This function initializes the parameters needed in the function solve_1comp. The toxiokinetic model is of the form of an empirical, single compartment in which all tissues are well mixed. The route of exposure can be oral or intravenous. For oral exposures a hepatic extraction factor (first-pass metabolism) is estimated using chemical-specific in vitro-measured intrinsic hepatic clearance and fraction unbound in plasma, if available. If these chemical-specific parameters are not available then all chemical is assumed to be absorbed. The rate of oral absorption used is 2.2 L/h, the median rate observed across 44 chemicals by Wambaugh et al. (2018) (tools:::Rd_expr_doi("10.1093/toxsci/kfy020")). There is a single, unspecified route of elimination (clearance). Half-life is estimated using the Dawson et al. (2023) (tools:::Rd_expr_doi("10.3390/toxics11020098")) machine learning model for per- and poly-flurinated alkyl substances (PFAS). In keeping with the findings of that paper, volume of distribtuion is held fixed at 0.205 L kg/BW. Clearance is calculated as the product of elimination rate (determined from half-life) and the volume of distribution. The ratio of chemical concentration in blood to plasma is determined according to Poothong et al. (2017) (tools:::Rd_expr_doi("10.1021/acs.est.7b03299")) where compounds that are ionized at pH 7.4 (plasma) get a value of 0.5, while chemicals that are neutral get a value of 20.
parameterize_pfas1comp(
chem.cas = NULL,
chem.name = NULL,
dtxsid = NULL,
species = "Human",
sex = "Female",
dosingadj = "Oral",
restrict.doa = "ClassModDomain",
estimate.firstpass = TRUE,
suppress.messages = FALSE,
Caco2.options = list(),
class.exclude = TRUE,
physchem.exclude = TRUE
)Volume of distribution, units of L/kg BW.
Volume of the plasma, L/kg BW.
Fraction of the oral dose absorbed, that is, the fraction of the dose that enters the gutlumen.
Not used for this model
Elimination rate, units of 1/h.
Percent volume of red blood cells in the blood.
Rate chemical is absorbed, 1/h.
Not used for this model
Molecular Weight, g/mol.
The ratio of the concentration of the chemical in the blood to the concentration in the plasma. Not used in calculations but included for the conversion of plasma outputs.
Fraction of dose remaining after first pass clearance, calculated from the corrected well-stirred model.
Body Weight, kg.
Ionization equilibria (if any) for hydrogen donation (acids).
Ionization equilibria (if any) for hydrogen acceptance (bases).
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").
Sex of simulated individual ("Male" or "Female")
Route of dosing for Dawson et al. (2023) PFAS half-life model ("oral", "iv", or "other")
Whether to restrict to chemicals within an estimated domain of applicability based on the properties of the training set ("ClassModDomain"), the domain of all models ("AMAD"), or none ("none") (Defaults to "ClassModDomain").
Whether to estimate first-pass hepatic metabolism, which can only be done for a subset of PFAS with in vitro HTTK parameters (Defaults to TRUE).
Whether to suppress messages (Defaults to FALSE).
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.
Exclude chemical classes identified as outside of domain of applicability by relevant modelinfo_[MODEL] file (default TRUE).
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).
John Wambaugh
Dawson, Daniel E., et al. "A Machine Learning Model to Estimate Toxicokinetic Half-Lives of Per-and Polyfluoro-Alkyl Substances (PFAS) in Multiple Species." Toxics 11.2 (2023): 98.
pearce2017httkhttk
schmitt2008generalhttk
pearce2017evaluationhttk
Wambaugh, John F., et al. "Evaluating in vitro-in vivo extrapolation of toxicokinetics." Toxicological Sciences 163.1 (2018): 152-169.
Poothong, Somrutai, et al. "Distribution of novel and well-known poly-and perfluoroalkyl substances (PFASs) in human serum, plasma, and whole blood." Environmental Science & Technology 51.22 (2017): 13388-13396.
solve_1comp
calc_analytic_css_1comp
calc_vdist
parameterize_steadystate
apply_clint_adjustment
tissue.data
physiology.data
# Human elimination rate for PFOA:
parameterize_pfas1comp(dtxsid="DTXSID8031865")$kelim
# Female rat is much faster than human:
parameterize_pfas1comp(dtxsid="DTXSID8031865", species="rat")$kelim
# Male rat is slower than female but faster than humans:
parameterize_pfas1comp(dtxsid="DTXSID8031865", species="rat", sex="male")$kelim
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