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Med. Pr. 2001;52(5)

Specific nature of the software used to construct simulations: physiologically-based toxicokinetic models

Specyfika stosowanego oprogramowania w konstruowaniu symulacyjnych, fizjologicznych modeli toksykokinetycznych (PBTK)

P. Jałowiecki, P. Kostrzewski

Abstract

Building of the physiologically-based toxicokinetic (PBTK)models is based on the application of simulation languages, such as advanced continuous simulation language (ACSL).
The aim of this study was to develop the principles of constructing the fundamental model and the models dedicated to chemicals found in the work environment (e.g. trimethylbenzene (TMB) isomers present in the petrochemical, paint and lacquer and related industries).
The fundamental model is based on four main compartments (fat tissues, richly perfused tissue, slowly perfused tissue and liver) and six auxiliary compartments (lungs, venous blood, arterial blood, body weight, inhaled air and exhaled air).
The basic element of the PBTK model comprises blocks containingdefinitions of variables and constants supplemented by the following parameters: command, calculated, transferred and resulted.
The models dedicated to various chemicals and organisms are built by a suitable modification of the fundamental model. All sets of command parameters values for the organism, chemical and simulation are written in the text files and loaded before or during the simulation. The empirical data obtained in experiments with volunteers are used in a similar way. The specimen dedicated model was built for 1,2,3-TMB (hemimellitene).
2,3-Dimethylbenzoic acid (2,3,-DMBA) (a hemimelitene metabolite) excretion rate data obtained from an experiment during which volunteers were exposed to hemimellitene at 25 at 100 mg/m³ were compared with the results of the computer simulation. A high convergence of the comparable values was obtained. Simulations were also made for exposure periods of one week and one month. The results confirmed the experiment-based recommendations on the assessment of the occupational exposure.
The application of the new physiologically-based toxicokinetic models renders it possible to forecast toxic chemical (or it metabolite) concentrations corresponding to the concentrations of those chemicals in the workplace atmosphere.

Key words

physiological toxicokinetic models, fundamental model, dedicated model