Registration Dossier

Administrative data

Description of key information

In a GLP-study according to OECD test guideline 405, the registered substance induced only slight conjunctivae redness and chemosis, so that it is not classified for eye irritation.
In a GLP-study according to OECD test guideline 404 the registered substance did induce slight edema and moderate erythema, which reversed within 14 days. However, the effects were such that according to the CLP regulation the registered substance is not classified as skin irritating. Furthermore, a human patch test did not show signs of irritation.

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

Skin irritation / corrosion

The skin irritant effect of the registered substance was investigated according to the method recommended in the OECD Guideline No. 404, "Acute Dermal Irritation/ Corrosion", 2002, and the Commission directive 2004/73/EC "B.4. Acute Toxicity: Dermal Irritation/Corrosion", 2004.

During an initial test using one female albino rabbit a sequential application (exposure time 3 min, 1 h and 4 h) of the test item was carried out on one site of the left back area each. The skin was examined for signs of irritation straight after as well as 1 h, 24 h, 48 h and 72 h after the termination of exposure. Since the animal did not show any sign of skin irritation within the observation period of 72 hours it was decided to carry out a confirmatory test with two additional animals in order to allow a categorization of the test item based on the classification criteria.

Two female albino rabbits were exposed to the test item at one skin site on the back during the confirmatory test. After 4-hour exposure time the test item was removed and the skin was examined 1 h, 24 h, 48 h and 72 h after the termination of exposure as well as on day 7 and 14. In contrast to the initial test partially uncertain skin reactions were revealed at these animals. A well defined formation of erythema and oedema was only shown on the peripheral area, whereas the treated skin in the centre of the real test area did not show an erythema at first.

On account of these contradictory and uncertain findings it was not possible to assess clearly the effects caused by the test item. That is why a repetition of the experiment was agreed.

During the repetition experiment an exposure time of 4 hours was determined, because the preceded investigation did not indicate corrosive effects. The test item was applied to one skin site of the shaved back of three more female albino rabbits. The skin was cleansed with mild soapsuds after the 4-hour exposure time. In spite of ail this the test item seemed to leave a slight oil film on the skin. The skin was examined for signs of irritation 1 h, 24 h, 48 h and 72 h after the termination of exposure as well as on day 7 and 14. Well defined skin reactions were observed at these three rabbits. But all effects were fully reversible within 14 days. Under the experimental conditions described in this report the mean scores during the repetition experiment after the 4-hour exposure were:

Animal No.                 Erythema                 Oedema

3266                        2.00                       0.33

3268                        2.33                       1.00

3269                        2.00                       0.00

Under the experimental conditions described in this final report, the mean score for erythema was 2.1 and for oedema 0.4.(Cognis 2006).

These results are supported by a repeated human insult patch test, which was completed by 110 participants. In this study the registered substance did not indicate a clinically significant potential for dermal irritation (see section 7.10.5) (CPT, 2007) .

eye irritation / corrosion

The local effect of the registered substance was investigated according to the method recommended in the OECD Guideline No. 405, "Acute Eye Irritation/ Corrosion", April 2002 and the Commission directive 2004/73/EC "B.5. Acute Toxicity: Eye Irritation/ Corrosion", April 2004.

At first only one female albino rabbit was exposed to 0.1 mL of the test item in one eye during an initial test. The eye was examined and the changes were graded according to a numerical scale 1 h, 24 h, 48 h and 72 h after dosing as well as on day 7. Changes ranging from slight to well defined were observed in the treated eye. Based on these findings two more female albino rabbits were treated with 0.1 mL of the test item each. Likewise ocular defects were graded 1 h, 24 h, 48 h and 72 h after dosing. Both of the test animals showed slight changes in the eyes.

All effects were fully reversible within 7 days.

The following mean values, based on the results from the 24-hour-, 48-hour- and 72hour-readings were calculated:

Animal No.

Cornea opacity

Iris lesion

Redness of Conjunctiva

Oedema of Conjunctiva

3116

0.00

0.00

1.33

1.00

3628

0.00

0.00

0.67

0.33

3621

0.00

0.00

0.67

0.33

Based on the individual mean values mentioned above the following mean values were calculated:Cornea opacity 0.00, Iris lesion 0.00, Redness of Conjunctiva 0.9 and Oedema of conjunctiva 0.6. (FREY-TOX, 2006).

Justification for classification or non-classification

Based on the results of the skin and eye irritation key toxicity studies, the test item is not classified according to Directive 67/548/EEC (DSD). No classification is needed according to Regulation (EC) No 1272/2008 (GHS, CLP).