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>).">

httk: High-Throughput Toxicokinetics (original) (raw)

Author:

John Wambaugh ORCID iD [aut, cre], Sarah Davidson-FritzORCID iD [aut], Robert Pearce ORCID iD [aut], Caroline Ring ORCID iD [aut], Greg Honda ORCID iD [aut], Mark Sfeir [aut], Matt Linakis ORCID iD [aut], Dustin Kapraun ORCID iD [aut], Kimberly Truong ORCID iD [aut], Colin Thomson ORCID iD [aut], Meredith Scherer ORCID iD [aut], Annabel Meade ORCID iD [aut], Celia Schacht ORCID iD [aut], Leonie Lautz ORCID iD [aut], Todor Antonijevic ORCID iD [ctb], Miyuki Breen ORCID iD [ctb], Shannon Bell ORCID iD [ctb], Xiaoqing Chang ORCID iD [ctb], Jimena Davis [ctb], Elaina Kenyon ORCID iD [ctb], Gilberto Padilla MercadoORCID iD [ctb], Katie Paul FriedmanORCID iD [ctb], Nathan Pollesch ORCID iD [ctb], Noelle Sinski [ctb], Nisha Sipes ORCID iD [ctb], James Sluka ORCID iD [ctb], Caroline Stevens ORCID iD [ctb], Barbara Wetmore ORCID iD [ctb], Lily Whipple [ctb], Woodrow Setzer ORCID iD [ctb]