摘要：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. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (4.4M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 496 497 498 499 500 501 502
Loading...
