Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Metabolic data demonstrate that the submission substance, 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 submission substance, 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 afore mentioned 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 submission substance, considering their common metabolic products.

 

In a key, non-GLP compliant, bacterial reverse mutation assay (equivalent to OECD guideline 471), Lycasin 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 key, non-GLP mammalian chromosome aberration test (equivalent to OECD guideline 473), Lycasin was administered to Chinese Hamster Ovary (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) (Farrow, 1982). The test article did not induce cytotoxicity or chromosome damage at any concentration and incubations with the positive control compounds (ethylmethane sulfonate and cyclophosphamide in the absence and presence of S9, respectively) 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 key, non-GLP mammalian gene mutation assay (equivalent to OECD guideline 476) was conducted with Lycasin (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.  

 

In a key, non-GLP in vivo micronucleus test (equivalent to OECD guideline 474), male Swiss Carworth Farm Lane-Petter mice were administered Lycasin 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.


Short description of key information:
The genetic toxicity of Lycasin has been assessed in 3 in vitro studies and an in vivo mouse micronucleus study. 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.