Carcinogenesis Bioassay of Agar (CAS No. 9002-18-0) in F344 Rats and B6C3F1 Mice (Feed Study).
A carcinogenesis bioassay of agar isolated from Pterocladia, a gelling agent used in foods and pharmaceuticals, was conducted on groups of 50 F344 rats and 50 B6C3F1 mice of either sex which were fed diets containing 25,000 or 50,000 ppm of the test substance for 103 weeks. Groups of 50 untreated rats and mice of either sex served as controls. Mean body weights of dosed and control male rats were comparable throughout the study. After week 80, mean body weights of dosed female rats were slightly lower than those of the controls. Mean body weights of dosed and control male mice were comparable throughout the study. The mean body weights of dosed female mice were lower than those of the controls at week 20 and remained lower throughout the study. No compound-related effects on survival, feed consumption, clinical signs of toxicity, or tumor incidence were observed. Although the rats of either sex and male mice might have been able to tolerate higher doses, 50,000 ppm was the administered high-dose level since that is the maximum concentration of a test substance in feed recommended in the guidelines of the BioassayProgram. A statistically significant trend (P=0.015) was observed for the increased incidence of cortical adenomas of the adrenal gland (control, 0/50; low-dose, 0/50; high-dose, 4/50) in female rats; the difference between control and high-dose groups was not significant. In male mice the incidence of hepatocellular adenomas (control, 0/49; low-dose, 3/50; high-dose, 7/50) was significantly (P=0.007) increased in the high-dose group when compared with controls; likewise, the overall trend was significant (P=0.005). The incidence of total liver tumors (control, 9/49; low-dose, 8/50; high-dose, 13/50) did not differ significantly among the groups. Neither of these increases (in cortical adenomas or in liver tumors) was considered to be compound related. Under the conditions of this bioassay, the agar isolated from Pterocladia was not carcinogenic for F344 rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative