'journal-title': 'Drug Metab. Dispos.'} / Drug Metab. Dispos. / Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans by Naritomi (2001)
10.1111/j.1365-2885.1996.tb00054.x / J. Vet. Pharmacol. Ther. / Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs by Nielsen (1996)
{'volume-title': 'Risk Assessment in the Federal Government: Managing the Process', 'year': '1983', 'author': 'National Research Council (NRC)', 'key': 'key\n\t\t\t\t2018110206105899600_bib33'} / Risk Assessment in the Federal Government: Managing the Process by National Research Council (NRC) (1983)
{'volume-title': 'Toxicity Testing in the 21st Century: A Vision and a Strategy', 'year': '2007', 'author': 'National Research Council (NRC)', 'key': 'key\n\t\t\t\t2018110206105899600_bib34'} / Toxicity Testing in the 21st Century: A Vision and a Strategy by National Research Council (NRC) (2007)
{'volume-title': 'NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A', 'year': '2008', 'author': 'National Toxicology Program (NTP)', 'key': 'key\n\t\t\t\t2018110206105899600_bib48'} / NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A by National Toxicology Program (NTP) (2008)
10.1016/S0090-9556(24)14938-0 / Drug Metab. Dispos. / 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 by Obach (1999)
10.1080/00984100290071171 / J. Toxicol. Environ. Health A / Comparison of models for the estimation of biological partition coefficients by Payne (2002)
10.1002/jps.10005 / J. Pharm. Sci. / Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution by Poulin (2002)
10.1038/nrd2173 / Nat. Rev. Drug Discov. / Simulation and prediction of in vivo drug metabolism in human populations from in vitro data by Rostami-Hodjegan (2007)
10.1007/BF01059626 / J. Pharmacokinet. Biopharm. / Clearance concepts in pharmacokinetics by Rowland (1973)
10.1053/j.ajkd.2003.09.026 / Am. J. Kidney Dis. / Measured and estimated GFR in healthy potential kidney donors by Rule (2004)
10.1016/0300-483X(77)90018-X / Toxicology / The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man by Sauerhoff (1977)
10.1080/00498250600761662 / Xenobiotica / Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling by Shiran (2006)
{'volume-title': 'Chemical Hazard Data Availability Study: What Do We Really Know about the Safety of High Production Volume Chemicals', 'year': '1998', 'author': 'U.S. Environmental Protection Agency (EPA)', 'key': 'key\n\t\t\t\t2018110206105899600_bib43'} / Chemical Hazard Data Availability Study: What Do We Really Know about the Safety of High Production Volume Chemicals by U.S. Environmental Protection Agency (EPA) (1998)
10.1016/j.toxlet.2006.01.017 / Toxicol. Lett. / Prediction of in vivo embryotoxic effect levels with a combination of in vitro studies and PBPK modelling by Verwei (2006)
10.1021/tx025548t / Chem. Res. Toxicol. / Metabolism and kinetics of bisphenol a in humans at low doses following oral administration by Volkel (2002)
10.1002/jps.21317 / J. Pharm. Sci. / Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding by Waters (2008)
10.1289/ehp.0800404 / Environ. Health Perspect. / Toward a new U.S. chemicals policy: rebuilding the foundation to advance new science, green chemistry, and environmental health by Wilson (2009)

Dates

Type	When
Created	15 years, 1 month ago (July 16, 2010, 8:49 p.m.)
Deposited	6 months, 1 week ago (Feb. 22, 2025, 8:47 p.m.)
Indexed	22 hours, 46 minutes ago (Sept. 4, 2025, 9:37 a.m.)
