Package 'invitroTKdata'

Title: In Vitro Toxicokinetic Data Processed with the 'invitroTKstats' Pipeline
Description: A collection of datasets containing a variety of in vitro toxicokinetic measurements including -- but not limited to -- chemical fraction unbound in the presence of plasma (f_up), intrinsic hepatic clearance (Clint, uL/min/million hepatocytes), and membrane permeability for oral absorption (Caco2). The datasets provided by the package were processed and analyzed with the companion 'invitroTKstats' package.
Authors: Sarah E. Davidson-Fritz [aut] (ORCID: <https://orcid.org/0000-0002-2891-9380>), Caroline Ring [cre] (ORCID: <https://orcid.org/0000-0002-0463-1251>), John Wambaugh [aut] (ORCID: <https://orcid.org/0000-0002-4024-534X>), Lindsay Knupp [ctb], Barbara A. Wetmore [ctb] (ORCID: <https://orcid.org/0000-0002-6878-5348>), Anna Kreutz [ctb] (ORCID: <https://orcid.org/0000-0002-7787-0683>), Marci Smeltz [ctb] (ORCID: <https://orcid.org/0000-0001-9723-8696>), David Crizer [ctb], U.S. Federal Government [cph] (Copyright holder of this package)
Maintainer: Caroline Ring <[email protected]>
License: MIT + file LICENSE
Version: 0.0.2
Built: 2026-05-07 09:32:48 UTC
Source: https://github.com/usepa/invitrotkdata

Help Index

Crizer et al. (2024) Intrinsic Hepatic Clearance Level-2 Data Set

Description

Mass Spectrometry measurements of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr. Crizer.

Usage

crizer2024.clint

Format

A level-2 data.frame with 7,070 rows and 24 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of Clint sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Hep.Density

The density (units of millions of hepatocytes per mL) hepatocytes in the in vitro incubation

Std.Conc

Concentration of analytic standard (for calibration curve) (uM)

Clint.Assay.Conc

Intended initial concentration of chemical (uM)

Time

Time when sample was measured (h)

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis)

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Crizer DM, Rice JR, Smeltz MG, Lavrich KS, Ravindra K, Wambaugh JF, DeVito M, Wetmore BA (2024). “In Vitro Hepatic Clearance Evaluations of Per-and Polyfluoroalkyl Substances (PFAS) across Multiple Structural Categories.” Toxics, 12(9), 672.

Crizer et al. (2024) Intrinsic Hepatic Clearance Level-3 Data Set

Description

Frequentist estimates of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr. Crizer.

Usage

crizer2024.clint.L3

Format

A level-3 data.frame with 60 rows and 13 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration – usually the date

Clint

Frequentist point estimate for intrinsic hepatic clearance (Clint)

Clint.pValue

p-value of the estimated Clint value

Fit

Test nominal concentrations in the linear regression fit

AIC

Akaike Information Criterion (AIC) for the linear regression fit

AIC.Null

Akaike Information Criterion of the exponential decay assuming a constant rate of decay

Clint.1

Intrinsic hepatic clearance at 1 uM (frequentist point estimate)

Clint.10

Intrinsic hepatic clearance at 10 uM (frequentist point estimate)

AIC.Sat

Akaike Information Criterion of the exponential decay with a saturation probability

Sat.pValue

p-value of exponential decay with a saturation probability

References

Crizer DM, Rice JR, Smeltz MG, Lavrich KS, Ravindra K, Wambaugh JF, DeVito M, Wetmore BA (2024). “In Vitro Hepatic Clearance Evaluations of Per-and Polyfluoroalkyl Substances (PFAS) across Multiple Structural Categories.” Toxics, 12(9), 672.

Crizer et al. (2024) Intrinsic Hepatic Clearance Level-4 Data Set

Description

Bayesian estimates of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr. Crizer.

Usage

crizer2024.clint.L4

Format

A level-4 data.frame with 60 rows and 12 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Clint.1.Med

Posterior median intrinsic hepatic clearance at 1 uM

Clint.1.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 1 uM (lower credible interval bound)

Clint.1.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 1 uM (upper credible interval bound)

Clint.10.Med

Posterior median intrinsic hepatic clearance at 10 uM

Clint.10.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 10 uM (lower credible interval bound)

Clint.10.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 10 uM (upper credible interval bound)

Clint.pValue

Probability that a chemical concentration decrease is observed

Sat.pValue

Probability that a lower Clint is observed at a higher concentration, i.e. saturation probability

degrades.pValue

Probability of abiotic degradation

References

Crizer DM, Rice JR, Smeltz MG, Lavrich KS, Ravindra K, Wambaugh JF, DeVito M, Wetmore BA (2024). “In Vitro Hepatic Clearance Evaluations of Per-and Polyfluoroalkyl Substances (PFAS) across Multiple Structural Categories.” Toxics, 12(9), 672.

