get_fbio

This function checks for chemical-specific in vivo measurements of the 
fraction absorbed from the
gut in the <code>chem.physical_and_invitro.data</code> table. If in vivo
data are unavailable (or <code>keepit100 == TRUE</code>) we attempt to use 
in vitro Caco-2 membrane permeability to predict the fractions according to
<code>calc_fbio.oral</code>.

Parameter

oral_bioavailability

Pre-made models that can be rapidly tailored to various chemicals
and species using chemical-specific in vitro data and physiological
information. These tools allow incorporation of chemical
toxicokinetics ("TK") and in vitro-in vivo extrapolation ("IVIVE")
into bioinformatics, as described by Pearce et al. (2017)
(<doi:10.18637/jss.v079.i04>). Chemical-specific
in vitro data characterizing toxicokinetics have been obtained
from relatively high-throughput experiments. The
chemical-independent ("generic") physiologically-based ("PBTK") and empirical
(for example, one compartment) "TK" models included here can be
parameterized with in vitro data or in silico predictions which are
provided for thousands of chemicals, multiple exposure routes,
and various species. High throughput toxicokinetics ("HTTK") is the
combination of in vitro data and generic models. We establish the
expected accuracy of HTTK for chemicals without in vivo data
through statistical evaluation of HTTK predictions for chemicals
where in vivo data do exist. The models are systems of ordinary
differential equations that are developed in MCSim and solved
using compiled (C-based) code for speed. A Monte Carlo sampler is
included for simulating human biological variability
(Ring et al., 2017 <doi:10.1016/j.envint.2017.06.004>)
and propagating parameter uncertainty
(Wambaugh et al., 2019 <doi:10.1093/toxsci/kfz205>).
Empirically calibrated methods are included for predicting
tissue:plasma partition coefficients and volume of distribution
(Pearce et al., 2017 <doi:10.1007/s10928-017-9548-7>).
These functions and data provide a set of tools for using IVIVE to
convert concentrations from high-throughput screening experiments
(for example, Tox21, ToxCast) to real-world exposures via reverse
dosimetry (also known as "RTK")
(Wetmore et al., 2015 <doi:10.1093/toxsci/kfv171>).

John Wambaugh

httk

High-Throughput Toxicokinetics

Sarah Davidson-Fritz

Robert Pearce

Caroline Ring

Greg Honda

Mark Sfeir

Matt Linakis

Dustin Kapraun

Nathan Pollesch

Miyuki Breen

Shannon Bell

Xiaoqing Chang

Todor Antonijevic

Jimena Davis

Elaina Kenyon

Katie Paul Friedman

Celia Schacht

Meredith Scherer

James Sluka

Noelle Sinski

Nisha Sipes

Barbara Wetmore

Lily Whipple

Woodrow Setzer

get_fbio function

<dl><dt>parameters</dt>
<dd>A list of the parameters (Caco2.Pab, Funbound.Plasma, Rblood2plasma,
Clint, BW, Qsmallintestine, Fabs, Fgut) used in the calculation, either supplied by user
or calculated in parameterize_steady_state.</dd>
<dt>chem.cas</dt>
<dd>Chemical Abstract Services Registry Number (CAS-RN) -- the 
chemical must be identified by either CAS, name, or DTXISD</dd>
<dt>chem.name</dt>
<dd>Chemical name (spaces and capitalization ignored) -- the 
chemical must be identified by either CAS, name, or DTXISD</dd>
<dt>dtxsid</dt>
<dd>EPA's DSSTox Structure ID (<a href="https://comptox.epa.gov/dashboard">https://comptox.epa.gov/dashboard</a>)
-- the chemical must be identified by either CAS, name, or DTXSIDs</dd>
<dt>species</dt>
<dd>Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or
default "Human").</dd>
<dt>default.to.human</dt>
<dd>Substitutes missing rat values with human values if
true.</dd>
<dt>Caco2.Pab.default</dt>
<dd>sets the default value for Caco2.Pab if Caco2.Pab is 
unavailable.</dd>
<dt>Caco2.Fgut</dt>
<dd>= TRUE uses Caco2.Pab to calculate fgut.oral, otherwise 
fgut.oral = <code>Fgut</code>.</dd>
<dt>Caco2.Fabs</dt>
<dd>= TRUE uses Caco2.Pab to calculate
fabs.oral, otherwise fabs.oral = <code>Fabs</code>.</dd>
<dt>overwrite.invivo</dt>
<dd>= TRUE overwrites Fabs and Fgut in vivo values from 
literature with Caco2 derived values if available.</dd>
<dt>keepit100</dt>
<dd>TRUE overwrites Fabs and Fgut with 1 (i.e. 100 percent) 
regardless of other settings.</dd>
<dt>suppress.messages</dt>
<dd>Whether or not the output message is suppressed.</dd></dl>

Arguments

Author

Retrieve or calculate fraction of chemical absorbed from the gut — get_fbio

<dl>

<dt>parameters</dt>
<dd>A list of the parameters (Caco2.Pab, Funbound.Plasma, Rblood2plasma,
Clint, BW, Qsmallintestine, Fabs, Fgut) used in the calculation, either supplied by user
or calculated in parameterize_steady_state.</dd>


<dt>chem.cas</dt>
<dd>Chemical Abstract Services Registry Number (CAS-RN) -- the 
chemical must be identified by either CAS, name, or DTXISD</dd>


<dt>chem.name</dt>
<dd>Chemical name (spaces and capitalization ignored) -- the 
chemical must be identified by either CAS, name, or DTXISD</dd>


<dt>dtxsid</dt>
<dd>EPA's DSSTox Structure ID (<a href='https://comptox.epa.gov/dashboard'>https://comptox.epa.gov/dashboard</a>)
-- the chemical must be identified by either CAS, name, or DTXSIDs</dd>


<dt>species</dt>
<dd>Species desired (either "Rat", "Rabbit", "Dog", "Mouse", or
default "Human").</dd>


<dt>default.to.human</dt>
<dd>Substitutes missing rat values with human values if
true.</dd>


<dt>Caco2.Pab.default</dt>
<dd>sets the default value for Caco2.Pab if Caco2.Pab is 
unavailable.</dd>


<dt>Caco2.Fgut</dt>
<dd>= TRUE uses Caco2.Pab to calculate fgut.oral, otherwise 
fgut.oral = <code>Fgut</code>.</dd>


<dt>Caco2.Fabs</dt>
<dd>= TRUE uses Caco2.Pab to calculate
fabs.oral, otherwise fabs.oral = <code>Fabs</code>.</dd>


<dt>overwrite.invivo</dt>
<dd>= TRUE overwrites Fabs and Fgut in vivo values from 
literature with Caco2 derived values if available.</dd>


<dt>keepit100</dt>
<dd>TRUE overwrites Fabs and Fgut with 1 (i.e. 100 percent) 
regardless of other settings.</dd>


<dt>suppress.messages</dt>
<dd>Whether or not the output message is suppressed.</dd>

</dl>

Retrieve or calculate fraction of chemical absorbed from the gut

get_fbio: Retrieve or calculate fraction of chemical absorbed from the gut

Description

Usage

Arguments

Author