Statistical aspects of inhalation toxicokinetics

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.

[1]  Keith Godfrey,et al.  Compartmental Models and Their Application , 1983 .

[2]  J. Filser,et al.  The closed chamber technique — uptake, endogenous production, excretion, steady-state kinetics and rates of metabolism of gases and vapors , 2006, Archives of Toxicology.

[3]  H. Bolt,et al.  Statistical evaluation of toxicokinetic data , 1993 .

[4]  H. Bolt,et al.  Statistical analysis of toxicokinetic data by nonlinear regression (example: inhalation pharmacokinetics of propylene) , 2005, Archives of Toxicology.

[5]  K. Golka,et al.  Pharmacokinetics of propylene and its reactive metabolite propylene oxide in Sprague-Dawley rats. , 1989, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[6]  James H. Matis,et al.  17 Compartmental models of ecological and environmental systems , 1994, Environmental Statistics.

[7]  Walter W. Piegorsch,et al.  15 Environmental biometry: Assessing impacts of environmental stimuli via animal and microbial laboratory studies , 1994, Environmental Statistics.

[8]  K. Bellmann,et al.  Jacquez, J. A.: Compartmental analysis. Biology and Medicine. Elsevier Publ. Co., Amsterdam, New York 1972. XIV, 237 S., 93 Abb., 1 Tab., $24.35 , 1974 .

[9]  D G Hoel,et al.  Implication of nonlinear kinetics on risk estimation in carcinogenesis. , 1983, Science.

[10]  J. Jacquez Compartmental analysis in biology and medicine , 1985 .

[11]  G. Csanády,et al.  Statistical analysis of toxicokinetic data by nonlinear regression , 2005, Archives of Toxicology.