Kreutz et al. (2023) Intrinsic Hepatic Clearance Level-2 Data Set

Description

Mass Spectrometry measurements of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.clint

Format

A level-2 data.frame with 5,800 rows and 25 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of Clint sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

Std.Conc

Concentration of analytic standard (for calibration curve) (uM)

Clint.Assay.Conc

Intended initial concentration of chemical (uM)

Time

Time when sample was measured (h)

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Hep.Density

The density (units of millions of hepatocytes per mL) hepatocytes in the in vitro incubation

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis)

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Shibata Y, Takahashi H, Chiba M, 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.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Kreutz et al. (2023) Intrinsic Hepatic Clearance Level-3 Data Set

Description

Frequentist estimates of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.clint.L3

Format

A level-3 data.frame with 25 rows and 13 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration – usually the date

Clint

Frequentist point estimate for intrinsic hepatic clearance (Clint)

Clint.pValue

p-value of the estimated Clint value

Fit

Test nominal concentrations in the linear regression fit

AIC

Akaike Information Criterion (AIC) for the linear regression fit

AIC.Null

Akaike Information Criterion of the exponential decay assuming a constant rate of decay

Clint.1

Intrinsic hepatic clearance at 1 uM (frequentist point estimate)

Clint.10

Intrinsic hepatic clearance at 10 uM (frequentist point estimate)

AIC.Sat

Akaike Information Criterion of the exponential decay with a saturation probability

Sat.pValue

p-value of exponential decay with a saturation probability

References

Shibata Y, Takahashi H, Chiba M, 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.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Kreutz et al. (2023) Intrinsic Hepatic Clearance Level-4 Data Set

Description

Bayesian estimates of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocyte suspensions. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.clint.L4

Format

A level-4 data.frame with 25 rows and 12 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Clint.1.Med

Posterior median intrinsic hepatic clearance at 1 uM

Clint.1.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 1 uM (lower credible interval bound)

Clint.1.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 1 uM (upper credible interval bound)

Clint.10.Med

Posterior median intrinsic hepatic clearance at 10 uM

Clint.10.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 10 uM (lower credible interval bound)

Clint.10.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 10 uM (upper credible interval bound)

Clint.pValue

Probability that a chemical concentration decrease is observed

Sat.pValue

Probability that a lower Clint is observed at a higher concentration, i.e. saturation probability

degrades.pValue

Probability of abiotic degradation

References

Shibata Y, Takahashi H, Chiba M, 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.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Kreutz et al. (2023) Ultracentrifugation Level-2 Data Set

Description

Mass Spectrometry measurements of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.uc

Format

A level-2 data.frame with 2,955 rows and 23 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of UC sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

Standard.Conc

Concentration of analytic standard (for calibration curve) (uM)

UC.Assay.T1.Conc

Intended concentration of chemical intended in T1 sample (uM)

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Series

Identier for replicate series of UC measurements

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Kreutz et al. (2023) Ultracentrifugation Level-3 Data Set

Description

Frequentist estimates of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.uc.L3

Format

A level-3 data.frame with 73 rows and 5 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration – usually the date

Fup

Frequentist point estimate for fraction unbound in plasma (fup)

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Kreutz et al. (2023) Ultracentrifugation Level-4 Data Set

Description

Bayesian estimates of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Anna Kreutz and Barbara Wetmore.

Usage

kreutz2023.uc.L4

Format

A level-4 data.frame with 52 rows and 13 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Fstable.Med

Posterior median chemical stability fraction

Fstable.Low

Posterior 2.5th quantile chemical stability fraction (lower credible interval bound)

Fstable.High

Posterior 97.5th quantile chemical stability fraction (upper credible interval bound)

Fup.Med

Posterior median fraction unbound in plasma

Fup.Low

Posterior 2.5th quantile of fraction unbound in plasma (lower credible interval bound)

Fup.High

Posterior 97.5th quantile of fraction unbound in plasma (upper credible interval bound)

Fup.point

Point estimate of fraction unbound in plasma

Unstable

Qualitative determination of chemical stability. "Y" indicates observed chemical stability.

Uncertain

Qualitative determination of uncertainty about chemical stability. "Y" indicates uncertainty in observed chemical stability.

