calc_dow

This function estimates the ratio of the equilibrium concentrations of
a compound in octanol and water, taking into account the charge of the
compound. Given the pH, we assume the neutral (uncharged) fraction of
compound partitions according to the hydrophobicity 
(Pow). We assume that
only a fraction alpha (defaults to 0.001 -- Schmitt (2008)) of the charged
compound partitions into lipid (octanol):
Dow = Pow*(Fneutral + alpha*Fcharged)
Fractions charged are calculated
according to hydrogen ionization equilibria (pKa_Donor, pKa_Accept) using
<code>calc_ionization</code>.

Parameter

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

Kimberly Truong

Colin Thomson

Miyuki Breen

Shannon Bell

Xiaoqing Chang

Todor Antonijevic

Jimena Davis

Elaina Kenyon

Gilberto Padilla Mercado

Katie Paul Friedman

Nathan Pollesch

Celia Schacht

Meredith Scherer

James Sluka

Noelle Sinski

Nisha Sipes

Barbara Wetmore

Lily Whipple

Woodrow Setzer

calc_dow function

<dl><dt>Pow</dt>
<dd>Octanol:water partition coefficient (ratio of concentrations)</dd>
<dt>chem.cas</dt>
<dd>Either the chemical name or the CAS number must be
specified.</dd>
<dt>chem.name</dt>
<dd>Either the chemical name or the CAS number must be
specified.</dd>
<dt>dtxsid</dt>
<dd>EPA's 'DSSTox Structure ID (https://comptox.epa.gov/dashboard)
the chemical must be identified by either CAS, name, or DTXSIDs</dd>
<dt>parameters</dt>
<dd>Chemical parameters from a parameterize_MODEL function,
overrides chem.name and chem.cas.</dd>
<dt>pH</dt>
<dd>pH where ionization is evaluated.</dd>
<dt>pKa_Donor</dt>
<dd>Compound H dissociation equilibirum constant(s).
Overwrites chem.name and chem.cas.</dd>
<dt>pKa_Accept</dt>
<dd>Compound H association equilibirum constant(s).
Overwrites chem.name and chem.cas.</dd>
<dt>fraction_charged</dt>
<dd>Fraction of chemical charged at the given pH</dd>
<dt>alpha</dt>
<dd>Ratio of Distribution coefficient D of totally charged species and that of the neutral form</dd></dl>

Arguments

Author

Calculate the distribution coefficient — calc_dow

<dl>

<dt>Pow</dt>
<dd>Octanol:water partition coefficient (ratio of concentrations)</dd>


<dt>chem.cas</dt>
<dd>Either the chemical name or the CAS number must be
specified.</dd>


<dt>chem.name</dt>
<dd>Either the chemical name or the CAS number must be
specified.</dd>


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


<dt>parameters</dt>
<dd>Chemical parameters from a parameterize_MODEL function,
overrides chem.name and chem.cas.</dd>


<dt>pH</dt>
<dd>pH where ionization is evaluated.</dd>


<dt>pKa_Donor</dt>
<dd>Compound H dissociation equilibirum constant(s).
Overwrites chem.name and chem.cas.</dd>


<dt>pKa_Accept</dt>
<dd>Compound H association equilibirum constant(s).
Overwrites chem.name and chem.cas.</dd>


<dt>fraction_charged</dt>
<dd>Fraction of chemical charged at the given pH</dd>


<dt>alpha</dt>
<dd>Ratio of Distribution coefficient D of totally charged species and that of the neutral form</dd>

</dl>

Calculate the distribution coefficient

calc_dow: Calculate the distribution coefficient

Description

Usage

Value

Arguments

Author

References

See Also