Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Eye irritant

Skin irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation potential of the substance is evaluated in a weight of evidence approach by using experimental data from the target substance and the similar substance. Two in vitro studies were performed.

The potential of the substance to evoke skin irritation was evaluated in vitro in a reconstructed human epidermis (RhE) test method conducted according to the OECD Guideline 439 and EU Method B.46. The human reconstructed epidermis model was topically exposed for 60 minutes to the neat test item, followed by a cell viability test. Cell viability was measured by dehydrogenase conversion of MTT, into a blue formazan salt that is quantitatively measured after extraction from tissues. The percentage reduction of cell viability in comparison of untreated negative controls was used to predict the skin irritation potential. Sodium dodecyl sulphate was tested as a positive control. All validity criteria were met. Three experiments were performed. The result of the first test run was equivocal, because two of the three replicates of the test item were below the threshold of 50 % and one replicate was above 50 %; the test item showed skin irritation potential. As the result was equivocal, a second test run was performed. The result of the second test run was equivocal, too, because two of the three replicates of the test item were below the threshold of 50 % and one replicate was above 50 %; the test item showed no skin irritation potential. As the result was equivocal, a third and final test run was performed. The result of the third test run was unequivocal and the test item showed skin irritation potential. The three test runs together lead to the final classification that the test item has at least skin irritation potential. After the treatment, the mean value of relative tissue viability was reduced to 37.1 % (1st experiment), 50.5 % (2nd experiment) and 28.9 % (3rd experiment). Two of the three results are below the threshold for skin irritation potential (50 %). The test substance is considered at least skin irritant.

Based on the results of the OECD Guideline 439, the substance is considered at least a skin irritant and no categorisation in Cat.1 or Cat.2 is possible. For this reason, data on Similar Substance 01 is used (Justification for Read Across is given in Section 13). A cross validated prediction of the acute dermal irritation hazard of the similar substance was provided. A 64 % probability of Acute Dermal Irritation non-hazard and consequently a 36 % probability of Acute Dermal Irritation hazard are estimated.

Considering also the data on similar substance, the skin corossion potential of the substance can be excluded and the substance is considered as a skin irritant.

Eye irritation

A weight of evidence approach is followed for the evaluation of the eye irritation potential of the substance.

The potential of the test item to evoke eye irritation was evaluated in the RhCE model in an in vitro study 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 28 minutes. 50 µl of the liquid test was applied to two tissue replicates. 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 was used as negative control and methyl acetate was used as positive control. All validity criteria were met. After treatment with the test item, the mean value of relative tissue viability was 31.0 %. This value is well below the threshold for eye hazard potential (≤ 60 %). Under the conditions of the test, the substance is considered either eye irritant or inducing serious eye damage in the EpiOcularTMEye Irritation Test.

Further data on the eye irritation potential is obtained from the study conducted on the substance according to the OECD Guideline 437 and EU Method B.47. 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 previously had been incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been determined. 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 test item was tested neat. HBSS was used as negative control. The negative control showed no irritating effect on the cornea and the calculated IVIS is 1.34. DMF was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated IVIS is 120.36. The negative control (HBSS) and the positive control (undiluted dimethylformamide) have met the validity criteria. Under the conditions of this test, the test item showed effects on the cornea of the bovine eye. The calculated IVIS is 25.45. According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, cannot be classified in an UN GHS Category with the BCOP test only. In this case no prediction can be made.

Considering the data derived from both studies, the substance cannot be considered as causing serious eye damage but is considered as an eye irritant.

Justification for classification or non-classification

Skin irritation

The tissue viabilities obtained in the three experiments conducted as per the OECD 439 are 37.1 % (1st experiment), 50.5 % (2nd experiment) and 28.9 % (3rd experiment). Two of the three results are below the threshold for skin irritation potential (50 %). The test substance is therefore considered at least skin irritant. To exclude the skin corrosion potential of the substance predicted data on a Similar Substance were considered. Taking into account the available data, the substance is classified as a Skin Irritant (H315), Cat.2 as per the CLP Regulation (EC) No. 1272/2008.

Eye irritation

Based on the tissue viability (31.0 %) determined in the study conducted according to the OECD Guideline 492 the substance is classified as a Cat.1 or Cat.2. Considering the results of the study conducted according to the OECD Guideline 437, no prediction can be made as the IVIS is between 3 -55. From the results of the OECD 437 study, an eye damage potential of the substance can be excluded since the IVIS is not higher than 55. Taking into account both studies, the substance is classified as an Eye Irritant (H319), Cat.2 as per the CLP Regulation (EC) No. 1272/2008.

Categories Display