Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
18 000 mg/kg bw/day
Additional information

Metabolic data demonstrate that the notifiable substance [wheat glucose syrup (WGS)], as well as the read-across substances (maltose, maltitol, sorbitol, Lycasin® 80/55, 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, WGS is expected to be similar to the read-across substances maltose, sorbitol, maltitol, Lycasin® 80/55, 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, Lycasin® 80/55, and dextrin may be used as appropriate surrogates for WGS, considering their common metabolic products.

 

In a 3-generation non-GLP reproductive toxicity study, male and female Sprague-Dawley rats were orally administered Lycasin 80/55 via the drinking water at concentrations of 0 (control) or 18% , corresponding to approximately 0 or 18 g/kg body weight/day (equivalent to OECD test guideline 416) (Modderman, 1993). Treatment of F1 animals began 12 weeks prior to mating and from birth for subsequent generations until Day 21 of lactation or until week 11 for the F3 generation (further mating details were not reported). No significant changes were noted in either the parental or subsequent generations in any parameter examined (e.g., body weight, food consumption, reproductive performance, pup viability, etc.) and, therefore, the reproductive no-observed-effect level was 18% in the drinking water. 


Short description of key information:
A 3-generation, non-GLP, weight of evidence study in Sprague-Dawley rats with the read-across substance, Lycasin 80/55, demonstrated no toxic or reproductive effects when administered in the drinking water at 18%, the only dose level tested.

Effects on developmental toxicity

Description of key information
Developmental toxicity/teratogenicity studies conducted with the read-across substances sorbitol and Lycasin 80/55 in mice, rats, and hamsters did not demonstrate any toxicity either in the parents or in the offspring.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
1 200 mg/kg bw/day
Additional information

Metabolic data demonstrate that the notifiable substance [wheat glucose syrup (WGS)], as well as the read-across substances (maltose, maltitol, sorbitol, Lycasin® 80/55, 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, WGS is expected to be similar to the read-across substances maltose, sorbitol, maltitol, Lycasin® 80/55, 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, Lycasin® 80/55, and dextrin may be used as appropriate surrogates for WGS, considering their common metabolic products.

 

Weight of evidence, non-GLP, developmental toxicity/teratogenicity studies (equivalent to OECD test guideline 414) were conducted in male and female CD-1 mice, Wistar or Sprague-Dawley rats, and Golden hamsters (Morgareidge, 1972; Modderman, 1993). The animals received either sorbitol (mice, Wistar rats, and hamsters) or Lycasin 80/55 (Sprague-Dawley rats) via oral (gavage) in the following regimen:

(a) Mice: 0 (control), 16, 74, 350, or 1,600 mg/kg body weight/day from Days 6 to 15 of gestation

(b) Rats: 0 (control), 16, 74, 350, or 1,600 mg/kg body weight/day from Days 6 to 15 of gestation (Wistar) or 0 (control), 3,000, 5,000, or 7,000 mg/kg body weight/day from Days 6 to 15 of gestation (Sprague-Dawley); and

(c) Hamsters: 0 (control), 12, 56, 260, or 1,200 mg/kg body weight/day from Days 6 to 10 of gestation.

Maternal and offspring evaluations were unremarkable in all species; no significant changes were noted in any of the following parameters: daily observations, body weights, food and water consumption, ovary and uterine content, external offspring examinations, soft tissue examinations, skeletal examinations, and head examinations. In each study, the NOEL was the highest dose examined; the lowest of these (1,200 mg/kg body weight/day for hamsters) is carried forward for risk assessment purposes.

Justification for classification or non-classification

The reproductive and developmental studies available indicate that the notifiable substance does not adversely affect sexual function and fertility in adult males and females or have effects via lactation, as wells as not affecting development in the offspring.

As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.7.