Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The substance is not irritating to the rabbit skin or eyes.

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:

A pre-GLP study according to EPA guideline (§ 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978) was performed (Ciba 801995 (1980)). The test item contained 89% active ingredient and 10% urea and was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. Grade 1 edema was noted after 24 and 48 h for some animals with abraded skin only. Erythema could not be assessed due to the coloration by the dye. The test material is not irritating to the rabbit skin.

In support of this study several other studies are available. Firstly, in a study by CIBA-Geigy Ltd.(Ciba 785731 (1979)), according to "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics; US Association of Food and Drug Officials), the test item (which contained 67% active ingredient) was applied at a concentration of 50% in vehicle (propylene glycol and saline, 70:30 parts). Three male and female New Zealand rabbits were shaved on the back. The left side was abraded. Gauze patches of 6.25 cm² were loaded with 0.5 g of the test item. Both the abraded and non abraded sites were treated and covered with an impermeable material for 24 h. The skin irritation was assessed after 1, 2, 3, 4 and 7 days. No erythema and no edema were noted at any observation time.

Secondly, CIBA-Geigy Ltd.(Ciba 875185 (1987)) conducted a study according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion) but not in compliance with GLP. The test item contained 20% active ingredient, 79% water and 1% TEA-HCl buffer. Three male albino rabbits were treated with 0.5 ml in a gauze patch of 20 cm². The patches were covered with aluminium foil and held in place for four hours with adhesive tape. Skin reactions were observed 1, 24, 48 and 72 hours after patch removal. No erythema or edema were noted at any observation time point.

Thirdly, BASF AG 81/115 (1981) performed a study according to J. H. Draize: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. In Dermal Toxicity pp. 46 - 59, 1959. Austin, Tex.: Association of Food and Drug Officials of the United States, Texas, State Department of Health. The study was not performed in compliance with GLP. Three rabbits (1 male and 2 females) were used in this study. The backs of the rabbits were shaved (2.5 x 2.5 cm). Test patches (2.5 x 2.5 cm) were loaded with undiluted test material (containing 14.5% active ingredient, 83% water, 1.5% NPG and 1% salts) and covered with an occlusive dressing. The material was removed by washing 3 minutes and 4 hours after application. No effect was found on edema but unfortunately erythema could not be scored due to red staining by the test substance.

Read across data are available with Analogue substance 1. The first study (Clariant 2002) was performed to assess the irritation of the test material to the skin of the New Zealand White rabbit (SPL Standard Test Method 540.06). The method followed OECD Guidelines for Testing of Chemicals (1992) No. 404 "Acute Dermal lrritation/Corrosion" and Method 84 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). Three New zealand white rabbits were used in the semiocclusive test. The rabbits were exposed to 0.5 g of the test material for four hours. Very slight erythema was noted at two treated skin sites one and 24 hours after patch removal and persisted at one treated skin site at the 48-hour observation. An isolated incident of very slight oedema was noted at one treated skin site one hour after patch removal. No other signs of skin irritation were noted. Orange coloured staining was noted at all treated skin sites throughout the study. The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations Commission Directive 93/21/EEC. No symbol and risk phrase are required.

The second study with Analogue substance 1 (Clariant 2007) also assessed the irritation of the test material to the skin of the New Zealand White rabbit (SPL Standard Test Method 540.10). The method followed OECD Guidelines for Testing of Chemicals (24 April2002) No. 404 "Acute Dermal Irritation/Corrosion" and Method B4 of Commission Directive 2004/73/EC (which constitutes Annex V of Council Directive 671548/EEC). Three New-Zealand white rabbits were used in this semiocclusive test. Rabbits were exposed to 0.5 g of the test substance. No evidence of skin irritation was noted. Red-coloured staining was noted at two treated skin sites one hour after patch removal. The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations Commission Directive 2001/59/EC. No symbol and risk phrase are required.

