Subchronic toxicity study of gallic acid by oral administration in F344 rats

Subchronic toxicity of gallic acid (GA) was investigated in F344 rats by fe eding diet containing 0, 0.2, 0.6, 1.7 and 5% GA for 13 weeks. Each group c onsisted of 10 rats of each sex. Toxicological parameters included clinical signs, body weight, food consumption, hematology, blood biochemistry, orga n weights and histopathological assessment. Body weight gain in the 5% GA-t reated animals of both sexes from week 1 to the end of the experiment was s ignificantly lower than that of the untreated controls. Toxic effects follo wing administration of 0.6% or more in males and 5% in females included red uction of hemoglobin concentration, hematocrit and red blood cell counts an d increase in reticulocytes. Histopathologically, extramedullary hematopoie sis, hemosiderin deposition and congestion appeared in the spleens of 5% GA -treated animals, suggesting development of hemolytic anemia. In addition, centrilobular liver cell hypertrophy, reflected in increase in liver weight , was observed in animals of both sexes from 1.7%. In the kidney, Berlin bl ue-negative brown pigment deposition in the proximal tubular epithelium was observed at 5% GA. However, the severity of these pathological changes was weak. Based on the present toxicology data, 0.2% was determined to be a no -observed-adverse-effect level (NOAEL) in rats. This level was translated i nto 119 and 128 mg/kg/day, respectively for male and female rats. (C) 2001 Elsevier Science Ltd. All rights reserved.