Chronic toxicity/carcinogenicity study of trans-anethole in rats.

A chronic feeding study was carried out in rats with trans-anethole. The test substance was administered in the diet to groups (n = 26-78) of 312 male and 312 female Sprague-Dawley rats at concentrations of 0, 0.25, 0.5 and 1% for 117-121 wk. The average intakes of trans-anethole varied from 105-550 mg/kg body weight/day. No apparent treatment-related reactions were noted. The only effect was a transient retardation of body-weight gain. No excess mortality was caused by the treatment. No abnormalities related to treatment were seen on necropsy except for reduced adiposity in the highest dose groups. Haematological assessments did not reveal any changes related to treatment. Histological examination revealed certain non-neoplastic and neoplastic lesions common in older rats. The incidence of some hepatic lesions was significantly higher in some treated groups than in controls: altered cell foci (females of the 1% group), nodular hyperplasia (males of the 0.5% group and males and females of the 1% groups), benign tumours (females of the 1% group) and malignant tumours (females of the 1% group). The results are compared with those of previous investigations. The authors of this study stress that the low incidence of hepatocarcinomas is restricted to a single species and sex and to the highest dose tested. This pattern of species, sex and dose dependency strongly suggests that metabolic and pharmacokinetic studies will be helpful in interpreting the significance of the rat tumours with regard to the safe consumption of trans-anethole by man. The changes observed in this chronic feeding study are not thought to be of genetic origin and consequently trans-anethole does not constitute a significant carcinogenic risk to man. Further studies are in progress to substantiate this conclusion.