Registration Dossier

Administrative data

Description of key information

Non- skin irritant

Eye damage

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:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The potential of the test item to be irritant to the skin was investigated through an in vitro skin irritation study, using a commercial reconstructed human epidermis (RhE) model named EPISKIN™. The study was performed according to the OECD Guideline 439. The test item, as well as controls, were tested for their ability to impair cell viability after an exposure period of 15 minutes followed by a 42 ± 1 hour recovery period. The blank, negative and positive controls gave acceptable results and the study was accepted as valid. After appropriate subtraction, the mean cell viability of the test item treated tissues was 62 %. Based on the tissue viability obtained, the substance is not considered to be a skin irritant.

Eye irritation

The potential of the test material to induce eye irritation was investigated in a human cornea model in an in-vitro study, performed according to the OECD Guideline 492. The test item was applied to a three-dimensional human cornea tissue model in duplicate for an exposure time of 30 minutes. 50 μl of the liquid test item was applied to each tissue. After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution. Demineralised water and methyl acetate were tested concurrently as negative and positive control respectively. The mean tissue viability was found to be 2.5 %. This value is well below the threshold for eye irritation potential (≤ 60 %). Under the conditions of the test system, the test substance is considered as eye irritant or inducing serious eye damage in the EpiOcularTMEye Irritation Test.

In order to distinguish between eye irritant and induing serious eye damage, the substance was further evaluated in-vitro according to the OECD 437. The corneal damage potential of the substance was assessed by quantitative measurements of changes in opacity and permeability in a bovine cornea. The test item was brought onto the cornea of a bovine eye which had been incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured. The test item was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. The calculated IVIS (in vitro irritancy score) was 84.29 which is within the range for classification (according to the classification criteria of OECD 437) of the substance as causing serious eye damage.

Justification for classification or non-classification

Skin irritation

According to the Guidance on the application of CLP criteria (v.5.0), the OECD 439 can reliably distinguish non-classified from classified substances. All four methods of the OECD 439 are valid for the classification of substances for skin irritation according to CLP criteria. Considering the mean tissue viability obtained after the exposure to the substance the substance is not classified for skin irritation, since the tissue viability is above the threshold for classification (60 %).

Eye irritation

According to the Guidance on the application of CLP criteria (v.5.0), the OECD 492 can be used for identifying substances not causing serious eye damage/eye irritation. Based on the tissue viability obtained during the OECD 492 study, the substance can be considered as an eye irritant or inducing eye damage. To distinguish between these two classifications, the substance was further tested in the OECD 437. The IVIS score obtained was above 55, which is the threshold for classifying a substance as one that induces serious eye damage. A substance can be considered as causing serious eye damage (Category 1) based on positive results in the BCOP test (OECD 437). The substance is therefore classified in Category 1- Eye damage (H318)