Registration Dossier

Administrative data

Description of key information

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)

Additional information

No in vivo skin irritation study was performed in accordance to REACH Annex VIII, 8.1.1. Column 2 (the substance is classified as a skin irritant).

An in vitro study according to OECD TG 431 for predicting the non specific, corrosive potential of substances is available. In this study undiluted test item was applied topically on a reconstructed human skin (50 µL; epiCS, CellSystems, Germany). After an exposure period of 3 minutes at room temperature or 60 minutes in an incubator (37 °C, 5 % CO2, maximum humidity), the cell viability was 77 % and 69 %, respectively, as measured by a MTT conversion assay. It was therefore concluded that the test substance is not corrosive to the skin.

Further available is an in vitro skin irritation test according to OECD TG 439. In this study undiluted test item was applied topically on a reconstructed human epidermis (30 µL; epiCS, CellSystems, Germany). After an exposure period of 20 min. at room temperature and a post-exposure incubation of 42 hours in an incubator (37 °C, 5 % CO2, maximum humidity) the cell viability was 2 % as measured by a MTT conversion assay. Thus, the test substance was considered to have an irritant property to the skin.

 

No in vivo eye irritation study was performed in accordance to REACH Annex VIII, 8.1.1. Column 2 (the substance is classified as irritating to eyes with risk of serious damage to eyes).

Three in vitro assays were performed to allow a solid assessment on eye irritant/corrosive properties of the substance.

First, the test substance was investigated in the Bovine Corneal Opacity and Permeability (BCOP) test according to OECD TG 437. This in vitro test method is used to identify chemicals inducing severe eye damage. The epithelial surface of the cornea was exposed to 750 µL of the unchanged test substance. Measurement of corneal opacity and permeability after a 10 minutes exposure time and a 2 hours incubation time revealed an in vitro irritation score (IVIS) well below the value of 55, that would be the threshold for classification of serious eye damage. The positive (1 % sodium hydroxide solution) and negative (water) controls confirmed the validity of the test. Thus, under the conditions of this test no property for severe eye damage was concluded.

Second, an in vitro study for assessing ocular irritation was conducted in a human corneal epithelial (HCE) cell model. This model is recognized in the scientific community as a highly valuable model for the identification of substances that do not require classification for serious eye damage/eye irritancy (e.g. Cotovio et al., Toxicol. in Vitro, 24, 2010, 523 -537), and is routinely used by cosmetic and pharmaceutical companies. Undiluted test item (30 µL) was applied topically to the reconstructed HCE tissue. After an exposure period of 60 minutes (room temperature), followed by a 16 hours post-treatment incubation period (37 °C, 5 % CO2, maximum humidity), the cell viability was 0.4 % as measured by a MTT conversion assay. As the cut-off for a non-irritant to the eye is 50 %, the test substance requires classification for eye irritation/corrosion based on this assay.

Third, the HET-CAM (Hen's Egg Test on the Chorioallantoic Membrane) was conducted according to a protocol of the ICCVAM Test Method Evaluation Report 2010 in order to assess the severe eye damaging potential of the substance. In this test eight days-incubated fertile hen eggs were opened and 300 µL of the test substance was applied onto the chorioallantoic membrane. The effects occuring during the first 300 seconds after application were measured and used to calculate the irritation score. Based on this irritation score (13 of maximal 21) the test item was identified as "severe irritant" to the chorioallantoic membrane.

Based on the weight of evidences and despite the negative BCOP-result, the overall outcome of the in vitro studies for eye irritation leads to the conclusion that the substance has an eye damaging property.


Justification for selection of skin irritation / corrosion endpoint:
The in vitro skin corrosion study is selected, as it indicates no corrosive potential to the skin. However, the substance is classified for its irritant potential to the skin.

Justification for selection of eye irritation endpoint:
The BCOP study is selected, as it is a validated study type and has reliability 1 (without restriction). It indicates no eye damaging property for the substance. However, based on the weight of evidences from the available in vitro studies the substance is classified as Eye Dam. 1.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008, Annex I, classification is warranted as Skin Irrit. 2.

According to Regulation (EC) No 1272/2008, Annex I, classification is warranted as Eye Dam. 1.

According to Regulation (EC) No 1272/2008, Annex I, 3.8.3.4.5, classification as STOT SE 3 is appropriate, since a component of the substance of approx. 15 % (2,2 -bis(4 -hydroxyphenyl)propane, BPA; CAS No 80 -05 -7) is classified as STOT SE 3. Additionally, the available acute inhalation study of the substance gives indications for a respiratory irritant effect (e.g. respiratory distress, serous nasal discharge, nose/muzzle red encrusted), and the classification on skin/eye irritation/corrosion further support this conclusion.