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Description of key information

In a key carcinogenicity study with Malbit® (87% maltitol, 5% sorbitol, 6% maltotriitol, dry substance), the NOAEL for carcinogenicity of 1.5 g/kg body weight/day was derived for male and female rats (Conz, 1992).   
In another carcinogenicity study with Lycasin® (7% sorbitol, 52.5% maltitol, 22.5% hydrogenated tri- to hexasaccharides, 17.5% polysaccharides), the NOAEL value of 18% in drinking water was derived for male and female rats (Leroy and Dupas, 1984).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
1 500 mg/kg bw/day

Justification for classification or non-classification

The carcinogenicity studies available indicate that the notifiable substance does not induce cancer or increase its incidence. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.6.

Additional information

Metabolic data demonstrate that the notifiable substance (Lycasin® 80/55), as well as the read-across substances (maltose, maltitol, sorbitol, wheat glucose syrup (WGS), and dextrin) share a common metabolic pathway as they are converted to D-glucose and/or sorbitol via hydrolysis of their glycosidic linkages by the intestinal brush border carbohydrases. On the basis of their common mono- and disaccharide metabolites, the properties of the notifiable substance, Lycasin® 80/55 is expected to be similar to the read-across substances maltose, sorbitol, maltitol, WGS, and dextrin. Considering this, it is anticipated that exposure to any of the aforementioned saccharides would ultimately result in the formation of D-glucose and/or sorbitol. As such, maltose, sorbitol, maltitol, WGS, and dextrin may be used as appropriate surrogates for the notifiable substance, considering their common metabolic products.


The carcinogenicity of Malbit® (87% maltitol, 5% sorbitol, 6% maltotriitol, dry substance) was evaluated in a 2-year carcinogenicity study in rats (Conz, 1992). This GLP study was similar in design to OECD test guideline 453. Malbit® was administered via the diet at 0 (control), 0.5, 1.5, or 4.5 g/kg body weight/day to Sprague-Dawley rats (50 rats/sex/group) for 2 years. Animals remained untreated until spontaneous death and were then assessed for complete gross necropsy and microscopic examinations. There were no treatment-related effects in mortality, body weight, food consumption, or behaviour. Treatment induced a slight increase of adrenal medullary hyperplasia at all dose levels compared to controls and at the high-dose (4.5 g/kg body weight/day), this change was associated with an increase in frequency of pheochromocytomas; however the change in frequency of adrenal medullary hyperplasia was not dose-related. The authors commented that these effects, mainly caused by a substantial increase in the proportion of the carbohydrate in the food of these rats, are well known indirect effects with this kind of compound and are considered not to have significance in humans (Vogel, 1989). There were no other treatment-related changes in the incidence of abnormalities observed at gross necropsy or histopathology. The study authors did not identify a NOAEL for carcinogenicity; however, based on these findings, a NOAEL for carcinogenicity of 1.5 g/kg body weight/day was identified for male and female rats.


Another carcinogenicity study with Lycasin® (7% sorbitol, 52.5% maltitol, 22.5% hydrogenated tri- to hexasaccharides, 17.5% polysaccharides), which was similar in design to OECD test guideline 451, was identified (Leroy and Dupas, 1984). Lycasin® at 0 (control) or 18% in acidified drinking water was administered to Sprague-Dawley rats (50 rats/sex/group) for 2 years. Endpoints assessed included clinical signs, body weight, food and water consumption, haematology, clinical chemistry, urinalysis, gross pathology, and histopathology. Diarrhoea appeared from the first week and decreased from the fourth week in treated animals. In addition, adaptation to the diet caused considerable caecum hypertrophy (the caecum weight of treated animals has more or less doubled). These observations are usually observed on animals treated with glucide rich diets. Food consumption by rats undergoing Lycasin® 80/55 treatment during the study is about 35% lower (i.e., about 19 g/kg/day) than the amount consumed by control rats. However, the authors commented that treated rats drank more, which resulted in a Lycasin® ingestion of about 18 g/kg/day per animal. Taking into account the average caloric value of the diets used, i.e., 3000 Cal/kg (A03:3200 Cal and A04: 2900 Cal), there is a deficit of about 57 Cal (19 g x 3 Cal) and an excess of about 72 Cal (18 g x 4 Cal) if we consider Lycasin® 80/55 as a glucide. Weight gains in both groups were similar, except a short preliminary period of adaptation. Subsequently, the treated female body weight was nearly always slightly higher than the control females. The treated males body weight which was slightly lower during the first year, increased during the second year to slightly exceed that of the control group. The authors commented that these were due to the fact that Lycasin® has caloric properties which are very close to those of glucides. Haematological examination revealed no difference between the control and the treated groups. Biochemical blood examinations noted a noticeable uremia decrease in both treated males and females, as compared with the control group, after 20.5 and 24 months treatment. The authors noted that this fact can be attributed to a steadily increasing consumption of drinking water (from 12 to 50% for males and from 25 to 60% for females). Macroscopic anatomopathological examinations and organ weight revealed no significant difference except the caecum hypertrophy mentioned above. Microscopic anatomopathological examination revealed that Lycasin® 80/55 administration did not cause more senescence lesions in treated than in control animals and the incidence of tumors (46 in the control group and 43 in treated animals). Based on the results, the authors concluded that Lycasin® 80/55 has no toxic or carcinogenic properties under experimental conditions. The authors commented that the only differences observed between control and treated groups are explained by the kind of Lycasin® 80/55 administration in animals:

-Hyperosmolarity of drinking water

-Higher glucides content in the diet than that normally used by the rat and substantially higher than under practical conditions of Lycasin® 80/55 consumption by humans.

NO(A)EL for carcinogenicity was not reported. Based on the results presented, the NO(A)EL for carcinogenicity was 18% in drinking water for male and female rats.