HEMOTOXIC EFFECT OF PHENYLUREA HERBICIDES IN RATS - ROLE OF HEMOGLOBIN-ADDUCT FORMATION IN SPLENIC TOXICITY

Three substituted phenylurea herbicides were used for the study of the haemotoxic effects on rats of chronic exposure to these compounds. Fe male Sprague Dawley rats were given monuron, diuron or fenuron (250-1 000 mg/kg diet) for 14 months. The final body weights were similar to those of controls. No treatment-related effects on organ weights were observed at autopsy, except for a dose-related increase in spleen weig hts in rats treated with monuron or diuron, but not in those treated w ith fenuron. The proportion of haemoglobin in the form of methaemoglob in increased in the dosed group and resulted in a secondary anaemia wi th changes in the morphology of erythrocytes. Haemoglobin adducts of a romatic amines released from the herbicides were present at dose-relat ed levels in rats treated with monuron or diuron. Compound-related les ions were observed histologically in treated rats, with increased pigm entation (haemosiderin) in the spleen, reflecting the response to the haemolytic anaemia and methaemoglobinaemia induced by the herbicides. Pigment deposition consisting of golden brown granules in the cytoplas m of the tubular epithelium in the kidney and in the Kupffer cells in the liver were observed only in rals treated with monuron. The haemoto xic effects that were observed may indicate that the formation of addu cts between haemoglobin and the parent aromatic amines released metabo lically from these herbicides has a role in the splenic toxicity of th ese compounds.