Registration Dossier

Administrative data

Description of key information

The dermal irritant potential of the substance was assessed using:
-2 in vivo acute dermal irritation/corrosion tests performed in rabbits according to OECD 404 guideline and Good Laboratory Practices (Hoechst 1988b and Jones & Guest, 1987)
The substance was found to be irritating to the skin.
The ocular irritant potential of the substance was assessed using:
-An in vivo acute eye irritation/corrosion tests performed in rabbits according to OECD 405 guideline and Good Laboratory Practices (Hoechst 1988c)
The substance was found to be not irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation/corrosion:

Two valid studies were recorded for this endpoint. The Kreiling study (1988) was a reliable without restrictions study and the Jones & Guest study (1987) was reliable with some restrictions due to limited information reported about the tested substance. The Kreiling study (1988) was identified as the key study and supported by the results of the study performed by Jones & Guest (1987).

The Hoechst study (1988b) was performed in rabbits according to the OECD guideline 404 and to the EU Method B.4. The study was conducted in compliance with the principles of Good Laboratory Practice regulations.

Three rabbits were dermally exposed to 0.5 ml of the substance for 4 hours. The test substance was held in contact with the skin by means of a semi- occlusive dressing. Skin reactions were observed approximately 0.5 /1 hour, 24, 48 and 72 hours after removal of the dressing and then on day 7, 14 and 21 in order to observe their reversibility. The mean values of the scores for erythema and oedema were calculated for each animal.

The mean scores over 24, 48 and 72 hours for individual animals were 3.0, 1.3, 2.0 for erythema and 1.0, 1.0, and 0.7 for oedema. No ulceration or necrosis was noted. Erythema and edema had reversed by day 14 and by day 7, respectively.

The Jones & Guest study (1987) was designed to assess the acute dermal irritation of the substance in rabbits according to OECD guideline 404 and in compliance with the principles of Good Laboratory Practice regulations.

The substance was applied to the skin of 3 rabbits and held in contact for 3 minutes, 1 hour and 4 hours by means of a semi-occlusive dressing.

After 3 minutes of exposure, no skin irritation was observed 1 hour after removal of the patch, but a very slight to well defined erythema and a very slight oedema were observed at 24, 48 and 72 hours in all animals. All reactions cleared within 14 days.

After 1hour of exposure, no skin irritation was observed one hour after patch removal in 1 animal while the 2 remaining animals showed very slight erythema and oedema. 24, 48 and 72 hours after patch removal , a well defined to moderate erythema and a very slight oedema were observed in all animals. All reactions cleared within 14 days.

After 4 hour of exposure, very slight erythema was noted for all animals one hour after patch removaland 2 out of 3 animals showed a very slight oedema. 24, 48 and 72 hours after patch removal, a well defined to moderate erythema and a very slight oedema were observed in all animals except for 1 which showed a severe oedema at the 24 -hour reading. At any dose level, all treatment sites showed desquamation on day 7 but were normal on day 14.

Mean scores over 24, 48 and 72 hours for each animal were 2.0, 1.7 and 2.3 for erythema and 1.0, 1.0 and 2.0 for oedema. All reactions cleared within 14 days.

Eye irritation:

One study is recorded for this endpoint and was chosen as a key study (Hoechst, 1988c).

The potential of the substance to induce eye irritation was assessed in 3 rabbits according to the OECD guideline 405 and to the EU method B.5. The study was conducted in compliance with the principles of Good Laboratory Practice regulations.

A single dose of 0.1ml of the test item was instilled into one eye, the other eye was not treated and served as control.The eyes were not rinsed after administration of the test item.

Ocular reactions were observed 1, 24, 48 and 72 hours. The values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were noted for each animal.

Mean scores calculated over 24, 48 and 72 hours for the 3 animals were 0.3 for chemosis, 0.7 for redness of the conjunctiva, 0 for iris lesions and 0 for corneal opacity. Redness and chemosis were fully reversible within 72 hours.


Effects on skin irritation/corrosion: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Skin irritation/corrosion:

Based on the results of the Hoechst (1988b) and Jones & Guest (1987) studies and according to the criteria laid down in EU directive 67/548/EEC, the substance is considered as a skin irritant and is classified Xi, R38. In each of the above mentioned studies, for 2 of the 3 tested animals

individual mean score for erythema over the 24, 48 and 72-hour readings are equal or greater than the cut-off value of 2.

According to the criteria laid down in EC regulation 1272/2008/EC, the substance is not considered as a skin irritant and is not classified.

In each of the above mentioned studies, only 1 of the 3 tested animals has an individual mean score for erythema over the 24, 48 and 72-hour readings equal or greater than the cut-off value of 2.3.

Eye irritation:

Based on the result of the Hoechst study (1988c) and according to the criteria laid down in EC regulation 1272/2008/EC and EU directive 67/548/EEC, the substance is considered as non-irritant when administered by ocular route and is not classified.