Translobular uptake patterns of environmental toxicants in the rat liver.

Abstract

Recent autologous blood perfusion and autoradiographic studies in this laboratory have shown that uptake of the organophosphate insecticide, parathion and its metabolite, paraoxon, by the rat liver is extremely rapid. The efficient metabolism of these organophosphorus esters during the first hepatic passage results from a favorable combination of two independent factors, i.e., the titer of biodegradation enzymes within the lobule and the mode of translobular uptake. If this scenario also applies to other chemicals, it may be possible to define their threshold doses for systemic exposure. Such a possibility has far-reaching toxicological implications, and prompted this study to explore the less defined of the two underlying factors, i.e., translobular uptake pattern of xenobiotics using the recently developed autologous blood recirculating liver perfusion technique. The authors have limited themselves to non-ionic chemicals to avoid complications due to active transport. Because water solubility/lipophilicity is likely to be a critical factor in the binding of xenobiotics to the blood and hepatocytes and thus in their translobular behavior, xenobiotics of varied lipophilicity were pulse-infused and their elution pattern examined in the recirculating autologous blood perfusion system. Three chemicals, i.e., 1,2- and 1,3-dichlorobenzene and 4-nitroanisole were chosen as examples of relatively water-soluble xenobiotics compared with more » parathion. Benzo(a)pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin were studied as highly lipophilic toxicants. « less