CV

Coefficient of variance

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Kreutz A, Clifton MS, Henderson WM, Smeltz MG, Phillips M, Wambaugh JF, Wetmore BA (2023). “Category-Based Toxicokinetic Evaluations of Data-Poor Per- and Polyfluoroalkyl Substances (PFAS) using Gas Chromatography Coupled with Mass Spectrometry.” Toxics, 11(5), 463.

Smeltz et al. (2023) Intrinsic Hepatic Clearance Level-2 Data Set

Description

Mass Spectrometry measurements of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocytes. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.clint

Format

A level-2 data.frame with 625 rows and 24 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of Clint sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

Std.Conc

Concentration of analytic standard (for calibration curve) (uM)

Clint.Assay.Conc

Intended initial concentration of chemical (uM)

Time

Time when sample was measured (h)

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Hep.Density

The density (units of millions of hepatocytes per mL) hepatocytes in the in vitro incubation

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level0 data table)

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Shibata Y, Takahashi H, Chiba M, 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.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Intrinsic Hepatic Clearance Level-3 Data Set

Description

Frequentist estimate of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocytes. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.clint.L3

Format

A level-3 data.frame with 6 rows and 13 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration – usually the date

Clint

Frequentist point estimate for intrinsic hepatic clearance (Clint)

Clint.pValue

p-value of the estimated Clint value

Fit

Test nominal concentrations in the linear regression fit

AIC

Akaike Information Criterion (AIC) for the linear regression fit

AIC.Null

Akaike Information Criterion of the exponential decay assuming a constant rate of decay

Clint.1

Intrinsic hepatic clearance at 1 uM (frequentist point estimate)

Clint.10

Intrinsic hepatic clearance at 10 uM (frequentist point estimate)

AIC.Sat

Akaike Information Criterion of the exponential decay with a saturation probability

Sat.pValue

p-value of exponential decay with a saturation probability

References

Shibata Y, Takahashi H, Chiba M, 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.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Intrinsic Hepatic Clearance Level-4 Data Set

Description

Bayesian estimate of intrinsic hepatic clearance (Clint) for cryopreserved pooled human hepatocytes. Chemicals were per- and polyfluoroalkyl substance (PFAS) samples. The experiments were led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.clint.L4

Format

A level-4 data.frame with 7 rows and 12 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Clint.1.Med

Posterior median intrinsic hepatic clearance at 1 uM

Clint.1.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 1 uM (lower credible interval bound)

Clint.1.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 1 uM (upper credible interval bound)

Clint.10.Med

Posterior median intrinsic hepatic clearance at 10 uM

Clint.10.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 10 uM (lower credible interval bound)

Clint.10.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 10 uM (upper credible interval bound)

Clint.pValue

Probability that a chemical concentration decrease is observed

Sat.pValue

Probability that a lower Clint is observed at a higher concentration, i.e. saturation probability

degrades.pValue

Probability of abiotic degradation

References

Shibata Y, Takahashi H, Chiba M, 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.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Rapid Equilibrium Dialysis Level-2 Data Set

Description

Mass Spectrometry measurements of plasma protein binding measured by rapid equilibrium dialysis (RED) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.red

Format

A level-2 data.frame with 3,955 rows and 25 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of RED sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

Std.Conc

Concentration of analytic standard (for calibration curve) (uM)

Test.Nominal.Conc

Intended concentration of chemical introduced into RED plate (uM)

Percent.Physiologic.Plasma

Percent of physiological plasma concentration in RED plate (in percent)

Time

Time of sample measurement (h)

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Replicate

Identifier for replicate series of RED measurements

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Rapid Equilibrium Dialysis Level-3 Data Set

Description

Frequentist estimate of plasma protein binding measured by rapid equilibrium dialysis (RED) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.red.L3

Format

A level-3 data.frame with 15 rows and 4 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Calibration

Identifier for mass spectrometry calibration – usually the date

Fup

Frequentist point estimate for fraction unbound in plasma (fup)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Rapid Equilibrium Dialysis Level-4 Data Set

Description

Bayesian estimate of plasma protein binding measured by rapid equilibrium dialysis (RED) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.red.L4

Format

A level-4 data.frame with 15 rows and 7 variables:

Compound.Name

Compound name

Lab.Compound.Name

Compound as described in the laboratory

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Fup.point

Point estimate of fraction unbound in plasma

Fup.Med

Posterior median estimate of fraction unbound in plasma

Fup.Low

Posterior 2.5th quantile of fraction unbound in plasma (lower credible interval bound)

Fup.High

Posterior 97.5th quantile of fraction unbound in plasma (upper credible interval bound)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Ultracentrifugation Level-2 Data Set

