Histopathological evaluation of proliferative liver lesions in rats fed trans-anethole in chronic studies.
In a two-year study of rats fed trans-anethole--a flavouring that is Generally Recognized As Safe by the US Food and Drug Administration--a slight increase in proliferative lesions of the liver was observed. These results were reviewed by a Pathology Working Group (PWG) and their findings are detailed here. The increased incidence of non-neoplastic lesions in male and female rats fed 0.25, 0.5 or 1.0% trans-anethole was considered by the PWG to be treatment related. Male and female rats fed 0.25% trans-anethole in their diet (25 to 29 times the postulated maximum human intake) had no significant treatment-related microscopic lesions in the liver, although there was a slight increase in parenchymal cell hyperplasia. Rats fed 0.5% trans-anethole had hepatic changes consistent with those caused by chronic exposure of rodents to compounds with enzyme-inducing activity. Male and female rats fed 1.0% trans-anethole revealed increased incidence and severity of hepatic changes as seen in the mid-dose rats, and a low incidence of hepatocellular neoplasms. These neoplasms were not increased in male rats in any dietary group or in female rats of the low- (0.25%) and mid-dose (0.5%) groups. The slightly increased incidence of hepatocellular neoplasms in the high-dose females is not considered to be of significance to human safety and it is concluded that trans-anethole does not constitute a carcinogenic risk for man. The slightly increased tumour incidence was seen only in the highest dose group of one sex; it has not been observed in studies of mice fed trans-anethole--the metabolism of trans-anethole in the mouse is similar to that in man. The extremely high exposure was associated with other liver changes which may have contributed to the findings.
Newberne
P M
PM
Department of Pathology, Boston University School of Medicine, MA 002118.
Carlton
W W
WW
Brown
W R
WR
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D005421:Flavoring Agents / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D051381:Rats; D013194:Staining and Labeling
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D005421:Flavoring Agents; C006578:anethole