Issued	15 years, 1 month ago (July 16, 2010)
Published	15 years, 1 month ago (July 16, 2010)
Published Online	15 years, 1 month ago (July 16, 2010)
Published Print	14 years, 11 months ago (Oct. 1, 2010)

Funders 1

The Hamner Institutes for Health Sciences
Awards1
1. EPA CR83323601-DESE

BibTeX

@article{Rotroff_2010, title={Incorporating Human Dosimetry and Exposure into High-ThroughputIn VitroToxicity Screening}, volume={117}, ISSN={1096-0929}, url={http://dx.doi.org/10.1093/toxsci/kfq220}, DOI={10.1093/toxsci/kfq220}, number={2}, journal={Toxicological Sciences}, publisher={Oxford University Press (OUP)}, author={Rotroff, Daniel M. and Wetmore, Barbara A. and Dix, David J. and Ferguson, Stephen S. and Clewell, Harvey J. and Houck, Keith A. and LeCluyse, Edward L. and Andersen, Melvin E. and Judson, Richard S. and Smith, Cornelia M. and Sochaski, Mark A. and Kavlock, Robert J. and Boellmann, Frank and Martin, Matthew T. and Reif, David M. and Wambaugh, John F. and Thomas, Russell S.}, year={2010}, month=jul, pages={348–358} }

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      "DOI": "10.1038/461158a",
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      "author": "Abbott",
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      "journal-title": "Nature"
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    {
      "key": "key\n\t\t\t\t2018110206105899600_bib2",
      "first-page": "91",
      "article-title": "Public availability of data on EU high production volume chemicals. Part 1",
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      "volume": "107",
      "author": "Andersen",
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      "author": "Bjorklund",
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      "first-page": "161",
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      "article-title": "The integration of data on physico-chemical properties, in vitro-derived toxicity data and physiologically based kinetic and dynamic as modelling a tool in hazard and risk assessment. A commentary",
      "volume": "138",
      "author": "Blaauboer",
      "year": "2003",
      "journal-title": "Toxicol. Lett."
    },
    {
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      "first-page": "242",
      "DOI": "10.1080/10937404.2010.483940",
      "article-title": "Biokinetic modeling and in vitro-in vivo exptrapolations",
      "volume": "13",
      "author": "Blaauboer",
      "year": "2010",
      "journal-title": "J. Toxicol. Environ. Health, Part B"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib7",
      "doi-asserted-by": "crossref",
      "first-page": "968",
      "DOI": "10.1038/sj.embor.7400816",
      "article-title": "The costs of REACH. REACH is largely welcomed, but the requirement to test existing chemicals for adverse effects is not good news for all",
      "volume": "7",
      "author": "Breithaupt",
      "year": "2006",
      "journal-title": "EMBO Rep."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib8",
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      "first-page": "A766",
      "DOI": "10.1289/ehp.111-a766",
      "article-title": "REACHing for chemical safety",
      "volume": "111",
      "author": "Brown",
      "year": "2003",
      "journal-title": "Environ. Health Perspect."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib9",
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      "first-page": "965",
      "DOI": "10.2174/156802609789630929",
      "article-title": "ADME optimization and toxicity assessment in early- and late-phase drug discovery",
      "volume": "9",
      "author": "Caldwell",
      "year": "2009",
      "journal-title": "Curr. Top. Med. Chem."
