90-day oral toxicity study of D-tagatose in rats

D-Tagatose is a ketohexose, tastes like sugar and is useful as a low-calori e sweetener, To assess D-tagatose's safety, an oral 90-day toxicity study w as conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15 , and 20%, D-tagatose, One control group (dietary control) received only la b chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At h igher doses, treatment-related effects included transient soft stools in ma le and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained w eight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose -group females at selected intervals compared to dietary control animals. N o significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increa sed relative liver weights were noted in male and female animals from the 1 0, 15, and 20% dose groups compared to the dietary control. No gross pathol ogical findings correlated with these increased liver weights. Minimal hepa tocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded th at histomorphologic changes associated with D-tagatose were restricted hepa tocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the res ult of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. ( C) 1999 Academic Press.