IndusChemFate PBTK Model - R Implementation

This repository contains two R implementations of the IndusChemFate Physiologically Based ToxicoKinetic (PBTK) model, which was originally developed in Visual Basic for MS Excel by Frans Jongeneelen and Wil ten Berge.

Overview

IndusChemFate is a multi-chemical PBTK model designed to estimate blood and urine concentrations of chemicals and their metabolites under various exposure scenarios. The model is capable of simulating:

• Multiple exposure routes (inhalation, dermal, and oral)
• Various human subjects (adult males, adult females, children with normal weight and obese)
• Experimental animals (rat and mouse)
• Different activity levels (at rest and light work)
• Metabolism and elimination of parent compounds and metabolites

Original Model

The original IndusChemFate model (version 2.0) was developed as an MS Excel application with Visual Basic code and is available as freeware from the CEFIC-LRI website.

Original Authors:

• Frans Jongeneelen, IndusTox Consult
• Wil ten Berge, Santoxar

Original Publication:

• Jongeneelen, F.J. and ten Berge, W.F. (2011). A Generic, Cross-Chemical Predictive PBTK Model with Multiple Entry Routes Running as Application in MS Excel; Design of the Model and Comparison of Predictions with Experimental Results. Annals of Occupational Hygiene, 55: 841-864.
• Jongeneelen, F.J. and ten Berge, W.F. (2011). Simulation of urinary excretion of 1-hydroxypyrene in various scenarios of exposure to PAH with a generic, cross-chemical predictive PBTK-model. International Archives of Occupational and Environmental Health, first online, November 2011.

R Implementations

This repository provides two R implementations of the IndusChemFate model:

1. Full Implementation (Jaqpot_service.R):

   • Complete implementation that supports up to 4 metabolites
   • Includes all 11 body compartments (adipose tissue, bone, brain, heart, kidney, intestine, liver, lung, muscle, skin, bone marrow)
   • Supports all exposure routes and physiological scenarios
   • Available at: Jaqpot Full Model

2. Lite Implementation (Lite_Jaqpot_service.R):

   • Simplified version that supports only 1 metabolite
   • Reduces computational complexity while maintaining core functionality
   • Ideal for basic toxicokinetic modeling needs
   • Available at: Jaqpot Lite Model

Key Difference: The lite version significantly reduces the model's complexity by limiting metabolite tracking to a single metabolite, making it more computationally efficient while preserving the core physiologically based toxicokinetic modeling approach.

Model Features

• Physiological Parameters: The model includes standardized physiological parameters for humans with normal weight and obesity, as well as experimental animals (rat and mouse).
• Exposure Routes: Inhalation, dermal, and oral exposure are all supported.
• Metabolism: Michaelis-Menten saturable metabolism can be modeled in any of the 11 body compartments or in liver only.
• QSPRs: The model incorporates published and in-house developed algorithms (Quantitative Structure-Property Relationships) for blood:air partitioning, tissue:blood partitioning, and renal excretion.
• Dermal Absorption: A novel dermal physiologically based module considers dermal deposition rate, duration of deposition, and evaporation during skin contact.

Required Input Parameters

Key input parameters include:

• Physical-chemical properties (molecular weight, vapor pressure, water solubility, log Kow)
• Exposure concentrations and time patterns
• Metabolism parameters (Vmax and Km)
• Selection of human or animal subject
• Exercise level

Limitations

• The model is intended as a first-tier or screening tool
• Predictions are typically accurate within an order of magnitude
• Simplified physiological processes compared to more specialized models

Attribution

The original IndusChemFate model was developed by Frans Jongeneelen and Wil ten Berge. The R implementations in this repository are provided as adaptations of their original work.

Please cite the original authors when using this model:

Jongeneelen, F.J. and ten Berge, W.F. (2011). A Generic, Cross-Chemical Predictive PBTK Model with Multiple Entry Routes Running as Application in MS Excel; Design of the Model and Comparison of Predictions with Experimental Results. Annals of Occupational Hygiene, 55: 841-864.

This adaptation of the model follows the original freeware provisions which state:

• The program may be freely distributed provided no charge is levied
• The disclaimer text is always attached
• The program is open source and improvements can be added
• If improvements are made, the name IndusChemFate may not be used
• Mirroring or reproducing any part of the program without proper reference is prohibited
• The program may not be used for commercial purposes