Erythritol is a sugar alcohol (polyol) with potential applications as
a low-calorie, bulk sweetener. Ingested erythritol is efficiently abso
rbed and excreted unchanged via the urine since it is not metabolized
systemically by the animal or human body. Erythritol was administered
to four groups of 10 male and 10 female Swiss CD-1 mice and four group
s of 15 male Wistar Crl:(WI) WU BR rats at dietary levels of 0, 5, 10,
or 20% for 90 days. A fifth group of rats received a diet containing
20% erythritol on a time-restricted basis (6 hr/day), and a sixth grou
p received a diet containing 20% mannitol for comparison. There were n
o treatment-related mortalities in either mice or rats. Soft stools an
d occasional diarrhea were observed in rats fed diets with 20% erythri
tol or mannitol but not in mice. Body weights were slightly yet signif
icantly reduced in rats fed 20% erythritol or mannitol and in male mic
e of the 20% dose group. Erythritol intake in the high-dose group was
approximately 12 g/kg body wt in rats and 44 and 45 g/kg body wt in ma
le and female mice, respectively. Hematological and clinicochemical ex
aminations of blood and plasma did not reveal any treatment-related ef
fects. Urine output increased with increasing erythritol dose. In male
and female mice of the 20% erythritol group, the creatinine-normalize
d urinary excretion of protein, K-glutamyltransferase (GGT), and elect
rolytes (Na+, K+, Ca2+, P-i, citrate) was significantly increased whil
e urinary N-acetylglucosaminidase (NAG) remained unchanged. At the 10%
level, significantly increased urinary protein (both sexes) and GGT (
males only) excretion were seen. In rats, the creatinine-normalized ur
inary excretion of GGT, NAG, and some electrolytes (Na+, K+, and Ca2+)
was increased in some erythritol groups but a clear dose-response rel
ationship was evident only for calcium. On termination of the study, c
ecal enlargement was seen in rats of the 10 and 20% dose groups and in
mice of the 20% dose group. Increased relative and absolute kidney we
ights were observed in both sexes of mice in the 20% erythritol group,
in male mice of the 5 and 10% groups, and in rats of the 10 and 20% e
rythritol groups. Histopathological examination did not reveal any tre
atment-related abnormalities in either mice or rats. In conclusion, th
e ingestion of erythritol for 90 days at dietary levels of up to 20% d
id not produce signs of toxicity in mice or rats. In particular, the m
orphological integrity of the kidneys was not adversely affected by th
e treatment in either species. The increases in urinary excretion of p
rotein, GGT, NAG, and electrolytes were considered to result from exte
nsive osmotic diuresis and a potential overload of the renal excretory
system at the high dose levels employed. (C) 1996 Academic Press, Inc
.