parameterize_3comp2 {httk} | R Documentation |
Parameters for a three-compartment toxicokinetic model (dynamic)
Description
This function generates the chemical- and species-specific parameters needed
for model '3compartment', for example solve_3comp
. A call is
masde to parameterize_pbtk
to use Schmitt (2008)'s method
as modified by Pearce et al. (2017) to predict partition coefficients based
on descriptions in tissue.data
. Organ volumes and flows are
retrieved from table physiology.data
.
Usage
parameterize_3comp2(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
default.to.human = FALSE,
physchem.exclude = TRUE,
class.exclude = TRUE,
force.human.clint.fup = FALSE,
clint.pvalue.threshold = 0.05,
adjusted.Funbound.plasma = TRUE,
adjusted.Clint = TRUE,
regression = TRUE,
suppress.messages = FALSE,
restrictive.clearance = TRUE,
minimum.Funbound.plasma = 1e-04,
Caco2.options = NULL,
...
)
Arguments
chem.cas |
Chemical Abstract Services Registry Number (CAS-RN) – the chemical must be identified by either CAS, name, or DTXISD |
chem.name |
Chemical name (spaces and capitalization ignored) – the chemical must be identified by either CAS, name, or DTXISD |
dtxsid |
EPA's 'DSSTox Structure ID (https://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"). |
default.to.human |
Substitutes missing animal values with human values if true. |
physchem.exclude |
Exclude chemicals on the basis of physico-chemical properties (currently only Henry's law constant) as specified by the relevant modelinfo_[MODEL] file (default TRUE). |
class.exclude |
Exclude chemical classes identified as outside of domain of applicability by relevant modelinfo_[MODEL] file (default TRUE). |
force.human.clint.fup |
Forces use of human values for hepatic intrinsic clearance and fraction of unbound plasma if true. |
clint.pvalue.threshold |
Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero. |
adjusted.Funbound.plasma |
Uses Pearce et al. (2017) lipid binding adjustment for Funbound.plasma (which impacts partition coefficients) when set to TRUE (Default). |
adjusted.Clint |
Uses Kilford et al. (2008) hepatocyte incubation binding adjustment for Clint when set to TRUE (Default). |
regression |
Whether or not to use the regressions in calculating partition coefficients. |
suppress.messages |
Whether or not the output message is suppressed. |
restrictive.clearance |
In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE. |
minimum.Funbound.plasma |
Monte Carlo draws less than this value are set equal to this value (default is 0.0001 – half the lowest measured Fup in our dataset). |
Caco2.options |
A list of options to use when working with Caco2 apical
to basolateral data |
... |
Additional arguments are passed to |
Details
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
BW |
Body Weight, 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. |
Kgut2pu |
Ratio of concentration of chemical in gut tissue to unbound concentration in plasma. |
Kliver2pu |
Ratio of concentration of chemical in liver 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. |
million.cells.per.gliver |
Millions cells per gram of liver tissue. |
MW |
Molecular Weight, g/mol. |
Qcardiacc |
Cardiac Output, L/h/kg BW^3/4. |
Qgfrc |
Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted. |
Qgutf |
Fraction of cardiac output flowing to the gut. |
Qliverf |
Fraction of cardiac output flowing to the liver. |
Rblood2plasma |
The ratio of the concentration of the chemical in the blood to the concentration in the plasma. |
Vgutc |
Volume of the gut per kg body weight, L/kg BW. |
Vliverc |
Volume of the liver per kg body weight, L/kg BW. |
Vrestc |
Volume of the rest of the body per kg body weight, L/kg BW. |
Author(s)
John Wambaugh
References
Pearce RG, Setzer RW, Strope CL, Wambaugh JF, Sipes NS (2017). “Httk: R package for high-throughput toxicokinetics.” Journal of Statistical Software, 79(4), 1. doi:10.18637/jss.v079.i04.
Schmitt W (2008). “General approach for the calculation of tissue to plasma partition coefficients.” Toxicology in vitro, 22(2), 457–467. doi:10.1016/j.tiv.2007.09.010.
Pearce RG, Setzer RW, Davis JL, Wambaugh JF (2017). “Evaluation and calibration of high-throughput predictions of chemical distribution to tissues.” Journal of pharmacokinetics and pharmacodynamics, 44, 549–565. doi:10.1007/s10928-017-9548-7.
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.
Wambaugh JF, Schacht CM, Ring CL (2025). “A Simple Physiologically Based Toxicokinetic Model for Multi-Route In Vitro–In Vivo Extrapolation.” Environmental Science & Technology Letters, 12(3), 261–268. doi:10.1021/acs.estlett.4c00967.
See Also
Examples
parameters <- parameterize_3comp2(chem.name='Bisphenol-A',species='Rat')
parameters <- parameterize_3comp2(chem.cas='80-05-7',
species='rabbit',default.to.human=TRUE)
out <- solve_3comp2(parameters=parameters,plots=TRUE)