    },
    {
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      "first-page": "437",
      "DOI": "10.1078/1438-4639-00240",
      "article-title": "Toxicity characterization of environmental chemicals by the US National Toxicology Program: an overview",
      "volume": "206",
      "author": "Chhabra",
      "year": "2003",
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    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib11",
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      "first-page": "299",
      "DOI": "10.1080/10937404.2010.483947",
      "article-title": "Advancing exposure characterization for chemical evaluation and risk assessment",
      "volume": "13",
      "author": "Cohen Hubal",
      "year": "2010",
      "journal-title": "J. Toxicol. Environ. Health B Crit. Rev."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib12",
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      "first-page": "906",
      "DOI": "10.1126/science.1154619",
      "article-title": "Toxicology. Transforming environmental health protection",
      "volume": "319",
      "author": "Collins",
      "year": "2008",
      "journal-title": "Science"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib13",
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      "volume": "15",
      "author": "Crump",
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      "journal-title": "Risk Anal."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib14",
      "doi-asserted-by": "crossref",
      "first-page": "865",
      "DOI": "10.1517/17425255.3.6.865",
      "article-title": "Physiologically based approaches towards the prediction of pharmacokinetics: in vitro-in vivo extrapolation",
      "volume": "3",
      "author": "De Buck",
      "year": "2007",
      "journal-title": "Expert Opin. Drug Metab. Toxicol."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib15",
      "doi-asserted-by": "crossref",
      "first-page": "5",
      "DOI": "10.1093/toxsci/kfl103",
      "article-title": "The ToxCast program for prioritizing toxicity testing of environmental chemicals",
      "volume": "95",
      "author": "Dix",
      "year": "2007",
      "journal-title": "Toxicol. Sci."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib16",
      "doi-asserted-by": "crossref",
      "first-page": "5",
      "DOI": "10.1177/0960327107087801",
      "article-title": "Concept of REACH and impact on evaluation of chemicals",
      "volume": "27",
      "author": "Foth",
      "year": "2008",
      "journal-title": "Hum. Exp. Toxicol."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib17",
      "doi-asserted-by": "crossref",
      "first-page": "120",
      "DOI": "10.1093/toxsci/70.1.120",
      "article-title": "An approach for the quantitative consideration of genetic polymorphism data in chemical risk assessment: examples with warfarin and parathion",
      "volume": "70",
      "author": "Gentry",
      "year": "2002",
      "journal-title": "Toxicol. Sci."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib18",
      "doi-asserted-by": "crossref",
      "first-page": "549",
      "DOI": "10.1007/s00204-004-0577-9",
      "article-title": "Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation",
      "volume": "78",
      "author": "Hofer",
      "year": "2004",
      "journal-title": "Arch. Toxicol."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib19",
      "doi-asserted-by": "crossref",
      "first-page": "307",
      "DOI": "10.1093/toxsci/kfn258",
      "article-title": "Forum Series: the \u201cVision\u201d for Toxicity Testing in the 21st Century: promises and conundrums",
      "volume": "107",
      "author": "Holsapple",
      "year": "2009",
      "journal-title": "Toxicol. Sci."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib20",
      "doi-asserted-by": "crossref",
      "first-page": "211",
      "DOI": "10.1517/17425250802691074",
      "article-title": "The Simcyp((R)) Population-based ADME Simulator",
      "volume": "5",
      "author": "Jamei",
      "year": "2009",
      "journal-title": "Expert Opin. Drug Metab. Toxicol"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib21",
      "doi-asserted-by": "crossref",
      "first-page": "973",
      "DOI": "10.1124/dmd.104.000125",
      "article-title": "Substrate depletion approach for determining in vitro metabolic clearance: time dependencies in hepatocyte and microsomal incubations",
