Haemotoxic effect of phenylurea herbicides in rats: role of haemoglobin-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. Female Sprague-Dawley rats were given monuron, diuron or fenuron (250-1000 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 weights in rats treated with monuron or diuron, but not in those treated with fenuron. The proportion of haemoglobin in the form of methaemoglobin increased in the dosed group and resulted in a secondary anaemia with changes in the morphology of erythrocytes. Haemoglobin adducts of aromatic amines released from the herbicides were present at dose-related levels in rats treated with monuron or diuron. Compound-related lesions were observed histologically in treated rats, with increased pigmentation (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 cytoplasm of the tubular epithelium in the kidney and in the Kupffer cells in the liver were observed only in rats treated with monuron. The haemotoxic effects that were observed may indicate that the formation of adducts between haemoglobin and the parent aromatic amines released metabolically from these herbicides has a role in the splenic toxicity of these compounds.
Wang
S W
SW
Institute of Biochemistry, Chung Shan Medical and Dental College, Taichung, Taiwan, Republic of China.
Chu
C Y
CY
Hsu
J D
JD
Wang
C J
CJ
D000818:Animals; D001769:Blood / Q000187:drug effects*; D002849:Chromatography, Gas; D004237:Diuron / Q000633:toxicity; D005260:Female; D006403:Hematologic Tests; D006454:Hemoglobins / Q000187:drug effects*; D006540:Herbicides / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects; D008782:Methylurea Compounds / Q000633:toxicity; D010671:Phenylurea Compounds / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
D006454:Hemoglobins; D006540:Herbicides; D008782:Methylurea Compounds; D010671:Phenylurea Compounds; D004237:Diuron; C100088:monuron; C010727:fenuron