This function initializes the parameters needed in the functions calc_mc_css, calc_mc_oral_equiv, and calc_analytic_css for the three compartment steady state model ('3compartmentss').
parameterize_steadystate(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
clint.pvalue.threshold = 0.05,
default.to.human = FALSE,
human.clint.fup = FALSE,
adjusted.Funbound.plasma = TRUE,
restrictive.clearance = TRUE,
fup.lod.default = 0.005,
suppress.messages = FALSE,
minimum.Funbound.plasma = 1e-04
)Hepatic Intrinsic Clearance, uL/min/10^6 cells.
Fraction of the oral dose absorbed, i.e. the fraction of the dose that enters the gutlumen.
Fraction of plasma that is not bound.
Flow rate of blood exiting the liver, L/h/kg BW^3/4.
Glomerular Filtration Rate, L/h/kg BW^3/4, volume of fluid filtered from kidney and excreted.
Body Weight, kg
Molecular Weight, g/mol
Millions cells per gram of liver tissue.
Volume of the liver per kg body weight, L/kg BW.
Liver tissue density, kg/L.
The fraction of chemical unbound in hepatocyte assay using the method of Kilford et al. (2008)
Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model.
Chemical Abstract Services Registry Number (CAS-RN) -- the chemical must be identified by either CAS, name, or DTXISD
Chemical name (spaces and capitalization ignored) -- the chemical must be identified by either CAS, name, or DTXISD
EPA's DSSTox Structure ID (https://comptox.epa.gov/dashboard) -- the chemical must be identified by either CAS, name, or DTXSIDs
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Hepatic clearances with clearance assays having p-values greater than the threshold are set to zero.
Substitutes missing rat values with human values if true.
Uses human hepatic intrinsic clearance and fraction of unbound plasma in calculation of partition coefficients for rats if true.
Returns adjusted Funbound.plasma when set to TRUE.
In calculating hepatic.bioavailability, protein binding is not taken into account (set to 1) in liver clearance if FALSE.
Default value used for fraction of unbound plasma for chemicals where measured value was below the limit of detection. Default value is 0.0005.
Whether or not the output message is suppressed.
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).
John Wambaugh
Pearce, Robert G., et al. "Httk: R package for high-throughput toxicokinetics." Journal of statistical software 79.4 (2017): 1.
Kilford, P. J., Gertz, M., Houston, J. B. and 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), 1194-7, 10.1124/dmd.108.020834.
parameters <- parameterize_steadystate(chem.name='Bisphenol-A',species='Rat')
parameters <- parameterize_steadystate(chem.cas='80-05-7')
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