Effects of chlorpropham (CIPC) on the hemopoietic system of rats

Male F344 rats were given 0 or 3% chlorpropham in the diet and at 2, 4. 6, 8 or 13 weeks of administration, five rats in each group were examined for hematology, plasma clinical chemistry and pathology. Marked splenomegaly an d hepatomegaly were observed in treated rats at 2-13 weeks of administratio n. Red blood cell counts, hemoglobin concentration, packed cell volume and platelet counts were significantly decreased and methemoglobin level, mean corpuscular volume and white blood cell counts were significantly increased in treated rats at 2-13 weeks of administration. The covalent binding of m -chloraniline m-CA, (the hydrolytic metabolite of chlorpropham) was observe d in hemoglobin or splenic protein of treated rats, but only small amounts of Free m-CA were present in blood or spleen. Congestion, hemosiderin depos its, extramedullary hemopoiesis and lymphoid atrophy in spleen and hyperpla sia of hemopoietic cells in bone marrow were observed in treated rats at 2- 13 weeks and fibrosis in splenic capsule were observed in treated rats at 4 -13 weeks. The pathological changes in spleen rather than hematological cha nges progressed during administration, suggesting splenotoxicity of CIPC in rats. (C) 2001 Elsevier Science Ltd. All rights reserved.