parameterize_IVD

This function collects physicochemical properties from chemicals input by the user for use with armitage.R and kramer.R.

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

Meredith Scherer

Annabel Meade

Celia Schacht

Todor Antonijevic

Miyuki Breen

Shannon Bell

Xiaoqing Chang

Jimena Davis

Elaina Kenyon

Gilberto Padilla Mercado

Katie Paul Friedman

Nathan Pollesch

Noelle Sinski

Nisha Sipes

James Sluka

Caroline Stevens

Barbara Wetmore

Lily Whipple

Woodrow Setzer

parameterize_IVD function

<dl><dt>tcdata</dt>
<dd>A data.table with casrn, nomconc, MP, gkow, gkaw, gswat, sarea,
v_total, v_working. Otherwise supply single values to this.params (e.g., this.sarea,
this.v_total, etc.). Chemical parameters are taken from 
<code>chem.physical_and_invitro.data</code>.</dd>
<dt>casrn.vector</dt>
<dd>For vector or single value, CAS number</dd>
<dt>this.pH</dt>
<dd>pH of media</dd></dl>

Arguments

Author

Parameterize In Vitro Distribution Models — parameterize_IVD

<dl>

<dt>tcdata</dt>
<dd>A data.table with casrn, nomconc, MP, gkow, gkaw, gswat, sarea,
v_total, v_working. Otherwise supply single values to this.params (e.g., this.sarea,
this.v_total, etc.). Chemical parameters are taken from 
<code>chem.physical_and_invitro.data</code>.</dd>


<dt>casrn.vector</dt>
<dd>For vector or single value, CAS number</dd>


<dt>this.pH</dt>
<dd>pH of media</dd>

</dl>

Parameterize In Vitro Distribution Models

Param	Description	Units
casrn	Chemical Abstracts Service Registry Number	character
logHenry	The log10 Henry's law constant	atm*m^3/mol
gswat	The log10 water solubility at 25C (logWSol)	log10 mol/L
MP_C	The chemical compound's melting point	degrees C
MW	The chemical compound's molecular weight	g/mol
gkow_n	The log10 octanol to water (PC) (logP)	log10 unitless ratio
pKa_Donor	Chemical dissociation equilibrium constant(s); pKa(ie pKa_Donor) = -log10(Ka)	unitless
pKa_Accept	Chemical association equilibrium constant(s); pKb(ie pKa_Accept) = 14 - pKa	unitless
pH	pH where ionization is evaluated (typically assay medium)	unitless
gkaw_n	The air to water PC (neutral)	unitless ratio

parameterize_IVD: Parameterize In Vitro Distribution Models

Description

Usage

Value

Arguments

Author

Examples