ABSTRACT
1'-S-1'-acetoxychavicol acetate (ACA) has been previously reported to reduce tumor volume in nude mice, at an effective dose of 1.56â¯mg/kg body weight. However, the detailed toxicological profile for ACA has not yet been performed. Herein, we investigated the toxicity of intravenous administration of ACA in male and female Sprague-Dawley rats, both acutely (with single doses of 2.00, 4.00 and 6.66â¯mg/kg body weight, for 14â¯days), and sub-acutely (with weekly injections of 0.66, 1.33, and 2.22â¯mg/kg, for 28â¯days). In both toxicity studies, treatment with ACA did not affect behavior, food/water intake or body weight, nor did it induce any changes in clinically relevant hematological and biochemical parameters or mortality, suggesting that the LD50 of ACA was higher than 6.66â¯mg/kg body weight, regardless of sex. Sub-acutely, there was however, mild focal inflammation of kidneys and lobular hepatitis, but these were not associated with significant functional adverse effects. Therefore, the no-observed-adverse-effect level (NOAEL) for intravenous administration of ACA in the present 28-day sub-acute study was 2.22â¯mg/kg body weight, in both male and female rats. These findings provide useful information regarding the safety of ACA use in a healthy, non-tumor-bearing rat model.