Eye irritation:

A pre-GLP study according to EPA guideline (§ 163.81-4 "Primary eye irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978) was conducted (Ciba 801994 (1981)). The test item contained 89% active ingredient and 10% urea. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. Only in non-rinsed eyes, redness, chemosis and discharge were observed on the first and second day. These findings were no longer noted on the third day. During the whole observation period, parts of the cornea and sclera were reddish stained. Under the conditions of this experiment the test material was found to cause a minimal irritation when applied to the rabbit eye mucosa and no irritation when the application site was rinsed. Taken together, the test material is considered to be not irritating to the eye.

In support of this conclusion several studies are available. A pre-GLP study (Ciba 785730 (1979)) was performed according to Test for eye irritants described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959), the US Association of Food and Drug Officials (AFDO). The test item contained 67% active ingredient. Three male and female New Zealand rabbits were treated with 0.1 g by insertion into the conjunctival sac of the left eye. The lids were gently closed for a few seconds. In three of the rabbits, the treated eye was flushed with 10 ml of physiological saline after ca. 30 seconds. The eye irritation was assessed after 1, 2, 3, 4 and 7 days. In both rinsed and non-rinsed eyes, redness, chemosis and discharge were observed on the first day. These findings were no longer noted on the second day. No other findings were noted at any observation time. Under the conditions of this study, the substance was not irritating to the eye.

The second supporting study, non-GLP, (Ciba 875184 (1987)) was performed according to OECD TG 405. Three male albino rats were treated with 0.1 mL undiluted test substance (which contained 20% active ingredient). The untreated eye of the same animal served as control. Eye irritation was assessed at 1, 24, 48 and 72 hours after application. The substance induced very slight irritation of the conjunctiva (slight redness at 1 hr and 24 hr, mean score 0.33). The eye reactions observed were fully reversible until the end of the observation period on day 3. Under the conditions of this study, the substance was not irritating to the eye.

The third non-GLP supporting study (Ciba 81/115 (1981)) was performed according to Fed. Reg. 38, No. 187, § 1500.42, p. 27019 of Sept. 27, 1973. Three male and three female Vienna white rabbits were treated with 0.1 mL undiluted test substance (which contained 14.5% active ingredient, 83% water, 1.5% NPG and 1% salts); the untreated eye of the same animal served as control. Eye irritation was assessed at 24, 48 and 72 hours after application. The substance induced slight redness of the conjunctivae at 48 hours in three rabbits and slight corneal opacity in one rabbit at 72 hours (last observation time point). Under the conditions of this study, the substance was not irritating to the eye.

Data on read acros from structure Analogue substance 1 are also available. The first study (Clariant, 2007), for which GLP was not claimed, was performed to assess the irritation of the test material to the eye of the New Zealand White rabbit (SPL Standard Test Method 560.09), The method followed OECD Guidelines for Testing of Chemicals (24 April 2002) No. 405 "Acute Eye Initation/Corrosion" and Method B5 of Commission Directive 2004/73/EC (which constitutes Annex V of Council Directive 67/548/EEC). Three New Zealand white rabbits received a single application of 0.1 mL of undiluted test substance. The test substance produced moderate conjunctival irritation. Dark red-coloured staining of the lower conjunctival and nictitating membranes and red-coloured staining of the fur around the treated eye were also noted. One treated eye appeared normal at the 72-hour observation and the two remaining treated eyes appeared normal at the 7-day observation. Classification: MILD IRRITANT (CLASS 4 ON A 1-8 SCALE). The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC

The second read-across, GLP compliant, study (Clariant, 2002) was performed to assess the irritation of the test material to the eye of the New Zealand White rabbit (SPL Standard Test Method 560.09). The method followed OECD Guidelines for Testing of Chemicals (24 April 2002) No. 405 "Acute Eye Initation/Corrosion" and Method B5 of Commission Directive 2004/73/EC (which constitutes Annex V of Council Directive 67/548/EEC). Three New Zealand white rabbits received a single application of 0.1 mL of undiluted test substance. The test substance produced scattered or diffuse corneal opacity, iridial inflammation and moderate to severe conjunctival initation. All treated eyes appeared normal at the 21-day observation. Classification: AT LEAST A MILD IRRITANT (CLASS 4 ON A 1-8 SCALE). The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 93/21/EEC.

Justification for classification or non-classification

The test substance does not have to be classified for skin and eye irritation to according to Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Categories Display