La toxicocinétique prédictive

Abstract : Dose-effect relationships in chemical risk assessment are commonly derived through simple mathematical models linking directly effects with exposure dose. These models, usually calibrated with animal data, are specific to the tested chemical, the endpoint and the experimental protocol. Accounting for toxicokinetics permit to extrapolate results for different chemicals and different scenarios of exposure. Among toxicokinetics models, physiologically based pharmacockinetic (PBPK) models are based on a realistic description of anatomy, physiology and of the mechanisms involved in the disposition of a compound within an organism, i.e. absorption, distribution, metabolism, and excretion (ADME processes). We present three examples of use of toxicokinetics models in risk assessment. In the first one, we contributed to an INRS study aiming at evaluating workers cobalt exposure. The second one consists in the recent development of a generic lifetime PBPK model accounting for physiological differences between individuals. The third one exposes the calibration of a PBPK model based on imaging data to assess the kinetics of inhaled particles.
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Alexandre Pery. La toxicocinétique prédictive. Rapport Scientifique INERIS, 2010, 2009-2010, pp.48-50. ⟨ineris-01869275⟩

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