Registration Dossier

Administrative data

Key value for chemical safety assessment

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 key, non-GLP compliant, bacterial reverse mutation assay (equivalent to OECD guideline 471), Lycasin 80/55 was tested at doses of 0,0.01, 0.05, 0.1, 0.5, and 1 mL per petri dish in Salmonella typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 both in the absence and presence of exogenous metabolic activation [rat liver S9 (induced by Aroclor 1254)] (Fouillet et al., 1978).  The experiment was conducted in triplicate.  Negative (tested without test substance) and positive controls were included in all incubations.  No increases in the reverse mutation rate were noted in any strain either in the absence or presence of metabolic activation.  The authors did not comment on cytotoxicity. Incubation with positive control substances in the absence or presence of metabolic activation resulted in anticipated increases in reverse mutation rates.

 

In a non-GLP mammalian chromosome aberration test (equivalent to OECD guideline 473), Lycasin 80/85, tested in CHO cells at dose levels of 0 (control), 49, 164, 490, 1,640, or 4,900 µg/mL both in the absence and presence of exogenous metabolic activation (S9; details not provided), did not induce cytotoxicity or chromosome damage at any concentration (Farrow, 1982). Additionally, incubations with the positive control compounds (ethylmethane sulfonate and cyclophosphamide) were reported to result in anticipated increases in chromatid damage. As only 100 metaphase cells were evaluated (rather than the 200 required by the OECD guideline), this study is considered to be reliable with restriction.

 

A final non-GLP mammalian gene mutation assay (equivalent to OECD guideline 476) was conducted with Lycasin 80/85 (Farrow, 1982). When tested at levels of 0 (control), 27, 41, 61, 91, 135, 202, 301, 449, 670, or 1,000 µg/mL in L5178Y cells both in the absence and presence of exogenous metabolic activation (S9; details not provided), no cytotoxicity and no increases in the mutant frequency were noted at any concentration either in the absence or presence of metabolic activation. Additionally, incubation with the positive control substances ethylmethane sulfonate and 3-methyl cholanthrene in the absence or presence of metabolic activation, respectively, resulted in anticipated increases in the mutation frequencies (no details on cytotoxicity were provided). This study was deemed to be reliable with restrictions [JC1].

 

In a non-GLP in vivo micronucleus test (equivalent to OECD guideline 474), male Swiss Carworth Farm Lane-Petter mice were administered Lycasin 80/85 at doses of 0 (control), 5, or 25 mL/kg body weight once/day for 2 days via the oral (gavage) route (Siou, 1981). Following sacrifice of the animals 6 hours after the final dose was administered and subsequent examination of the bone marrow, the study authors reported no evidence of mutagenic potential or bone marrow cell toxicity at any concentration whereas an increase in the frequency of micronucleated polychromatic erythrocytes and a decrease in the ratio of polychromatic to normochromatic erythrocytes was reported for animals receiving the positive control compound, urethane. The only death reported was in one male of the high-dose group.

 

In a non-GLP in vivo bone marrow chromosome aberration test (equivalent to OECD guideline 475), male Sprague-Dawley rats were administered sorbitol via the oral (gavage) route at dose levels of 0 (control), 30, 2,500, or 5,000 mg/kg body weight/day once or daily for 5 days (Maxwell and Newell, 1972). No toxicity was observed in any animal and no chromosome damage was noted at any sorbitol concentration whereas chromosome damage was noted in rats receiving the positive control compound, triethylenemelamine. The scoring of less than 200 metaphases in the control group deemed this study to be reliable with restrictions.

 

In a non-GLP dominant lethal assay (equivalent to OECD guideline 478), male Sprague-Dawley rats were administered sorbitol via the oral (gavage) route at dose levels of 0 (control), 30, 2,500, or 5,000 mg/kg body weight/day for either 1 (acute) or 5 (subacute) days (Maxwell and Newell, 1972). Following a post-exposure period of 7 to 8 weeks, the males were mated with virgin rats of the same strain. No toxicity was observed in any animal and no dominant lethal findings (i.e., changes in the numbers of live and dead implants, changes in post-implantation loss, differences in pup sex, etc.) were noted at any sorbitol concentration (dominant lethal findings were noted in rats receiving the positive control compound, triethylenemelamine). The study was deemed to be reliable with restrictions based on the following deviations: the use of fewer than 30 females per dose level and the lack of positive or vehicle control in the subacute test.



Short description of key information:
The genetic toxicity of wheat glucose syrup has been assessed using the read-across substances Lycasin 80/85 and sorbitol in three in vitro studies (including 1 bacterial reverse mutation test, 1 mammalian gene mutation assays, and 1 chromosome aberration assays) and three in vivo studies. All the genetic toxicity studies are classified as “weight of evidence.” All results are negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The notifiable substance produced negative results in both in vitro and in vivo genetic toxicity studies. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.5.