Relationship between benzene toxicity and the disposition of 14C-labelled benzene metabolites in the rat

Abstract

The distribution of radioactivity associated with three 14C-labelled benzene metabolites was studied using whole body autoradiography (WBAR). Male Fischer-344 rats were given an intravenous dose of 0.6 mg/kg (60 microCi phenol, 1.2 mg/kg (100 microCi) catechol, or 1.3 mg/kg (100 microCi) hydroquinone. The rats were killed after 2 h and autoradiograms were prepared from whole body sagittal sections. The relative organ uptake of radioactivity associated with each compound was assessed by comparing tissue/blood optical density (O.D.) ratios from X-ray films. Bone marrow, thymus and the white pulp of the spleen concentrated radioactivity associated with hydroquinone or catechol. Radioactivity associated with phenol concentrated in the red pulp of the spleen, but not in the other lymphoid tissues. Radioactivity associated with all three metabolites was found in the lungs, kidneys and small intestines, whereas greater accumulation of radioactivity was observed in subcutaneous tissues, sebaceous glands and the white matter of the brain and spinal cord in rats given hydroquinone or catechol than in animals given phenol. Rats pretreated with a single dose of Aroclor 1254 (250 mg/kg, i.p.), a regimen which was found to protect against benzene-induced lymphocytopenia, were given hydroquinone (100 microCi; 1.3 mg/kg) or catechol (100 microCi; 1.4 mg/kg). For hydroquinone the tissue/blood O.D. ratios for bone marrow and thymus were approx. 60% lower in Aroclor-pretreated than in untreated rats. A 25% reduction in the tissue/blood O.D. ratios for these organs was observed in pretreated rats given catechol. These findings indicate that the uptake and concentration of radioactivity associated with hydroquinone and catechol by bone marrow and lymphoid organs (1) can occur independently of the metabolism of benzene in these tissues and (2) is reduced under conditions in which the animal is less susceptible to benzene toxicity.