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Physiologically based toxicokinetic modeling of 1,3-butadiene lung metabolism in mice becomes more important at low doses.

Evelo CT, Oostendorp JG, ten Berge WF, Borm PJ - Environ. Health Perspect. (1993)

Bottom Line: With the resulting model, the relative importance of lung metabolism as compared to metabolism in the liver increased with decreasing ambient air concentrations.The tendency toward increased importance of lung metabolism at low doses indicates the necessity of careful extrapolation of in vivo results to low doses.Moreover, this trend may also contribute to species difference in susceptibility to the carcinogenic activity of butadiene.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.

ABSTRACT
This paper describes a physiologically based toxicokinetic model for 1,3-butadiene uptake, distribution, and metabolic clearance in mice. Model parameters for metabolic activity were estimated from the correspondence between computer simulation studies and experimental results as published in the literature. The parameterized model was validated with independent literature data. With the resulting model, the relative importance of lung metabolism as compared to metabolism in the liver increased with decreasing ambient air concentrations. This was due to saturation of metabolism in the alveolar area of the lung, which occurred in the simulations at ambient air concentrations well below current threshold limit values. At higher air concentration, liver metabolism became relatively more important. The tendency toward increased importance of lung metabolism at low doses indicates the necessity of careful extrapolation of in vivo results to low doses. Moreover, this trend may also contribute to species difference in susceptibility to the carcinogenic activity of butadiene.

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Physiologically based toxicokinetic modeling of 1,3-butadiene lung metabolism in mice becomes more important at low doses.

Evelo CT, Oostendorp JG, ten Berge WF, Borm PJ - Environ. Health Perspect. (1993)

© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1519919&req=5

Bottom Line: With the resulting model, the relative importance of lung metabolism as compared to metabolism in the liver increased with decreasing ambient air concentrations.The tendency toward increased importance of lung metabolism at low doses indicates the necessity of careful extrapolation of in vivo results to low doses.Moreover, this trend may also contribute to species difference in susceptibility to the carcinogenic activity of butadiene.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.

ABSTRACT
This paper describes a physiologically based toxicokinetic model for 1,3-butadiene uptake, distribution, and metabolic clearance in mice. Model parameters for metabolic activity were estimated from the correspondence between computer simulation studies and experimental results as published in the literature. The parameterized model was validated with independent literature data. With the resulting model, the relative importance of lung metabolism as compared to metabolism in the liver increased with decreasing ambient air concentrations. This was due to saturation of metabolism in the alveolar area of the lung, which occurred in the simulations at ambient air concentrations well below current threshold limit values. At higher air concentration, liver metabolism became relatively more important. The tendency toward increased importance of lung metabolism at low doses indicates the necessity of careful extrapolation of in vivo results to low doses. Moreover, this trend may also contribute to species difference in susceptibility to the carcinogenic activity of butadiene.

Show MeSH