Registration Dossier

Administrative data

Description of key information

Results of an in vitro skin corrosion/irritation study on the read-across substance  wheat glucose syrup performed according to test guidelines have demonstrated that the compound is not a skin irritant (Höpfner, 2010). 
In accordance with section 1 of REACh (Regulation (EC) No 1907/2006) Annex XI, the in vivo skin irritation study (required in Annex VIII section 8.1.1) is not scientifically necessary as the in vitro EpiSkin study is valid for the classification of substances for skin irritancy according to CLP criteria; further testing on vertebrate animals for skin irritation shall be omitted.
In a GLP-compliant in vitro Bovine Corneal Opacity and Permeability (BCOP) test performed according to test guidelines, the read-across substance “Glucose Syrups Wheat Hydrolized” was considered to be not occular corrosive (Seibersdorf Labor GmbH, 2010).
In a GLP-compliant in vivo Acute Eye Irritation / Corrosion test performed according to test guidelines, the read-across substance “Glucose Syrups Wheat Hydrolized” was considered to be not irritant (Seibersdorf Labor GmbH, 2010).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Metabolic data demonstrate that the notifiable substance (identified under the brand name 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 Lycasin® 80/55, considering their common metabolic products.

 

An in vitro skin corrosion/irritation study on wheat glucose syrup was identified, which was performed according to OECD Guidelines for the Testing of Chemicals 431 (in vitro skin corrosion: human skin model method) and 439 (in vitro skin irritation: reconstructed human epidermis test method) and in compliance with GLP (Höpfner, 2010).

In the skin corrosion study, 25 mg of finely grounded dried wheat glucose syrup with 25 µL of water was applied to the human skin model EpiDerm for 3 minutes and 60 minutes followed by a cell viability test {3-[4,5-dimethyl thiazole 2-yl] 2,5-diphenyl-tetrazoliumbromide (MTT) assay}. The test was performed in duplicate. Deionised water and 8N KOH were used as negative and positive controls, respectively. The positive control showed clear corrosive effects (mean tissue viability of 16.8% after 3-minute of exposure, which was lower than 30%, as required by the assay acceptance criteria). The mean absorbance values were 1.949 after 3-minute and 1.907 after 1-hour of exposure, which was higher than 0.8 as required by the assay acceptance criteria. In addition, the maximum inter tissue viability differences of the test substance treated skin discs were 1.6% for the 3-minute exposure and 6.7% for the 1-hour exposure, which is below 30% as required by the assay acceptance criteria. The relative absorbance values for the test substance were 97.8% after 3-minute exposure and 98.2% after 1-hour exposure, which were above the threshold for corrosion (50%). Therefore, dried wheat glucose syrup is considered as a non-corrosive substance in the in vitro Human Skin Model Test.

In the skin irritation study, 25 mg of finely grounded dried wheat glucose syrup with 25 µL of water was applied to the human skin model EpiDerm for 60 minutes followed by a cell viability test {3-[4,5-dimethyl thiazole 2-yl] 2,5-diphenyl-tetrazoliumbromide (MTT) assay}. The test was performed in triplicate. Deionised water and 5% sodium dodecylsulphate (SDS) solution were used as negative and positive controls, respectively. The positive control showed clear irritating effects (mean tissue viability of 6.1%, which is lower than 20%, as required by the assay acceptance criteria). The absorbance values were within the required acceptability criterion of 1.0<mean optical density (OD)<2.5 and variation among replicates was acceptable for the negative control, positive control and the test item (<18%). The mean relative absorbance value for the test item was 96.9%, which was above the threshold for irritation (50%). Therefore, dried wheat glucose syrup is considered as a non-irritant in the in vitro Human Skin Model Test.

 

In accordance with section 1 of REACh (Regulation (EC) No 1907/2006) Annex XI, the in vivo skin irritation study (required in Annex VIII section 8.1.1) is not scientifically necessary as the in vitro EpiSkin study is valid for the classification of substances for skin irritancy according to CLP criteria; further testing on vertebrate animals for skin irritation shall be omitted.

 

An in vitro eye irritation study on the read-across substance “Glucose Syrups Wheat Hydrolized” was identified, which was performed according to OECD Guideline for the Testing of Chemicals No. 437 and in compliance with GLP (Seibersdorf Labor GmbH, 2010).  In this study, bovine corneas were pre-incubated with Eagle’s minimum essential medium (EMEM) for 1 hour and then exposed to 750 µL of the test substance at a concentration of 20% in deionised water for 4 hours.  Corneas were washed 3 times with EMEM (containing phenol red) and once with EMEM (without phenol red). Observations of opacity and permeability were recorded.  For the purpose of permeability measurement, fluorescein solution was filled into the anterior chambers of the cornea holders followed by an incubation period of 90 minutes. Sterile de-ionized water and 20% imidazole solution were used as the negative and positive controls, respectively.  An in vitro irritancy score (IVIS) was calculated.  Both the negative and positive control results were within the historical control data range.  A mean IVIS of 1.1 was reported for the test substance. Based on the observed results and applying the evaluation criteria, Glucose Syrups Wheat Hydrolized does not cause Category 1 serious eye damage in the Bovine Corneal Opacity and Permeability Test (BCOP test) under the test conditions.  The test method does not yet allow for the evaluation of eye irritation. The result does not determine the irritation potential (Category 2) of the test substance.

 

An in vivo eye irritation study on the read-across substance “Glucose Syrups Wheat Hydrolized” was identified, which was performed according to OECD Guideline for the Testing of Chemicals No. 405 and in compliance with GLP (Seibersdorf Labor GmbH, 2010). In this study, 0.1 mL of “Glucose Syrups Wheat Hydrolized” was instilled into the conjunctival sac of the left eye of each of 3 New Zealand White rabbits. Animals were exposed to the test substance for 24 hours and observed over a 72-hours period. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Examinations of the treated eyes at 24 h, 48 h and 72 h showed no effects on the corneae, irises and conjunctivae. Based on the results of this study, the investigators concluded that “Glucose Syrups Wheat Hydrolized” has no irritant effect on eye.

Justification for classification or non-classification

Skin irritation: According to the in vitro EpiSkin results, the acceptable read-across compound is non-corrosive and non-irritating. According to the Guidance on the Application of the CLP Criteria (ECHA Reference ECHA-09-G-02-EN), the EpiSkin method is valid for the classification of substances for skin irritancy according to CLP criteria. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.2.

 

Eye irritation: According to the in vitro BCOP and in vivo Acute Eye Irritation / Corrosion results, the acceptable read-across compound is non-corrosive and non-irritating