Toxicity, tissue distribution, and excretion of benzyl chloride in the rat

The tissue distribution and excretion of [14C]benzyl chloride was investigated in adult male and female Fischer 344/N rats after administration of a single oral dose of [14C]benzyl chloride in corn oil at 25 mg/kg, data was correlated with histopathologic and toxicity findings elicited from a 27-37-wk repeated-dose oral toxicity study of benzyl chloride. Radioactivity was detected in all tissues selected for examination. Elimination of the isotope occurred predominantly in the urine. Female rats excreted the isotope at a faster rate than the males and also maintained slightly lower tissue concentrations (with the exception of the blood and kidneys). Isotope recovery was achieved at 90% in the urine and feces of female rats at 24 h, compared with an 80% recovery rate in males. Concentrations of radioactivity were high in the gastrointestinal tract, reflecting the route of administration; however, the squamous stomach and the small intestine consistently retained higher concentrations of isotope than the glandular stomach. Results of acute toxicity and organ histopathology studies in animals dosed with benzyl chloride for 27-37 wk are compatible with the organ distribution and excretion of [14C]benzyl chloride. Histopathologic findings included severe acute and chronic gastritis, hyperkeratosis and hyperplasia of the squamous stomach, and progressive lesions of the heart ranging from proliferation of interstitial cells to acute necrosis of myocardial fibers. Both of these studies suggest that the squamous stomach is a target organ for benzyl chloride or one of its metabolites.