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Statistical aspects of inhalation toxicokinetics
Authors:Michael Becka  Wolfgand Urfer
Institution:(1) Bayer AG, Biometry Europe, D-42096 Wuppertal, Germany;(2) Department of Statistics, University of Dortmund, D-44221 Dortmund, Germany
Abstract:The statistical analysis of dynamic processes is a useful tool to learn how environmental and ecological systems work and how they respond to disturbances. In the context of human risk assessment of potentially harmful chemicals, many complex dynamic processes in terms of kinetics have to be taken into account. Thorough research of direct influence of chemicals to humans depends on investigations with animalsin vivo andin vitro. However, when animals serve as models of human systems, one critical step is the extrapolation from the risk observed in the experimental animals to the risk associated with the human organism. To extrapolate the observed risk in this case, the detailed knowledge of the relevant kinetic processes as well as their differences between species is fundamental. On the other hand experimental tools for these processes are quite restrictive. Based on simple experimental designs a statistical method is proposed for characterizing such kinetic processes using the well-known compartmental analysis tool and non-linear regression. The methodology is then exemplified by non-invasive toxicokinetic inhalation experiments with rats.
Keywords:Deterministic compartmental model  dynamic system  kinetic process  nonlinear regression  toxicology
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