Description

Mass Spectrometry measurements of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.uc

Format

A level-2 data.frame with 10,133 rows and 23 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of UC sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

Standard.Conc

Concentration of analytic standard (for calibration curve) (uM)

UC.Assay.T1.Conc

Intended concentration of chemical in T1 sample (uM)

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Series

Identifier for replicate series of UC measurements

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Ultracentrifugation Level-3 Data Set

Description

Frequentist estimate of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.uc.L3

Format

A level-3 data.frame with 107 rows and 5 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration – usually the date

Fup

Frequentist point estimate for fraction unbound in plasma (fup)

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Smeltz et al. (2023) Ultracentrifugation Level-4 Data Set

Description

Bayesian estimate of plasma protein binding measured by ultracentrifugation (UC) for per- and poly-fluorinated alkyl substance (PFAS) samples from experiments led by Dr.s Marci Smeltz and Barbara Wetmore.

Usage

smeltz2023.uc.L4

Format

A level-4 data.frame with 69 rows and 7 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Fup.Med

Posterior median fraction unbound in plasma

Fup.Low

Posterior 2.5th quantile of fraction unbound in plasma (lower credible interval bound)

Fup.High

Posterior 97.5th quantile of fraction unbound in plasma (upper credible interval bound)

Fup.point

Point estimate of fraction unbound in plasma

References

Howard ML, Hill JJ, Galluppi GR, McLean MA (2010). “Plasma protein binding in drug discovery and development.” Combinatorial chemistry & high throughput screening, 13(2), 170–187.

Smeltz M, Wambaugh JF, Wetmore BA (2023). “Plasma Protein Binding Evaluations of Per- and Polyfluoroalkyl Substances for Category-Based Toxicokinetic Assessment.” Chemical Research in Toxicology, 36(6), 870–881.

Wambaugh et al. (2019) Intrinsic Hepatic Clearance Level-2 Data Set

Description

Mass spectrometry measurements of intrinsic hepatic clearance (Clint) measured using in vitro suspensions of pooled primary human hepatocytes (Shibata et al. 2002).

Usage

wambaugh2019.clint

Format

A data.frame with 22898 rows and 26 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of Clint sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration – usually the date

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area of internal standard (pixels)

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Time

Time when sample was measured (h)

Test.Compound.Conc

Measured concentration of analytic standard (for calibration curve) (uM)

Test.Nominal.Conc

Expected initial concentration of chemical added to donor side (uM)

Hep.Density

The density (units of millions of hepatocytes per mL) hepatocytes in the in vitro incubation

Biological.Replicates

Identifier for measurements of multiple samples with the same analyte

Technical.Replicates

Identifier for measurements of one sample of a compound

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

Source

Wambaugh et al. (2019)

References

Shibata Y, Takahashi H, Chiba M, 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.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.

Wambaugh et al. (2019) Intrinsic Hepatic Clearance Level-3 Data Set

Description

Frequentist estimate of intrinsic hepatic clearance (Clint) measured using in vitro suspensions of pooled primary human hepatocytes (Shibata et al. 2002).

Usage

wambaugh2019.clint.L3

Format

A data.frame with 473 rows and 13 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemical Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Calibration

Identifier for mass spectrometry calibration - usually the date

Clint

Frequentist point estimate for intrinsic hepatic clearance (Clint)

Clint.pValue

p-value of the estimated Clint value

Fit

Test nominal concentrations in the linear regression fit

AIC

Akaike Information Criterion (AIC) for the linear regression fit

AIC.Null

Akaike Information Criterion of the exponential decay assuming a constant rate of decay

Clint.1

Intrinsic hepatic clearance at 1 uM (frequentist point estimate)

Clint.10

Intrinsic hepatic clearance at 10 uM (frequentist point estimate)

AIC.Sat

Akaike Information Criterion of the exponential decay with a saturation probability

Sat.pValue

p-value of exponential decay with a saturation probability

Source

Wambaugh et al. (2019)

References

Shibata Y, Takahashi H, Chiba M, 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.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.

Wambaugh et al. (2019) Intrinsic Hepatic Clearance Level-4 Data Set

Description

Bayesian estimate of intrinsic hepatic clearance (Clint) measured using in vitro suspensions of pooled primary human hepatocytes (Shibata et al. 2002).

