This function solves for the amounts (in umol) or concentrations (in uM) of a chemical in different tissues of a pregnant woman (and her conceptus, i.e., products of conception) as functions of time based on the dose and dosing frequency.
solve_1tri_pbtk(
chem.name = NULL,
chem.cas = NULL,
dtxsid = NULL,
times = seq(0, 13 * 7, 1),
parameters = NULL,
days = NULL,
species = "human",
tsteps = 4,
dose = NULL,
dosing.matrix = NULL,
daily.dose = NULL,
doses.per.day = NULL,
initial.values = NULL,
plots = FALSE,
suppress.messages = FALSE,
iv.dose = FALSE,
input.units = "mg/kg",
output.units = NULL,
physchem.exclude = TRUE,
class.exclude = TRUE,
recalc.blood2plasma = FALSE,
recalc.clearance = FALSE,
adjusted.Funbound.plasma = TRUE,
regression = TRUE,
restrictive.clearance = TRUE,
minimum.Funbound.plasma = 1e-04,
monitor.vars = NULL,
Caco2.options = list(),
atol = 1e-08,
rtol = 1e-08,
...
)A matrix of class deSolve with a column for time(in days), each compartment, the area under the curve, and plasma concentration and a row for each time point.
Either the chemical name, CAS number, or the parameters must be specified.
Either the chemical name, CAS number, or the parameters must be specified.
EPA's DSSTox Structure ID (http://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
Optional time sequence in days. Dosing sequence begins at the beginning of times. Default is from 0th week of pregnancy to 13th due to model representation.
Chemical parameters from parameterize_1tri_pbtk function, overrides chem.name and chem.cas.
Length of the simulation.
Included for compatibility with other functions, but the model will not run for non-human species (default "Human").
The number time steps per hour. Default of 4.
Amount of a single, initial oral dose in mg/kg BW.
A matrix of either one column (or row) with a set of dosing times or with two columns (or rows) correspondingly named "dose" and "time" containing the time and amount, in mg/kg BW, of each dose.
Total daily dose, mg/kg BW.
Number of doses per day.
Vector containing the initial concentrations or amounts of the chemical in specified tissues with units corresponding to compartment.units. Defaults are zero.
Plots all outputs if true.
Whether or not the output message is suppressed.
Simulates a single i.v. dose if true.
Input units of interest assigned to dosing, defaults to mg/kg BW
A named vector of output units expected for the model results. Default, NULL, returns model results in units specified in the 'modelinfo' file. See table below for details.
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).
Exclude chemical classes identified as outside of domain of applicability by relevant modelinfo_[MODEL] file (default TRUE).
Recalculates the ratio of the amount of chemical in the blood to plasma using the input parameters, calculated with hematocrit, Funbound.plasma, and Krbc2pu.
Recalculates the the hepatic clearance (Clmetabolism) with new million.cells.per.gliver parameter.
Uses adjusted Funbound.plasma when set to TRUE along with partition coefficients calculated with this value.
Whether or not to use the regressions in calculating partition coefficients.
Protein binding not taken into account (set to 1) in liver clearance if FALSE.
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).
Which variables to track by default
A list of options to use when working with Caco2 apical
to basolateral data Caco2.Pab, default is Caco2.options =
list(Caco2.Pab.default = 1.6, Caco2.Fabs = TRUE, Caco2.Fgut = TRUE,
overwrite.invivo = FALSE, keepit100 = FALSE). Caco2.Pab.default sets the
default value for Caco2.Pab if Caco2.Pab is unavailable. Caco2.Fabs = TRUE
uses Caco2.Pab to calculate fabs.oral, otherwise fabs.oral = Fabs.
Caco2.Fgut = TRUE uses Caco2.Pab to calculate
fgut.oral, otherwise fgut.oral = Fgut. overwrite.invivo = TRUE
overwrites Fabs and Fgut in vivo values from literature with
Caco2 derived values if available. keepit100 = TRUE overwrites Fabs and Fgut
with 1 (i.e. 100 percent) regardless of other settings.
See get_fbio for further details.
Argument passed to integrator (deSolve).
Argument passed to integrator (deSolve).
Additional arguments passed to the integrator.
Kimberly Truong, John Wambaugh, Mark Sfeir, Dustin Kapraun
The model begins by default at non-pregnancy (0th week) and ends at the 13th week of pregnancy, thereby simulating the 1st trimester. This is meant to augment the fetal_pbtk model (Kapraun et al. 2022) which is limited to the 13th to 40th week window.
Note that the model parameters have units of hours while the model output is in days. Dose is in mg, not scaled for body weight.
Default NULL value for doses.per.day solves for a single dose.
The maternal compartments used in this model are the gut lumen, gut, liver, venous blood, arterial blood, lung, adipose tissue, kidney, thyroid, and rest of body. The "conceptus" compartment models an early developing fetus along with the products of conception (i.e. placenta, amniotic fluid) through which chemical exchange can occur with the maternal blood.
The extra compartments include the amounts or concentrations metabolized by the liver and excreted by the kidneys through the tubules.
AUC is the area under the curve of the plasma concentration.
This gestational model is only parameterized for humans.
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".
truong2025fullpregnancyhttk
solve_model
parameterize_1tri_pbtk
out = solve_1tri_pbtk(chem.name = 'Bisphenol-A', daily.dose = 1,
doses.per.day = 3)
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