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.
chem.physical_and_invitro.dataA data.frame containing 9411 rows and 54 columns.
| Column Name | Description | Units |
| Compound | The preferred name of the chemical compound | none |
| CAS | The preferred Chemical Abstracts Service Registry Number | none |
| CAS.Checksum | A logical indicating whether the CAS number is valid | none |
| DTXSID | DSSTox Structure ID (https://comptox.epa.gov/dashboard) | none |
| Formula | The proportions of atoms within the chemical compound | none |
| All.Compound.Names | All names of the chemical as they occured in the data | none |
| logHenry | The log10 Henry's law constant | log10(atmosphers*m^3/mole) |
| logHenry.Reference | Reference for Henry's law constant | |
| logP | The log10 octanol:water partition coefficient (PC) | log10 unitless ratio |
| logP.Reference | Reference for logPow | |
| logPwa | The log10 water:air PC | log10 unitless ratio |
| logPwa.Reference | Reference for logPwa | |
| logMA | The log10 phospholipid:water PC or "Membrane affinity" | unitless ratio |
| logMA.Reference | Reference for membrane affinity | |
| logWSol | The log10 water solubility | log10(mole/L) |
| logWSol.Reference | Reference for logWsol | |
| MP | The chemical compound melting point | degrees Celsius |
| MP.Reference | Reference for melting point | |
| MW | The chemical compound molecular weight | g/mol |
| MW.Reference | Reference for molecular weight | |
| pKa_Accept | The hydrogen acceptor equilibria concentrations | logarithm |
| pKa_Accept.Reference | Reference for pKa_Accept | |
| pKa_Donor | The hydrogen acceptor equilibria concentrations | logarithm |
| pKa_Donor.Reference | Reference for pKa_Donor | |
| All.Species | All species for which data were available | none |
| DTXSID.Reference | Reference for DTXSID | |
| Formula.Reference | Reference for chemical formulat | |
| [SPECIES].Clint | (Primary hepatocyte suspension) intrinsic hepatic clearance. Entries with comma separated values are Bayesian estimates of the Clint distribution - displayed as the median, 95th credible interval (that is quantile 2.5 and 97.5, respectively), and p-value. | uL/min/10^6 hepatocytes |
| [SPECIES].Clint.pValue | Probability that there is no clearance observed. Values close to 1 indicate clearance is not statistically significant. | none |
| [SPECIES].Clint.pValue.Ref | Reference for Clint pValue | |
| [SPECIES].Clint.Reference | Reference for Clint | |
| [SPECIES].Caco2.Pab | Caco-2 Apical-to-Basal Membrane Permeability | 10^-6 cm/s |
| [SPECIES].Caco2.Pab.Reference | Reference for Caco-2 Membrane Permeability | |
| [SPECIES].Fabs | In vivo measured fraction of an oral dose of chemical absorbed from the gut lumen into the gut | unitless fraction |
| [SPECIES].Fabs.Reference | Reference for Fabs | |
| [SPECIES].Fgut | In vivo measured fraction of an oral dose of chemical that passes gut metabolism and clearance | unitless fraction |
| [SPECIES].Fgut.Reference | Reference for Fgut | |
| [SPECIES].Foral | In vivo measued fractional systemic bioavailability of an oral dose, modeled as he product of Fabs * Fgut * Fhep (where Fhep is first pass hepatic metabolism). | unitless fraction |
| [SPECIES].Foral.Reference | Reference for Foral | |
| [SPECIES].Funbound.plasma | Chemical fraction unbound in presence of plasma proteins (fup). Entries with comma separated values are Bayesian estimates of the fup distribution - displayed as the median and 95th credible interval (that is quantile 2.5 and 97.5, respectively). | unitless fraction |
| [SPECIES].Funbound.plasma.Ref | Reference for Funbound.plasma | |
| [SPECIES].Rblood2plasma | Chemical concentration blood to plasma ratio | unitless ratio |
| [SPECIES].Rblood2plasma.Ref | Reference for Rblood2plasma | |
| Chemical.Class | All classes to which the chemical has been assigned |
John Wambaugh
In some cases the rapid equilbrium dailysis method (Waters et al., 2008) fails to yield detectable concentrations for the free fraction of chemical. In those cases we assume the compound is highly bound (that is, Fup approaches zero). For some calculations (for example, steady-state plasma concentration) there is precendent (Rotroff et al., 2010) for using half the average limit of detection, that is 0.005. We do not recomend using other models where quantities like partition coefficients must be predicted using Fup. We also do not recomend including the value 0.005 in training sets for Fup predictive models.
Note that in some cases the Funbound.plasma and the intrinsic clearance are provided as a series of numbers separated by commas. These values are the result of Bayesian analysis and characterize a distribution: the first value is the median of the distribution, while the second and third values are the lower and upper 95th percentile (that is qunatile 2.5 and 97.5) respectively. For intrinsic clearance a fourth value indicating a p-value for a decrease is provided. Typically 4000 samples were used for the Bayesian analusis, such that a p-value of "0" is equivale to "<0.00025". See Wambaugh et al. (2019) for more details.
Any one chemical compound may have multiple ionization equilibria (see Strope et al., 2018) may both for donating or accepting a proton (and therefore changing charge state). If there are multiple equlibria of the same type (donor/accept])the are concatonated by commas.
All species-specific information is initially from experimental measurements.
The functions load_sipes2017, load_pradeep2020,
and load_dawson2021 may be used to add in silico, structure-based
predictions for many thousands of additional compounds to this table.
CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard)
EPI Suite, https://www.epa.gov/opptintr/exposure/pubs/episuite.htm
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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.
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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.
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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.
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wetmore2015incorporatinghttk
F. L. Wood, J. B. Houston and D. Hallifax 'Drug Metabolism and Disposition November 1, 2017, 45 (11) 1178-1188; DOI: https://doi.org/10.1124/dmd.117.077040
get_physchem_param
get_invitroPK_param
add_chemtable