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Estimation of toxicokinetic population parameters in a four-stage hierarchical model

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  • Selinski, Silvia

Abstract

A basic part in the risk assessment of potential carcinogens is the determination of toxicokinetic parameters. The partition of the xenobiotic in the body of experimental animals is a first step of the biochemical pathway of the formation of DNA adducts which might lead to the development of cancer. Fundamental in the extrapolation from one species to another is the characterisation of processes by means of population parameters. Nevertheless, the consideration of individual parameters varying between repeated experiments and different doses is of great importance to obtain a more precise insight into the variability structure of the process so that a valid basis for further research is the final result. Two nonlinear four-stage hierarchical models for a repeated measurement design and for repeated exposures to different doses are presented. The estimation of the individual and population parameters as well as of the covariance matrices is performed by an EM algorithm.

Suggested Citation

  • Selinski, Silvia, 2000. "Estimation of toxicokinetic population parameters in a four-stage hierarchical model," Technical Reports 2000,01, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    • Handle: RePEc:zbw:sfb475:200001
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    File URL: https://www.econstor.eu/bitstream/10419/77310/2/2000-01.pdf
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    References listed on IDEAS

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    1. Becka, Michael, 1998. "Complexity-reduction by first-order approximation of non-linear kinetics," Technical Reports 1998,04, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    2. Selinski, Silvia & Urfer, Wolfgang, 1998. "Interindividual and interoccasion variability of toxicokinetic parameters in population models," Technical Reports 1998,38, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
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    1. Quinke, Barbara & Selinski, Silvia & Golka, Klaus & Blaszkewicz, M., 2000. "Population toxicokinetics of ethylene: Calibration and preceding investigations," Technical Reports 2000,03, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    2. Schirm, Florian A. & Selinski, Silvia, 2000. "Interindividual and interoccasion variability of toxicokinetic parameters of uptake, exhalation, and metabolism of ethylene," Technical Reports 2000,07, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    3. Selinski, Silvia & Becker, Claudia, 2001. "Outlier detection in experimental data using a modified Hampel identifier," Technical Reports 2001,40, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.
    4. Brunnert, Marcus & Müller, Oliver & Urfer, Wolfgang, 2000. "Genetical and statistical aspects of polymerase chain reactions," Technical Reports 2000,06, Technische Universität Dortmund, Sonderforschungsbereich 475: Komplexitätsreduktion in multivariaten Datenstrukturen.

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