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) (tools:::Rd_expr_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 tools:::Rd_expr_doi("10.1016/j.envint.2017.06.004")) and propagating parameter uncertainty (Wambaugh et al., 2019 tools:::Rd_expr_doi("10.1093/toxsci/kfz205")). Empirically calibrated methods are included for predicting tissue:plasma partition coefficients and volume of distribution (Pearce et al., 2017 tools:::Rd_expr_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 tools:::Rd_expr_doi("10.1093/toxsci/kfv171")).
Maintainer: John Wambaugh wambaugh.john@epa.gov (ORCID)
Authors:
Sarah Davidson-Fritz davidsonfritz.sarah@epa.gov (ORCID)
Robert Pearce (ORCID)
Caroline Ring Ring.Caroline@epa.gov (ORCID)
Greg Honda honda.gregory@epa.gov (ORCID)
Mark Sfeir
Matt Linakis MLINAKIS@ramboll.com (ORCID)
Dustin Kapraun kapraun.dustin@epa.gov (ORCID)
Other contributors:
Nathan Pollesch pollesch.nathan@epa.gov (ORCID) [contributor]
Miyuki Breen breen.miyuki@epa.gov (ORCID) [contributor]
Shannon Bell Shannon.bell@inotivco.com (ORCID) [contributor]
Xiaoqing Chang Xiaoqing.chang@inotivco.com (ORCID) [contributor]
Todor Antonijevic tantonijevic@toxstrategies.com (ORCID) [contributor]
Jimena Davis [contributor]
Elaina Kenyon kenyon.elaina@epa.gov (ORCID) [contributor]
Katie Paul Friedman Paul-Friedman.Katie@epa.gov (ORCID) [contributor]
Celia Schacht Schacht.Celia@epa.gov (ORCID) [contributor]
Meredith Scherer Scherer.Meredith@epa.gov (ORCID) [contributor]
James Sluka jsluka@indiana.edu (ORCID) [contributor]
Noelle Sinski Noelle.Sinski@icf.com [contributor]
Nisha Sipes sipes.nisha@epa.gov (ORCID) [contributor]
Barbara Wetmore wetmore.barbara@epa.gov (ORCID) [contributor]
Lily Whipple [contributor]
Woodrow Setzer (ORCID) [contributor]