calc_hep_fu

This function uses the method from Kilford et al. (2008) to calculate the
fraction of unbound chemical in the 
 hepatocyte intrinsic clearance assay. The bound chemical is presumed to be
unavailable during the performance of the assay, so this fraction can be
used to increase the apparent clearance rate to better estimate in vivo 
clearance. 
For bases, the fraction of chemical unbound in hepatocyte clearance assays 
(fuhep) is calculated in terms of 
logPow
but for neutrual and acidic compounds we use 
logDow (from <code>calc_dow</code>). 
Here we denote the appropriate partition coefficient as "logP/D".
Kilford et al. (2008) calculates
fuhep = 1/(1 + 125*VR*10^(0.072*logP/D2 + 0.067*logP/D-1.126))

in-vitro

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

calc_hep_fu function

<dl><dt>chem.cas</dt>
<dd>Chemical Abstract Services Registry Number (CAS-RN) -- if
parameters is not specified then the chemical must be identified by either
CAS, name, or DTXISD</dd>
<dt>chem.name</dt>
<dd>Chemical name (spaces and capitalization ignored) -- if
parameters is not specified then 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>)
 -- if parameters is not specified then the chemical must be identified by 
either CAS, name, or DTXSIDs</dd>
<dt>parameters</dt>
<dd>Parameters from the appropriate parameterization function
for the model indicated by argument model</dd>
<dt>Vr</dt>
<dd>Ratio of cell volume to incubation volume. Default (0.005) is taken from</dd>
<dt>pH</dt>
<dd>pH of the incupation medium.</dd></dl>

Arguments

Author

Calculate the free chemical in the hepaitic clearance assay — calc_hep_fu

<dl>

<dt>chem.cas</dt>
<dd>Chemical Abstract Services Registry Number (CAS-RN) -- if
parameters is not specified then the chemical must be identified by either
CAS, name, or DTXISD</dd>


<dt>chem.name</dt>
<dd>Chemical name (spaces and capitalization ignored) -- if
parameters is not specified then 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>)
 -- if parameters is not specified then the chemical must be identified by 
either CAS, name, or DTXSIDs</dd>


<dt>parameters</dt>
<dd>Parameters from the appropriate parameterization function
for the model indicated by argument model</dd>


<dt>Vr</dt>
<dd>Ratio of cell volume to incubation volume. Default (0.005) is taken from</dd>


<dt>pH</dt>
<dd>pH of the incupation medium.</dd>

</dl>

Calculate the free chemical in the hepaitic clearance assay

calc_hep_fu: Calculate the free chemical in the hepaitic clearance assay

Description

Usage

Value

Arguments

Author

Details

References

See Also