Lack of carcinogenicity of enzymatically modified isoquercitrin in F344/DuCrj rats

The present study was conducted to evaluate the potential carcinogenicity of enzymatically modified isoquercitrin, administered in the diet at doses of 0.5% or 1.5% to groups of 50 male and female F344/DuCrj rats. Control males and females (50 rats each) were maintained on basal diet. Animals were observed for 104 weeks. There were no treatment-related clinical signs of toxicity in the treated groups. Body weights, feed consumption, survival rates and hematological findings for exposed rats of both sexes showed no variations among the groups. There was a slight but significant dose-dependent decrease in relative spleen weights in all treated groups, albeit with no histopathological variation. Overall histopathological evaluation of neoplasms and all tissues after 2 years showed that tumors developed in all groups including the controls. There was a non-significant tendency for increase in the incidence of pituitary gland adenomas in the high dose-treated females (45.5%) as compared to controls (27.7%), with a slight increase in hemorrhage incidences, but values for males were low and similar in both control and treated rats. There were no apparent effects of isoquercitrin on development of kidney neoplasms, hyperplasias or chronic nephropathy. Parathyroid adenomas or hyperplasias were found not affected by isoquercitrin treatment, and there were no differences in mammary gland fibroadenomas or hyperplasias between treated and control rats. Various tumors were found in other organs with no significant differences between the groups. In conclusion, under the conditions of this 2-year feeding experiment, no evidence was obtained of carcinogenicity of enzymatically modified isoquercitrin in male or female F344 rats.