      "volume": "32",
      "author": "Jones",
      "year": "2004",
      "journal-title": "Drug Metab. Dispos."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib22",
      "doi-asserted-by": "crossref",
      "first-page": "685",
      "DOI": "10.1289/ehp.0800168",
      "article-title": "The toxicity data landscape for environmental chemicals",
      "volume": "117",
      "author": "Judson",
      "year": "2009",
      "journal-title": "Environ. Health Perspect."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib23",
      "doi-asserted-by": "crossref",
      "first-page": "485",
      "DOI": "10.1289/ehp.0901392",
      "article-title": "In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project",
      "volume": "118",
      "author": "Judson",
      "year": "2010",
      "journal-title": "Environ. Health Perspect."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib24",
      "doi-asserted-by": "crossref",
      "first-page": "485",
      "DOI": "10.1111/j.1539-6924.2008.01168.x",
      "article-title": "Toxicity testing in the 21st century: implications for human health risk assessment",
      "volume": "29",
      "author": "Kavlock",
      "year": "2009",
      "journal-title": "Risk Anal."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib25",
      "doi-asserted-by": "crossref",
      "first-page": "213",
      "DOI": "10.14573/altex.2008.3.213",
      "article-title": "Non-animal methodologies within biomedical research and toxicity testing",
      "volume": "25",
      "author": "Knight",
      "year": "2008",
      "journal-title": "ALTEX"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib26",
      "doi-asserted-by": "crossref",
      "first-page": "97",
      "DOI": "10.3109/00498257409049349",
      "article-title": "Absorption and excretion of 2,4-dichlorophenoxyacetic acid in man",
      "volume": "4",
      "author": "Kohli",
      "year": "1974",
      "journal-title": "Xenobiotica"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib27",
      "doi-asserted-by": "crossref",
      "first-page": "474",
      "DOI": "10.1111/j.1539-6924.2008.01150.x",
      "article-title": "Toxicity testing in the 21st century: implications for human health risk assessment",
      "volume": "29",
      "author": "Krewski",
      "year": "2009",
      "journal-title": "Risk Anal."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib28",
      "doi-asserted-by": "crossref",
      "first-page": "17",
      "DOI": "10.1016/S0009-2797(99)00088-5",
      "article-title": "Cryopreserved human hepatocytes: characterization of drug-metabolizing enzyme activities and applications in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential",
      "volume": "121",
      "author": "Li",
      "year": "1999",
      "journal-title": "Chem. Biol. Interact."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib29",
      "doi-asserted-by": "crossref",
      "first-page": "376",
      "DOI": "10.1080/10937404.2010.483952",
      "article-title": "Implementing the National Academy\u2019s vision and strategy for toxicity testing: opportunities and challenges under the U.S. Toxic Substances Control Act",
      "volume": "13",
      "author": "Locke",
      "year": "2010",
      "journal-title": "J. Toxicol. Environ. Health, Part B"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib30",
      "doi-asserted-by": "crossref",
      "first-page": "392",
      "DOI": "10.1289/ehp.0800074",
      "article-title": "Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database",
      "volume": "117",
      "author": "Martin",
      "year": "2009",
      "journal-title": "Environ. Health Perspect."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib31",
      "first-page": "1316",
      "article-title": "Prediction of human hepatic clearance from in vivo animal experiments and in vitro metabolic studies with liver microsomes from animals and humans",
      "volume": "29",
      "author": "Naritomi",
      "year": "2001",
      "journal-title": "Drug Metab. Dispos."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib32",
      "doi-asserted-by": "crossref",
      "first-page": "305",
      "DOI": "10.1111/j.1365-2885.1996.tb00054.x",
      "article-title": "Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs",
      "volume": "19",
      "author": "Nielsen",
      "year": "1996",
      "journal-title": "J. Vet. Pharmacol. Ther."
