Registration Dossier

Administrative data

Description of key information

- skin: not irritating (rabbit: Ciba Geigy Ltd. 1986, IFREB 1978 / 1973)
- eye: not irritating (rabbit: Ciba Geigy Ltd. 1986, BASF AG 1988, IFREB 1978)

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)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

In a dermal irritation study according to GLP and OECD 404 (Ciba Geigy Ltd. 1986; reliability score 1), New Zealand White rabbits (3 animals) were dermally exposed to the test substance (moistened with distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate) for 4 hours under occlusive conditions. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. One animal showed neither erythema nor edema. Very slight edema was seen (score 1) in the other 2 animals at the 1 hour observation. The effect was fully reversible by the 24 hour observation. Therefore, regarding the mean values of the recordings 24 to 72 hours (0, 0.33, and 0.33 for animal 1, 2, and 3, respectively) the test substance is not irritating to the skin.

Additionally, there are two studies of IFREB (1978 and 1973, both: reliability score 2) which were conducted in principle similar to OECD 404.

In the first dermal irritation study (IFREB 1978) the shaved skin of six New Zealand White rabbits was dermally exposed to 0.5 g of the test substance (made to a paste using 0.7 mL of water) for 24 hours under occlusive conditions. A formulation containing approx. 87% of the test substance was applied and not the pure test substance. One flank of the test animals was scarified before treatment while the other flank was left intact. With respect to todays generally accepted standards for testing for skin irritation/corrosion, values from scarified skin are irrelevant for the final judgement of skin irritation potential of the test substance. Animals then were observed 24, 72 h and 7 days after application. Irritation was scored according to the method of Draize. The mean erythema score (24 – 72 h), for each of the six animals was 0.5 (5 animals) or 1 (1 animal). The effects were reversible within 72 h (in 3 animals) or 7 days (in 3 animals). Slight desquamation on day 7 was seen in 2 animals. No edema was found.

The second study of IFREB (1973) was conducted as described above in the first study of IFREB. 0.5 g of the test substance (made to a paste using 0.4 mL of water) was dermally exposed for 24 hours under occlusive conditions. A formulation containing approx. 86% of the test substance was applied and not the pure test substance. The blue colour of the test substance made the macroscopic examination of the erythema impossible. For this reason, skin effects were scored 1 h after removal of the test patch. One hour after removal of the patch (= 25 hours after start of application), examination was till impaired in all animals. 72 hours after application, examinations could not be performed for one animal. No erythema was seen in the other 5 animals 72 h after administration. Additionally, edema was not seen 25 and 72 h after administration in all animals.

These results confirmed that the test substance is not irritating to the skin.

Eye irritation:

In a primary eye irritation study according to GLP and OECD 405 (Ciba Geigy Ltd. 1986; reliability score 2), 70 mg of the unchanged test substance (corresponding to ca 0.1 mL bulk volume) was instilled into the conjunctival sac of the eye of each of three New Zealand White rabbits (without washing). There was no data on purity of the test substance. Animals then were observed for 10 days. Readings were performed at 1, 24, 48 and 72 hours after application. Irritation was scored according to the method of Draize. At the 1 hour observation, well scattered / diffuse areas of opacity (score = 2) was evident in the treated eye of one animal only. The effect was fully reversible by the 24 hour observation. No iritis was observed. Conjunctival redness (mean of 24 - 48 - 72 h was 1.3 in 2 animals and 1 in the third animal) was observed with fully reversibility within 7 (1 animal) or 10 days (2 animals). Additionally, chemosis was noticed (mean of 24 - 48 - 72 h was 1 in 1 animal and 0.33 in the other 2 animals) and was reversible within 48 h (in 2 animals) or 72 h (in 1 animal).

Additionally, there are two studies (BASF AG 1988, reliability score 2; IFREB 1978, reliability score 1) which confirmed the results of the first study.

In the BASF study which was conducted according to OECD 405, 15 mg of the pulverised test substance (corresponding to ca. 0.1 mL bulk volume) was instilled into the conjunctival sac of the eye of each of three Vienna White rabbits (without washing). There was no data on purity of the test substance. Animals then were observed for 72 h. Readings were performed at 1, 24, 48 and 72 hours after application. Irritation was scored according to OECD scoring method. No corneal opacity, iritis or chemosis were observed. At the 1 hour observation, well defined conjunctival redness (score = 2) was evident in the eyes of all animals. The effect was fully reversible by the 24 hour observation. At the 1 hour observation, clearly increased discharge (score = 2) was evident in the eyes of all animals. Also this effect was fully reversible by the 24 hour observation.

In the IFREB study which was conducted similar to OECD 405, 100 mg of a formulation containing approx. 87% of the test substance was instilled into the conjunctival sac of the eye of each of six New Zealand White rabbits (without washing). Animals then were observed for 7 days. Readings were performed at 1 and 24 hours, 2 days, 3 days, 4 days and 7 days after administration. Irritation was scored according to OECD scoring method. Corneal opacity (mean of 6 animals (24 - 48 - 72 h): 0.4), iritis (mean of 6 animals (24 - 48 - 72 h): 0.6), conjunctival redness (mean of 6 animals (24 - 48 - 72 h): 0.72) and chemosis (mean of 6 animals (24 - 48 - 72 h): 1.4) were observed with fully reversibility within 7 days. Discharge was seen in the eyes of all animals up to 24 hours after application. This effect was completely reversible in all animals by the 48 hour observation period.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin and eye irritation under Directive 67/548/EEC.

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008:

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No. 1272/2008.