title: Carcinogenesis Bioassay of D-Mannitol (CAS No. 69-65-8) in F344/N Rats and B6C3F1 Mice (Feed Study).
abstract: A carcinogenesis bioassay of D-mannitol (98%-100% pure), a food and drug additive, was conducted by feeding diets containing 25,000 or 50,000 ppm D-mannitol to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 rats and 50 mice of each sex served as controls. Survival and mean body weights of dosed and control male rats and of dosed and control mice of each sex were comparable. Survival of high-dose female rats was significantly higher (P<0.05) than that of the low-dose female rats. However, neither the survival of the low-dose group nor that of the high-dose group was significantly different from that of the controls. Throughout the study, mean body weight gain of dosed female rats was depressed (</=10%) relative to that of controls. Feed consumption by dosed and control rats and mice of each sex was similar. Although the rats and mice of each sex might have been able to tolerate higher doses, a dietary level of 50,000 ppm (5%) is the maximum concentration of a test substance infeed recommended in the guidelines of the Bioassay Program. Dilatation of the gastric fundal gland was observed in the increased incidence in dosed female rats when compared with that of controls (control, 6/50, 12%; low dose, 23/50, 46%; high dose, 23/50, 46%). Retinopathy and cataracts occurred at increased incidences in high-dose male and low- and high-dose female rats. A mild nephrosis, characterized by focal vacuolization of the renal tubular epithelium, was observed in increased incidence in dosed mice of each sex and was considered to be related to administration of D-mannitol (males: control, 15/50, 30%; low dose, 29/50, 58%; high dose, 30/47, 64%; females: control, 1/48, 2%; low dose, 3/48, 6%; high dose, 14/49, 29%). Under the conditions of this bioassay, D-mannitol was not carcinogenic for F344/N rats or B6C3F1 mice of either sex. Levels of Evidence of Carcinogenicity: Male Rats: Negative Female Rats: Negative Male Mice: Negative Female Mice: Negative