The potential toxicity and carcinogenicity of erythritol, a low-calori
e sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Group
s of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythrito
l, or 10% mannitol, for a period of 104-107 weeks. To each of these ma
in groups, two satellite groups of 20 males each were attached for int
erim kills after 52 and 78 weeks of treatment. At start of the study,
the rats were 5-6 weeks old. The average intakes of erythritol in the
2, 5, and 10% groups were 0.9, 2.2, and 4.6 g/kg body wt/day for males
and 1.0, 2.6, and 5.4 g/kg body wt/day for females, respectively. Man
nitol intakes were 4.4 and 5.2 g/kg body wt/day in males and females,
respectively. All treatments were well tolerated without diarrhea or o
ther side effects. Body weights were significantly below control level
s during most of the study in males of the 5% erythritol group and in
males and females of the 10% erythritol and 10% mannitol groups, Survi
val of the animals was not adversely affected by the treatments. Hemat
ological. and clinicochemical examinations did not reveal noticeable c
hanges which could be attributed to treatment. Analysis of urine sampl
es collected during five 48-hr periods, from rats of the satellite gro
ups in Weeks 26, 42, 50, and 78 and from rats of the main groups in We
ek 102, showed that about 60% of ingested erythritol was excreted unch
anged. The urine volumes increased with increasing dietary erythritol
levels. In line with previous observations on other polyols, erythrito
l and mannitol ingestion led to an increased excretion of urinary calc
ium and citrate. The urinary excretions of sodium, potassium, phosphat
e, N-acetylglucosaminidase (NAG), gamma-glutamyltransferase (GGT), low
-molecular-weight protein (LMP), and total protein (TP) were slightly
elevated in the 10% erythritol group. Increased GGT and NAG excretions
also were seen occasionally at the 5% dose. Significantly increased r
elative cecum weights were seen in rats of either sex in the 10% manni
tol and, somewhat less pronounced, 10% erythritol groups. Some cecal e
nlargement also was seen in the 5% erythritol group. The relative weig
ht of the kidneys was highest in the 10% erythritol group, the differe
nce from controls reaching statistical significance at interim bills (
males) and termination (females). Except for more frequent pelvic neph
rocalcinosis in female rats of all erythritol dose groups, the histopa
thological examinations did not reveal any nonneoplastic, preneoplasti
c, or neoplastic changes that could be attributed to the ingestion of
erythritol. In male and female rats of the 10% mannitol group, pelvic
nephrocalcinosis, which in females was associated occasionally with pe
lvic hyperplasia, was the only remarkable finding. The incidence and p
rogression of nephrosis, which is commonly seen in aging rats of this
strain, were not influenced by the treatments. In the absence of morph
ological alterations in the kidneys or other signs of nephrotoxicity,
the increased excretions of NAG, GGT, LMP, and TP are regarded as inno
cuous, functional sequelae of the renal elimination of erythritol. In
conclusion, the toxicological profile of erythritol in rats resembles
that of other polyols in several respects. Except for nephrocalcinosis
, which is commonly seen in polyol-fed rats, no other treatment-relate
d, morphological changes were observed in the kidneys. Evidence for a
tumor-inducing or tumor-promoting effect of erythritol was not seen. (
C) 1996 Academic Press, Inc.