Usage

wambaugh2019.clint.L4

Format

A level-4 data.frame with 473 rows and 12 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Clint.1.Med

Posterior median intrinsic hepatic clearance at 1 uM

Clint.1.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 1 uM (lower credible interval bound)

Clint.1.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 1 uM (upper credible interval bound)

Clint.10.Med

Posterior median intrinsic hepatic clearance at 10 uM

Clint.10.Low

Posterior 2.5th quantile of intrinsic hepatic clearance at 10 uM (lower credible interval bound)

Clint.10.High

Posterior 97.5th quantile of intrinsic hepatic clearance at 10 uM (upper credible interval bound)

Clint.pValue

Probability that a chemical concentration decrease is observed

Sat.pValue

Probability that a lower Clint is observed at a higher concentration, i.e. saturation probability

degrades.pValue

Probability of abiotic degradation

Source

Wambaugh et al. (2019)

References

Shibata Y, Takahashi H, Chiba M, 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.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.

Wambaugh et al. (2019) Rapid Equilibrium Dialysis Level-2 Data Set

Description

Mass spectrometry measurements of plasma protein binding using the rapid equilibrium dialysis (RED) assay method (Waters et al. 2008).

Usage

wambaugh2019.red

Format

A data.frame 15990 rows and 26 variables:

Lab.Sample.Name

Sample description used in the laboratory

Date

Date sample was acquired

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Lab.Compound.Name

Compound as described in the laboratory

Sample.Type

Type of RED sample

Dilution.Factor

Number of times the sample was diluted

Calibration

Identifier for mass spectrometry calibration - usually the date

ISTD.Name

Name of compound used as internal standard (ISTD)

ISTD.Conc

Concentration of ISTD (uM)

ISTD.Area

Peak area internal standard (pixels)

Area

Peak area of analyte (target compound)

Analysis.Method

General description of chemical analysis method

Analysis.Instrument

Instrument(s) used for chemical analysis

Analysis.Parameters

Parameters for identifying analyte peak (for example, retention time)

Note

Any laboratory notes about sample

Level0.File

Name of data file from laboratory that was used to compile level-0 data.frame

Level0.Sheet

Name of "sheet" (for Excel workbooks) from which the laboratory data were read

Time

Time when sample was measured (h)

Test.Compound.Conc

Measured concentration of analytic standard (for calibration curve) (uM)

Test.Nominal.Conc

Expected initial concentration of chemical added to donor side (uM)

Percent.Physiologic.Plasma

Percent of physiology plasma concentration in RED plate (in percent)

Biological.Replicates

Identifier for measurements of multiple samples with the same analyte

Technical.Replicates

Identifier for measurements of one sample of a compound

Response

Response factor (calculated from analyte and ISTD peaks)

Verified

If "Y", then sample is included in the analysis. (Any other value causes the data to be ignored.)

Source

Wambaugh et al. (2019)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.

Wambaugh et al. (2019) Rapid Equilibrium Dialysis Level-3 Data Set

Description

Frequentist estimate of plasma protein binding using the rapid equilibrium dialysis (RED) assay method (Waters et al. 2008).

Usage

wambaugh2019.red.L3

Format

A data.frame 368 rows and 4 variables:

Compound.Name

Compound name

DTXSID

DSSTox Substance Identifier (CompTox Chemicals Dashboard)

Calibration

Identifier for mass spectrometry calibration - usually the date

Fup

Frequentist point estimate for fraction unbound in plasma (fup)

Source

Wambaugh et al. (2019)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.

Wambaugh et al. (2019) Rapid Equilibrium Dialysis Level-4 Data Set

Description

Bayesian estimate of plasma protein binding using the rapid equilibrium dialysis (RED) assay method (Waters et al. 2008).

Usage

wambaugh2019.red.L4

Format

A data.frame 301 rows and 7 variables:

Compound.Name

Compound name

Lab.Compound.Name

Compound as described in the laboratory

DTXSID

DSSTox Substance Identifier (CompTox Chemical Dashboard)

Fup.point

Point estimate of fraction unbound in plasma

Fup.Med

Posterior median fraction unbound in plasma

Fup.Low

Posterior 2.5th quantile of fraction unbound in plasma (lower credible interval bound)

Fup.High

Posterior 97.5th quantile of fraction unbound in plasma (upper credible interval bound)

Source

Wambaugh et al. (2019)

References

Waters NJ, Jones R, Williams G, Sohal B (2008). “Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding.” Journal of pharmaceutical sciences, 97(10), 4586–4595.

Wambaugh JF, Wetmore BA, Ring CL, Nicolas CI, Pearce RG, Honda GS, Dinallo R, Angus D, Gilbert J, Sierra T, others (2019). “Assessing toxicokinetic uncertainty and variability in risk prioritization.” Toxicological Sciences, 172(2), 235–251.