Registration Dossier

Administrative data

Description of key information

The substance was not irritating or corrosive to the skin in a GLP-compliant OECD 439 and 431 study.

The substance was not irritating to the eyes in a GLP-compliant OECD 437 study.

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

The ability of the test substance to induce induce skin irritation on a human three dimensional epidermal model (EPISKIN Small model (EPISKIN-SMTM)) was evaluated in a GLP compliant study according to OECD 439 and EU B.46. The possible skin irritation potential of the test item was tested through topical application for 15 minutes. The test item was applied undiluted (25 μL), directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42 hour postincubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with the test item compared to the negative control tissues was 85%. Since the mean relative tissue viability for the test item was above 50% after 15 ± 0.5 minutes treatment the test item is considered to be non-irritant. The positive control had a mean cell viability of 16% after 15 ± 0.5 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 12%, indicating that the test system functioned properly. In conclusion, the test substance is non-irritant in the in vitro skin irritation test under the experimental conditions described.

The ability of the test substance to induce skin corrosion was evaluated in a GLP compliant study according to OECD 431 and EU B.40bis, using a human three dimensional epidermal model (EpiDerm (EPI-200)). The possible corrosive potential of the test substance was tested through topical application for 3 minutes and 1 hour. The test item was applied undiluted (50 μL) directly on top of the skin tissue. The positive control had a mean relative tissue viability of 6% after the 1-hour exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the acceptance limits of OECD 431 (lower acceptance limit ≥0.8 and upper acceptance limit ≤ 2.8) and the laboratory historical control data range. In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was ≤ 14%, indicating that the test system functioned properly. Skin corrosion is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with the test item compared to the negative control tissues was 78% and 85%, respectively. Because the mean relative tissue viability for the test item was not below 50% after the 3-minute treatment and not below 15% after the 1-hour treatment the test item is considered to be not corrosive. In conclusion, the test substrate is not corrosive in the in vitro skin corrosion test under the experimental conditions described.

Eye irritation

The eye hazard potential of the test substance was measured by its ability to induce opacity and increase permeability in an isolated bovine cornea in a GLP compliant study according to OECD 437. The eye damage of the test substance was tested through topical application for 10 minutes. The test item was applied as it is (750 μL) directly on top of the corneas. The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (Ethanol) was 64 and was within two standard deviations of the current historical positive control mean. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. The test item did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -2.1 after 10 minutes of treatment. In conclusion, since the test substance induced an IVIS ≤ 3, no classification is required for eye irritation or serious eye damage.

Justification for classification or non-classification

Based on the available information classification for skin or eye irritation is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.