CHRONIC TOXICITY AND CARCINOGENICITY STUDY OF ERYTHRITOL IN RATS

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.