This functions converts a chemical plasma concetration to an oral equivalent
dose using a concentration obtained from calc_mc_css.
calc_mc_oral_equiv(
conc,
chem.name = NULL,
chem.cas = NULL,
dtxsid = NULL,
which.quantile = 0.95,
species = "Human",
input.units = "uM",
output.units = "mgpkgpday",
suppress.messages = FALSE,
return.samples = FALSE,
concentration = "plasma",
restrictive.clearance = TRUE,
bioactive.free.invivo = FALSE,
tissue = NULL,
IVIVE = NULL,
...
)Equivalent dose in specified units, default of mg/kg BW/day.
Bioactive in vitro concentration in units of uM.
Either the chemical name or the CAS number must be specified.
Either the CAS number or the chemical name must be specified.
EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard) the chemical must be identified by either CAS, name, or DTXSIDs
Which quantile from Monte Carlo steady-state
simulation (calc_mc_css) is requested. Can be a vector. Note that 95th
concentration quantile is the same population as the 5th dose quantile.
Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").
Units of given concentration, default of uM but can also be mg/L.
Units of dose, default of 'mgpkgpday' for mg/kg BW/ day or 'umolpkgpday' for umol/ kg BW/ day.
Suppress text messages.
Whether or not to return the vector containing the samples from the simulation instead of the selected quantile.
Desired concentration type, 'blood','tissue', or default 'plasma'.
Protein binding not taken into account (set to 1) in liver clearance if FALSE.
If FALSE (default), then the total concentration is treated as bioactive in vivo. If TRUE, the the unbound (free) plasma concentration is treated as bioactive in vivo. Only works with tissue = NULL in current implementation.
Desired steady state tissue conentration.
Honda et al. (2019) identified six plausible sets of assumptions for in vitro-in vivo extrapolation (IVIVE) assumptions. Argument may be set to "Honda1" through "Honda6". If used, this function overwrites the tissue, restrictive.clearance, and plasma.binding arguments. See Details below for more information.
Additional parameters passed to calc_mc_css for httkpop and
variance of parameters.
John Wambaugh
All arguments after httkpop only apply if httkpop is set to TRUE and species to "Human".
When species is specified as rabbit, dog, or mouse, the function uses the appropriate physiological data(volumes and flows) but substitutes human fraction unbound, partition coefficients, and intrinsic hepatic clearance.
Tissue concentrations are calculated for the pbtk model with oral infusion dosing. All tissues other than gut, liver, and lung are the product of the steady state plasma concentration and the tissue to plasma partition coefficient.
The six sets of plausible in vitro-in vivo extrapolation (IVIVE) assumptions identified by Honda et al. (2019) are:
| in vivo Conc. | Metabolic Clearance | Bioactive Chemical Conc. | TK Statistic Used* | |
| Honda1 | Veinous (Plasma) | Restrictive | Free | Mean Conc. |
| Honda2 | Veinous | Restrictive | Free | Max Conc. |
| Honda3 | Veinous | Non-restrictive | Total | Mean Conc. |
| Honda4 | Veinous | Non-restrictive | Total | Max Conc. |
| Honda5 | Target Tissue | Non-restrictive | Total | Mean Conc. |
| Honda6 | Target Tissue | Non-restrictive | Total | Max Conc. |
*Assumption is currently ignored because analytical steady-state solutions are currently used by this function.
Wetmore, Barbara A., et al. "Incorporating high-throughput exposure predictions with dosimetry-adjusted in vitro bioactivity to inform chemical toxicity testing." Toxicological Sciences 148.1 (2015): 121-136.
Ring, Caroline L., et al. "Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability." Environment international 106 (2017): 105-118.
Honda, Gregory S., et al. "Using the Concordance of In Vitro and In Vivo Data to Evaluate Extrapolation Assumptions." 2019. PLoS ONE 14(5): e0217564.
Rowland, Malcolm, Leslie Z. Benet, and Garry G. Graham. "Clearance concepts in pharmacokinetics." Journal of pharmacokinetics and biopharmaceutics 1.2 (1973): 123-136.
# \donttest{
calc_mc_oral_equiv(0.1,chem.cas="34256-82-1",which.quantile=c(0.05,0.5,0.95),
tissue='brain')
# }
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