Six-month toxicity study of oral administration of D-003 in Sprague Dawley rats.

Background: D-003 is a mixture of high molecular weight aliphatic primary acids purified from sugarcane wax (Saccharum officinarum) having cholesterol-lowering and antiplatelet effects.

Aim: This study was undertaken to investigate the toxicity induced by long-term oral administration of D-003 for 6 months to Sprague Dawley rats of both sexes.

Methods: Rats were randomly divided into four groups (20 rats of each sex/group): a control group. which received the vehicle, and three treatment groups, which received oral D-003 at doses of 250, 500 and 1000 mg/kg/day, respectively. Daily clinical observations and control of bodyweight and food consumption were conducted throughout the study period. On completion of active treatment, animals were sacrificed. Pharmacological effects associated with D-003 such as inhibition of platelet aggregation and increase in bleeding time were assessed in two satellite groups (14 animals of each sex/group): a control group and a group treated with the highest dose of D-003. Assessments of platelet aggregation to collagen were performed at baseline and at 6 months, and assessments of bleeding time were done at baseline, after 3 and 6 months of treatment, and after 30 days' washout.

Results: As expected, D-003 significantly inhibited platelet aggregation. Bleeding time was increased after 3 months of treatment with D-003; this increase was maintained at 6 months, and was reversible after washout. Coagulation factors such as prothrombin time and kaolin-activated thromboplastin-time, which were determined in eight male animals from each group, were unaffected by D-003. Data analyses of bodyweight gain, food consumption, clinical observations, blood biochemistry, haematology, organ weight ratios and histopathological findings did not show trends related to D-003 dose or significant differences between control and treated groups.

Conclusion: It was concluded that the highest studied dose of D-003 (1,000 mg/kg/day) represented a non-toxic dose level in the present chronic toxicity study in rats.