Software Description
The PBPK model (version 2.00) is a physiologically-based pharmacokinetic fugacity model of a human which describes the disposition of a specified environmental contaminant. The model calculates time-dependent concentrations of the chemical in blood and five tissue groups (liver, fat, skin, and richly and slowly perfused tissue) from any or all of the following exposure media: respired air, ingested food and water, and an external dermal exposure medium, possibly water during bathing. The chemical may be introduced by an exposure with a constant, pulse, step, or sinusoidal time-dependent function, or, in the case of the respired air, from the file generated by the Indoor model.
This model is mechanistic in structure and requires physical-chemical partitioning and biotransformation data. It is designed to complement environmental fate models, thus linking chemical emission rates with environmental and physiological behaviour as part of the larger environmental risk assessment process.
This model has been designed to be loosely coupled with the Indoor model (version 2.00) that generates time-dependent concentrations of contaminants in a defined indoor environment from, for example, volatile chemicals present in water used for showering. Either model may also be used on its own.
This model is useful for estimating the relative concentrations in various tissues, the residence time or persistence of the chemical in the body and the primary rates of loss, for example by biotransformation or exhalation. The user can explore the sensitivity of the desired results to variation in input parameters by incremental adjustment of these parameters on a one-by-one or combined basis.
Features of the PBPK model:
- Provides a database of chemicals and chemical properties that may be added to or modified by the user.
- Provides a database of humans and human properties that may be added to or modified by the user.
- Provides context-sensitive Help.
- Allows on-screen display or printing of the model results (including inputs).
- Provides an on-screen diagram of chemical movement into, out of and within the body.
- Provides on-screen time course charts of chemical uptake and loss.
- Displays and prints the model calculations, as performed by the program.
- Allows the program results to be saved as a comma separated (csv) text file viewable by most standard spreadsheet software for subsequent analysis or graphing.
This program was based on the following publication:
- Cahill, T.M., Cousins, I., Mackay, D. “Development and application of a generalized physiologically based pharmacokinetic model for multiple environmental contaminants”. 2003. 22(1): 26-34.
The required input data are:
Chemical Properties
- Chemical name
- Molar mass
- Chemical type (currently only Type 1 chemicals are treated by this model)
- Data temperature
- Log (octanol - water partition coefficient), log KOW
- Water solubility and vapour pressure
- Melting point
- Tissue-air partition coefficients may be input directly or calculated from the water solubility, vapour pressure and KOW
- Biotransformation half-lives in venous blood, arterial blood, fat tissues, richly and slowly perfused tissues, and skin
- Michaelis-Menten parameters for biotransformation in the liver
- Skin permeability mass transfer coefficient
Human Properties
- Total mass
- Volume, density and lipid fraction fraction of venous blood, arterial blood, fat tissues, richly and slowly perfused tissues, liver tissues and skin
- Blood flow rate through fat tissues, richly and slowly perfused tissues, liver tissues and skin as a percentage of the total cardiac output
- Body temperature (not used)
- Total cardiac output
- Ventilation rate (i.e., breathing rate)
- Efficiency of uptake through breathing
- Total ingestion rate (includes both food and water)
- Gut efficiency
- Area of exposed skin
- Total area of skin (not used)
- Density of food
- Phase fractions in food and external medium in contact with the skin, that is, the fractions of air, water, and lipid
Initial Contamination of Human:
This is set by selecting one of the following options
- "pristine" assumes initial fugacities of zero in all human body compartments
- "From environmental steady-state concentrations" initial fugacities in all human body compartments are calculated from user-input concentrations in air, food (including water) and the external medium in contact with the skin
- "Set initial fugacities manually" initial fugacities in all human body compartments are set manually by the user
Simulation Times
- Time step
- Total simulation time
- Number of result steps to be displayed, saved, or printed
Dynamic Environmental Concentrations
- The file or function best describing the concentrations in each of the environmental media, air, food (including water), and external medium in contact with the skin
Model output includes
- All input parameters including chemical and human properties, initial contamination of the human, the dynamic environmental concentrations and all parameters derived from these inputs
- The concentration, fugacity, fugacity capacity (Z), and amount of chemical in each body compartment
- The chemical fluxes between the environment and the body and the blood and the various body tissues
- The chemical losses due to biotransformation in each body compartment
- The D values for each flux or loss process
- A diagram of chemical movement into, out of and within the body
- Time course charts of chemical loss and uptake
Please read the software license before downloading the software. Use of the software constitutes your agreement to abide by the terms and conditions set out in the license agreement.