ICE_IVIVEpipeline

The workflow allows the flexibility to select from three different rat and human PK models: a 1 compartment model that incorporates Monte Carlo simulation to simulate the population variance (1C), 3 compartment model leveraging the EPA's httk package (Solve_3comp) and (solve_pbtk). The workflow is to predict the daily equivalent administered dose (EAD, mg/kg/day) that would lead to steady state blood concentration equivalent to the bioactive concentration from in vitro assays and compared to the predicted lowest effective levels (LELs) of in vivo assays, which is user provided

Required libraries

library(tidyverse)
library(deSolve) # Solves for initial value problems of differential equations
library(doParallel) # for parallelization 
library(httk) #this is needed for models: solve_3comp, solve_pbtk. The code is compatible with httk_2.0.2

Input files

ChemicalData_Rnotebook.txt: example data file of the chemical property data needed to run the workflow
InvitroData_Rnotebook.txt: example data file of the in vitro assay data needed to run the workflow. Note that the first column must be a CASRN and the following columns assay response values in units matching those that the plasma concentration of chemical are in

Code files

steadyState.R: the 1 compartment tk model that calculates a steady state plasma concentration of a given chemical
CalcEAD.R: calculates the estimated administered dose based on a given plasma concentration and invitro tests
EADboxplot.R: generates boxplots of the EAD values for each chemical based on the in vitro activity concentrations
ICE_IVIVE.Rmd: the R notebook with the workflow code

ICE_PBPKpipeline

The workflow allows the flexibility to select from two different rat and human PK models from the EPA’s httk package: (solve_pbtk), and (Solve_gas_pbtk). The workflow is to predict plasma and tissue concentration profiles across time following a dose of a substance. Exposure routes include oral ingestion (solve_pbtk), intrevenous (solve_pbtk), and inhalation (solve_gas_pbtk). For inhalation exposures using the dose is provided as an air concentration.

Required libraries

library(tidyverse)
library(deSolve)
library(doParallel)
library(httk)  #this is needed for models: Solve_3comp, Solve_pbtk. # The code is compatible with httk_2.0.2
library(openxlsx)  #for writing the excel file that is user output
library(data.table)

Input files

ChemicalData_Rnotebook.txt