httk (version 1.9.2)

calc_mc_oral_equiv: Calculate Monte Carlo Oral Equivalent Dose

Description

This functions converts a chemical plasma concetration to an oral equivalent dose using a concentration obtained from calc_mc_css.

Usage

calc_mc_oral_equiv(conc,chem.name=NULL,
                   chem.cas=NULL,
                   which.quantile=0.95,
                   species="Human",
                   input.units='uM',
                   output.units='mg',
                   suppress.messages=F,
                   return.samples=F,
                   restrictive.clearance=T,
                   plasma.binding = F, 
                   tk.statistic.used="mean", 
                   tissue=NULL,
                   IVIVE = NULL,
                   ...)

Arguments

conc

Bioactive in vitro concentration in units of uM.

chem.name

Either the chemical name or the CAS number must be specified.

chem.cas

Either the CAS number or the chemical name must be specified.

suppress.messages

Suppress text messages.

input.units

Units of given concentration, default of uM but can also be mg/L.

output.units

Units of dose, default of 'mg' for mg/kg BW/ day or 'mol' for mol/ kg BW/ day.

which.quantile

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

Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or default "Human").

return.samples

Whether or not to return the vector containing the samples from the simulation instead of the selected quantile.

restrictive.clearance

Protein binding not taken into account (set to 1) in liver clearance if FALSE.

plasma.binding

If TRUE, then only the free (unbound) fraction of chemical is considered to be bioactive. If FALSE, the total chemical concentration is used for IVIVE. (Default TRUE)

tk.statistic.used

Theoreticially either the "mean" or "max"imum (peak) concetrations might be used for IVIVE with some models. Defaults to "mean". Meaningless for the steady-state model (Argument is currently ignored because analytic steady-state solutions are used by this function.).

tissue

Desired steady state tissue conentration.

IVIVE

Honda et al. (submitted) 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.

Value

Equivalent dose in specified units, default of mg/kg BW/day.

Details

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 substitues 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 extrpolation (IVIVE) assumptions identified by Honda et al. (submitted) 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.

Examples

# NOT RUN {
# }
# NOT RUN {
calc_mc_oral_equiv(0.1,chem.cas="34256-82-1",which.quantile=c(0.05,0.5,0.95),
                   method='vi',samples=100,tissue='brain')
# }