    },
    {
      "volume-title": "Risk Assessment in the Federal Government: Managing the Process",
      "year": "1983",
      "author": "National Research Council (NRC)",
      "key": "key\n\t\t\t\t2018110206105899600_bib33"
    },
    {
      "volume-title": "Toxicity Testing in the 21st Century: A Vision and a Strategy",
      "year": "2007",
      "author": "National Research Council (NRC)",
      "key": "key\n\t\t\t\t2018110206105899600_bib34"
    },
    {
      "volume-title": "NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A",
      "year": "2008",
      "author": "National Toxicology Program (NTP)",
      "key": "key\n\t\t\t\t2018110206105899600_bib48"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib35",
      "doi-asserted-by": "crossref",
      "first-page": "1350",
      "DOI": "10.1016/S0090-9556(24)14938-0",
      "article-title": "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",
      "volume": "27",
      "author": "Obach",
      "year": "1999",
      "journal-title": "Drug Metab. Dispos."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib36",
      "doi-asserted-by": "crossref",
      "first-page": "897",
      "DOI": "10.1080/00984100290071171",
      "article-title": "Comparison of models for the estimation of biological partition coefficients",
      "volume": "65",
      "author": "Payne",
      "year": "2002",
      "journal-title": "J. Toxicol. Environ. Health A"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib37",
      "doi-asserted-by": "crossref",
      "first-page": "129",
      "DOI": "10.1002/jps.10005",
      "article-title": "Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution",
      "volume": "91",
      "author": "Poulin",
      "year": "2002",
      "journal-title": "J. Pharm. Sci."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib38",
      "doi-asserted-by": "crossref",
      "first-page": "140",
      "DOI": "10.1038/nrd2173",
      "article-title": "Simulation and prediction of in vivo drug metabolism in human populations from in vitro data",
      "volume": "6",
      "author": "Rostami-Hodjegan",
      "year": "2007",
      "journal-title": "Nat. Rev. Drug Discov."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib39",
      "doi-asserted-by": "crossref",
      "first-page": "123",
      "DOI": "10.1007/BF01059626",
      "article-title": "Clearance concepts in pharmacokinetics",
      "volume": "1",
      "author": "Rowland",
      "year": "1973",
      "journal-title": "J. Pharmacokinet. Biopharm."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib40",
      "doi-asserted-by": "crossref",
      "first-page": "112",
      "DOI": "10.1053/j.ajkd.2003.09.026",
      "article-title": "Measured and estimated GFR in healthy potential kidney donors",
      "volume": "43",
      "author": "Rule",
      "year": "2004",
      "journal-title": "Am. J. Kidney Dis."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib41",
      "doi-asserted-by": "crossref",
      "first-page": "3",
      "DOI": "10.1016/0300-483X(77)90018-X",
      "article-title": "The fate of 2,4-dichlorophenoxyacetic acid (2,4-D) following oral administration to man",
      "volume": "8",
      "author": "Sauerhoff",
      "year": "1977",
      "journal-title": "Toxicology"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib42",
      "doi-asserted-by": "crossref",
      "first-page": "567",
      "DOI": "10.1080/00498250600761662",
      "article-title": "Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling",
      "volume": "36",
      "author": "Shiran",
      "year": "2006",
      "journal-title": "Xenobiotica"
    },
    {
      "volume-title": "Chemical Hazard Data Availability Study: What Do We Really Know about the Safety of High Production Volume Chemicals",
      "year": "1998",
      "author": "U.S. Environmental Protection Agency (EPA)",
      "key": "key\n\t\t\t\t2018110206105899600_bib43"
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib44",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1016/j.toxlet.2006.01.017",
      "article-title": "Prediction of in vivo embryotoxic effect levels with a combination of in vitro studies and PBPK modelling",
      "volume": "165",
      "author": "Verwei",
      "year": "2006",
      "journal-title": "Toxicol. Lett."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib45",
      "doi-asserted-by": "crossref",
      "first-page": "1281",
      "DOI": "10.1021/tx025548t",
      "article-title": "Metabolism and kinetics of bisphenol a in humans at low doses following oral administration",
      "volume": "15",
      "author": "Volkel",
      "year": "2002",
      "journal-title": "Chem. Res. Toxicol."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib46",
      "doi-asserted-by": "crossref",
      "first-page": "4586",
      "DOI": "10.1002/jps.21317",
      "article-title": "Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding",
      "volume": "97",
      "author": "Waters",
      "year": "2008",
      "journal-title": "J. Pharm. Sci."
    },
    {
      "key": "key\n\t\t\t\t2018110206105899600_bib47",
      "doi-asserted-by": "crossref",
      "first-page": "1202",
      "DOI": "10.1289/ehp.0800404",
      "article-title": "Toward a new U.S. chemicals policy: rebuilding the foundation to advance new science, green chemistry, and environmental health",
      "volume": "117",
      "author": "Wilson",
      "year": "2009",
      "journal-title": "Environ. Health Perspect."
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