In order to understand the splenic toxicity of aniline in rats, early interaction of aniline with erythrocytes and its subsequent deposition and covalent binding to macromolecules in target (spleen) and nontarget (liver) organs have been studied. Male Sprague-Dawley (SD) rats were given 1 or 3 doses of 1 mmol/kg [14CJaniline hydrochloride (1 dose/d) by gavage and euthanized 24 h after the treatment. Among blood components, maximum radioactivity was found to be associated with red blood cells (RBCs). After 3 doses, there was 112, 79, and 67% increase in the radioactivity in the whole blood, RBCs, and hemolysate, respectively, in comparison to 1 dose. In comparison to RBCs, plasma had only 40 and 16% radioactivity after the administration of 1 and 3 doses, respectively. Spleen homogenate at 1 dose had one-third of the radioactivity in the TCA precipitate, which increased to 40% at 3 doses, while the total radioactivity increased 256% over 1 dose. Liver, which had almost double the radioactivity on a per gram tissue basis compared to the spleen at one dose, did not show any appreciable increase in the radioactivity at three doses. However, radioactivity in the TCA precipitate of liver homogenate increased by 92% after 3 doses. The iron content of the spleen in rats given 3 doses of [14C]aniline increased by 85% compared to the rats given just 1 dose. The iron content of liver did not show any change at three doses. These data thus demonstrate a dose-dependent binding and accumulation of radioactivity in erythrocytes and spleen. These interactions, along with parallel increases in the iron content of the spleen, could be critical in the splenic toxicity of anilines.
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