parameterize_1tri_pbtk {httk} | R Documentation |
Parameterize_1tri_PBTK
Description
This function initializes the parameters needed in the functions solve_1tri_pbtk by calling parameterize_pbtk and adding additional parameters.
Usage
parameterize_1tri_pbtk(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
return.kapraun2019 = TRUE,
suppress.messages = FALSE,
...
)
Arguments
chem.cas |
Either the chemical name or the CAS number must be specified. |
chem.name |
Either the chemical name or the CAS number must be specified. |
dtxsid |
EPA's DSSTox Structure ID (http://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs |
species |
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human"). Currently only a human model is supported. |
return.kapraun2019 |
If TRUE (default), empirical parameters from Kapraun et al. (2019) necessary for defining the model are provided. This is a subset of the httk::kapraun2019 list object with additional parameters. |
suppress.messages |
Whether or not the output message is suppressed. |
... |
Arguments passed to parameterize_pbtk. |
Details
Because this model does not simulate exhalation, inhalation, and other processes relevant to volatile chemicals, this model is by default restricted to chemicals with a logHenry's Law Constant less than that of Acetone, a known volatile chemical. That is, chemicals with logHLC > -4.5 (Log10 atm-m3/mole) are excluded. Volatility is not purely determined by the Henry's Law Constant, therefore this chemical exclusion may be turned off with the argument "physchem.exclude = FALSE". Similarly, per- and polyfluoroalkyl substances (PFAS) are excluded by default because the transporters that often drive PFAS toxicokinetics are not included in this model. However, PFAS chemicals can be included with the argument "class.exclude = FALSE".
Value
pre_pregnant_BW |
Body Weight before pregnancy, kg. |
Clmetabolismc |
Hepatic Clearance, L/h/kg BW. |
Fabsgut |
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen. |
Funbound.plasma |
Fraction of plasma that is not bound. |
Fhep.assay.correction |
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008) |
hematocrit |
Percent volume of red blood cells in the blood. |
Kadipose2pu |
Ratio of concentration of chemical in adipose tissue to unbound concentration in plasma. |
Kconceptus2pu_initial |
Ratio of concentration of chemical in "conceptus" compartment to unbound concentration in plasma at time 0. |
Kconceptus2pu_final |
Ratio of concentration of chemical in "conceptus" compartment to unbound concentration in plasma at 13 weeks. |
Kgut2pu |
Ratio of concentration of chemical in gut tissue to unbound concentration in plasma. |
kgutabs |
Rate that chemical enters the gut from gutlumen, 1/h. |
Kkidney2pu |
Ratio of concentration of chemical in kidney tissue to unbound concentration in plasma. |
Kliver2pu |
Ratio of concentration of chemical in liver tissue to unbound concentration in plasma. |
Klung2pu |
Ratio of concentration of chemical in lung tissue to unbound concentration in plasma. |
Krbc2pu |
Ratio of concentration of chemical in red blood cells to unbound concentration in plasma. |
Krest2pu |
Ratio of concentration of chemical in rest of body tissue to unbound concentration in plasma. |
Kthyroid2pu |
Ratio of concentration of chemical in thyroid tissue to unbound concentration in plasma. |
million.cells.per.gliver |
Millions cells per gram of liver tissue. |
MW |
Molecular Weight, g/mol. |
pH_Plasma_mat |
pH of the maternal plasma. |
Qgfr |
Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted. |
Vgutc |
Volume of the gut per kg body weight, L/kg BW. |
Vkidneyc |
Volume of the kidneys per kg body weight, L/kg BW. |
Vliverc |
Volume of the liver per kg body weight, L/kg BW. |
Vlungc |
Volume of the lungs per kg body weight, L/kg BW. |
Vthyroidc |
Volume of the thyroid per kg body weight, L/kg BW. |
Author(s)
Kimberly Truong, Mark Sfeir, Dustin Kapraun, John Wambaugh
References
Kilford PJ, Gertz M, Houston JB, Galetin A (2008). “Hepatocellular binding of drugs: correction for unbound fraction in hepatocyte incubations using microsomal binding or drug lipophilicity data.” Drug Metabolism and Disposition, 36(7), 1194–1197. doi:10.1124/dmd.108.020834.
Kapraun DF, Wambaugh JF, Setzer RW, Judson RS (2019). “Empirical models for anatomical and physiological changes in a human mother and fetus during pregnancy and gestation.” PLOS ONE, 14(5), 1-56. doi:10.1371/journal.pone.0215906.
Kapraun DF, Sfeir M, Pearce RG, Davidson-Fritz SE, Lumen A, Dallmann A, Judson RS, Wambaugh JF (2022). “Evaluation of a rapid, generic human gestational dose model.” Reproductive Toxicology, 113, 172–188. doi:10.1016/j.reprotox.2022.09.004.
Truong KT, Wambaugh JF, Kapraun DF, Davidson-Fritz SE, Eytcheson S, Judson RS, Paul Friedman K (2025). “Interpretation of thyroid-relevant bioactivity data for comparison to in vivo exposures: A prioritization approach for putative chemical inhibitors of in vitro deiodinase activity.” Toxicology. doi:10.1016/j.tox.2025.154157.
See Also
Examples
parameters <- parameterize_1tri_pbtk(dtxsid = "DTXSID7020182")
parameters <- parameterize_1tri_pbtk(chem.name='Bisphenol-A')