Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats

In the present study, we investigated the toxic response to repeated oral administration of 2-chloroethyl linoleate (2-CEL) in male rats at 250 mg/kg body weight for 2 weeks on alternate days (total 7 doses). Control rats received an equal volume of mineral oil. The five animals from each group were sacrificed on days 1, 7 and 28 following the last dose. No significant changes were observed in body weight, as well as organ-to-body weight ratios due to 2-CEL treatment. The red blood cell counts increased significantly in 2-CEL treated animals at day 28 as compared to the controls. Elevated counts of platelets, monocytes and eosinophils and low counts of basophils and large unstained cells were also observed at some time points in 2-CEL treated rats. Significantly reduced activities of total serum lactate dehydrogenase (LDH), aspartate aminotransferase and alanine aminotransferase were found at most of the time points except for LDH at day 28. Adenosine triphosphatase activity was also significantly reduced in liver mitochondrial fraction at all time points. Histopathological studies showed consistent centrilobular lesions (incidence 4/4) in the liver consisting of hepatocyte vacuolar degeneration and focal necrosis at day 28. A few centrilobular lesions were also observed (incidence 2/4) at day 7, while no changes were observed at day 1. These results indicate that 2-CEL is a hepatotoxin, however, the observed decrease in serum enzyme levels in relation to hepatotoxicity of 2-CEL, needs to be elucidated.