A bioassay of cinnamyl anthranilate (a synthetic flavoring agent) for possible carcinogenicity was conducted by administering the test chemical in feed to F344 rats and B6C3F1 mice.
Groups of 50 rats and 50 mice of each sex were fed the test chemical in diets containing 15,000 or 30,000 ppm for 103 weeks and then observed for an additional 2 or 3 weeks. Controls consisted of groups of 50 untreated rats and 50 untreated mice of each sex. All surviving animals were killed and necropsied at 105 to 107 weeks.
Mean body weights of the dosed male and female rats and mice were lower than those of the corresponding controls throughout the bioassay, and weight decrements were dose related. Mortality in rats and mice of either sex was not affected by administration of the test chemical.
In male rats, adenocarcinomas or adenomas of the renal cortex and acinar-cell carcinomas or adenomas of the pancreas were found in low incidences in dosed rats but not in control rats. In direct comparisons with matched control groups, the incidences of these tumors were not significantly increased; however, because these tumors rarely occur spontaneously in aging F344 rats, they were considered to be related to compound administration. Similar pancreatic or renal tumors have not been detected among 634 historical-control male F344 rats at the same laboratory.
In the female rats, no tumors occurred at incidences that could be clearly related to the administration of the test chemical.
In both male and female mice, the incidences of hepatocellular carcinomas or adenomas were dose related (P<0.001) and significant (P< 0.001) in direct comparisons of dosed and control groups.
It was concluded that under the conditions of this bioassay cinnamyl anthranilate was carcinogenic for male and female B6C3F1 mice, inducing increased incidences of hepatocellular carcinomas or adenomas. The test chemical was also carcinogenic for male F344 rats, inducing low incidences of acinar-cell carcinomas or adenomas of the pancreas and adenocarcinomas or adenomas of the renal cortex. Cinnamyl anthranilate was not carcinogenic for female F344 rats.