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R Package "httkexamples"

High throughput toxicokinetics ("HTTK") is the combination of in vitro data and generic mathematical models to predict absorption, distribution, metabolism, and excretion by the body, as decribed by Pearce et al. (2017) (doi:10.18637/jss.v079.i04) and Breen et al. (2021) (doi:10.1080/17425255.2021.1935867). We provide examples (vignettes) applying HTTK to solve various problems in bioinformatics, toxicology, and exposure science. In accordance with Davidson-Fritz et al. (2025) (doi:10.1371/journal.pone.0321321), whenever a new HTTK model is developed, the code to generate the figures evaluating that model is added as a new vignettte.

Loading the httk walkthroughs ("vignettes")

List all vignettes for httk

httk.vignettes()

Displays the vignette for a specified vignette

vignette("IntroToHTTK")

Authors

Principal Investigator

John Wambaugh [John.Wambaugh@UL.org]

Vignette Authors

Robert Pearce, Caroline Ring [Ring.Caroline@epa.gov], Greg Honda [honda.gregory@epa.gov], Matt Linakis [MLINAKIS@ramboll.com], Dustin Kapraun [kapraun.dustin@epa.gov], Kimberly Truong [truong.kimberly@epa.gov], Annabel Meade [aemeade7@gmail.com], Celia Schacht [Schacht.Celia@epa.gov], and Elaina Kenyon

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Version

Install

install.packages('httkexamples')

Version

0.0.1

License

MIT + file LICENSE

Maintainer

John Wambaugh

Last Published

December 10th, 2025

Functions in httkexamples (0.0.1)

Huh et al. 2011 Huh et al. (2011) (tools:::Rd_expr_doi("10.3109/00498254.2011.598582")) provided interspecies allometric scaling parameters for whole body clearance for a a variety of pharmaceuticals.

Wallis et al. 2023 Wallis et al. (2023) (tools:::Rd_expr_doi("10.1021/acs.est.2c08241")) estimated the human toxicokinetic half-lives for a range of per- and poly-fluorinated alkyl substances (PFAS).

in vitro Toxicokinetic Data from Wambaugh et al. (2019)

NHANES Exposure Data

SEEM3 Example Data for Truong et al. 2025

Partition Coefficients from PK-Sim

Johnson et al. (2006)

Simulation outputs from Meade et al. (submitted) Meade et al. (submitted) performed generic PBTK simulations for dermal exposure under a variety of assumptions. Although the code to recreate these simulations is provided, it is time-intensive. The 2025 outputs from the simulations are stored in this list of data.frames.

ToxCast thyroid-related bioactivity data

Wang et al. 2018 Wang et al. (2018) screened the blood of 75 pregnant women for the presence of environmental organic acids (EOAs) and identified mass spectral features corresponding to 453 chemical formulae of which 48 could be mapped to likely structures. Of the 48 with tentative structures the identity of six were confirmed with available chemical standards.

pregnonpregaucs

AUCs for Pregnant and Non-Pregnant Women

supptab2_Linakis2020

More supplementary output from Linakis 2020 vignette analysis.

wambaugh2019.nhanes

NHANES Chemical Intake Rates for chemicals in Wambaugh et al. (2019)

Toxicokinetic concentration vs. time (CvT) data for Meade et al. (submitted) chemicals Meade et al. (submitted) evaluated a generic PBTK model for dermal exposure using in vivo CvT data curated from the literature. These data will eventually be incorporated in the the CvTdb (Sayre et al., 2020, tools:::Rd_expr_doi("10.1038/s41597-020-0455-1")).

wambaugh2019.raw

Raw Bayesian in vitro Toxicokinetic Data Analysis from Wambaugh et al. (2019)

supptab1_Linakis2020

Supplementary output from Linakis 2020 vignette analysis.

Chemicals with ToxCast data for Meade et al. (submitted) chemicals Meade et al. (submitted) performed in vitro-in vivo extrapolation for dermal exposures assuming 8 hours of exposure via hands submerged in a liquid with 1 ppm of chemical. These are the ToxCast in vitro screening data for those chemicals.

DRUGS|NORMAN: Pharmaceutical List with EU, Swiss, US Consumption Data

wambaugh2019.tox21

Tox21 2015 Active Hit Calls (EPA)

Partition Coefficient Data

wambaugh2019.seem3

ExpoCast SEEM3 Consensus Exposure Model Predictions for Chemical Intake Rates

dermal.nonvolatilechems

Non-volatile chemicals with ToxCast data Meade et al. (submitted) performed in vitro-in vivo extrapolation for dermal exposures assuming 8 hours of exposure via hands submerged in a liquid with 1 ppm of chemical. These were the chemicals analyzed.

Scherer2025.IVD

Literature Measurements of In Vitro Cellular and Nominal Concentration

Aylward et al. 2014

concentration_data_Linakis2020

Concentration data involved in Linakis 2020 vignette analysis.

Howgate et al. (2006)

Fetal Partition Coefficients

Abraham et al. 2024 Abraham et al. (2024) (tools:::Rd_expr_doi("10.1016/j.envint.2024.109047")) determined the half-lives of 15 per- and polyfluoroalkyl substances in a single male volunteer.

Published toxicokinetic predictions based on in vitro data from Wetmore et al. 2012.

Dimitrijevic.IVD

Dimitrijevic et al. (2022)In Vitro Cellular and Nominal Concentration

Parameters for in vitro distribution analysis in Honda et al. (2019) Honda et al. (2019) (tools:::Rd_expr_doi("10.1371/journal.pone.0217564")) used the Armitage et al. (2014) (tools:::Rd_expr_doi("10.1021/es501955g")) mass-balance model to predict the impact of in vitro partitioning on free chemical concentrations.

Frank2018invivo

Literature In Vivo Data on Doses Causing Neurological Effects

Published Pharmacokinetic Parameters from Obach et al. 2008

httkexamples-package

httkexamples: High-Throughput Toxicokinetics Examples

metabolism_data_Linakis2020

Metabolism data involved in Linakis et al. 2020 (tools:::Rd_expr_doi("10.1038/s41370-020-0238-y")) vignette analysis.