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EC number: 939-581-9 | CAS number: -
Skin irritation:Weight-of-evidence approach using 6 in vivo skin irritation studies performed according to OECD guideline 404.
Eye irritation: Weight-of-evidence approach using 10 studies performed according to or similar to OECD guideline 405.
The degree of primary dermal irritation caused by the test item was determined after application to the shaven skin of 3 rabbits. The study was carried out according to OECD guideline 404 and EU method B.4. Initially one animal was used, and 3 semiocclusive patches were applied sequentially during 3 minutes, 1 and 4 hours, respectively. A confirmation assay was then sequentially performed, applying a patch with the test item during 4 hours in another two animals. The means of the erythema and edema evaluations at 24, 48 and 72 hours after removing the patch in the animals after a 4 -hour exposure to the test item were 2.11 (erythema) and 0.78 (edema).
Individual skin reactions following 4-hours exposure period
Individual Scores -Rabbit Number and Sex
( 4 )
( 0 )
1 4 Days
( 3 )
Sum of 24 and 72-hour Readings (S) 13
Primary Irritation Index 13/6 - 2.2
( ): total values not used for calculation of the primary index
Cf: crust formation
D: slight desquamation
Le: loss of skin elasticity
Lf: loss of skin flexibility
- : observation not required
Individual daily and mean scores for dermal irritation following 4-hour exposure
Individual Scores - Rabbit Number and Sex
The Acute Dermal Irritation/corrosion assay for the test substance was performed in New Zealand rabbits. 0.5 mL of the test material was applied to a site of about 2.5 x 2.5 cm of intact skin of 3 rabbits and covered by semi-occlusive dressing. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance stepwise at three sites of the skin: site 1 for three minutes, site 2 for 1 hour and site 3 for 4 hours. Any residual test substance was removed by swabbing with cotton wool soaked in 74% Industrial Methylated Spirits. After considerations of the skin reactions produced on the first animal, the remaining two animals were exposed to the test substance for 4 hours. The treated areas of the animals were examined for erythema/eschar and oedema as well as other local skin alterations approximately 1, 24, 48, and 72 hours after patch removal. Additional observations were made on days 7 and 14 to assess the reversibility of skin reactions. Dermal alterations were scored according to OECD guideline nº 404. Well-defined erythema was noted at two treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations. Slight oedema was noted at two treated skin sites one hour after patch removal. Very slight oedema was noted at two treated skin sites at the 72-hour observation.One treated skin site appeared normal throughout the study.Crust formation was noted at two treated skin sites at the 7-day observation with slight desquamation at these two treated skin sites at the 14-day observation. No corrosive effects were noted.
Table 1: Individual scores and total scores for ocular irritation
Rabbit Number and Sex
IPR - 3
10 Male (2.95)
Time After Treatment
Degree of Opacity
Area of Opacity
A - Redness
B - Chemosis
C - Discharge
d: dulling of the normal lustre of the cornea
V: vascularisation, localized in growth of vessels for approximately 1 to 2 mm
The Acute Eye Irritation/Corrosion study for the test substance was performed in New Zealand White rabbits. 0.1 mL of the test material was instilled into the conjunctival sac of the right eye. The eye was held closed for about one second to prevent loss of the test substance. The left eye remained untreated and served as a control. Assesment of ocular damage/irritation was made immediately after the administration of the test material, and approximately after 1 hour, 24, 48 and 72 hours following treatment. Additional observations were made on days 7 and 14 to assess the reversibility of the ocular effects. Based on the results, the test substance was considered to be severe irritant so the test was performed only in one rabbit. One hour after treatment a dulling of the normal lustre of the cornea, iridial inflammation, and conjunctival moderate irritation were noted. Irial inflammation was persisted for 72 hours. Severe conjuctivial irritation and opalescent opacity in the cornea were noted at 72 hours after treatment. Vascularisation, with a localised in growth of vessels for approximately 1 to 2 mm, was noted at the 7-day observation. The treated eye appeared normal at the 14-day observation. The test substance produces ocular irritation in rabbits. The treated eye appeared normal at the 14-day observation.
The Garcia (2006) and Sanders (2000) studies are GLP studies according to OECD guideline 404 and EU guideline B.4.
Garcia tested a 30% pure solution while Sanders tested a 79% pure solution. These two studies had an observation period of 14 days. The other reliable studies did not observe skin effects up to 14 days after exposure. However, the results of these studies as well as of the non reliable studies were consistent.
Based on the available data, the test materials would be classified as irritating according to Directive 67/548/EEC. However, taking into account the criteria established under CLP Regulation, the substance would not be classified.
Since no data is available on the pure substance, taking into account the worst case, the proposal is to classify the substance as a Skin Irritant Category 2.
There are ten studies available performed according to or similar to OECD guideline 405.
The only Klimisch 1 scored study (Garcia, 2006) was performed using a 30% solution of the test substance in water. Only 1 animal was tested, which showed irreversible effects even after 21 days of observation. According to this study the substance should be classified as Eye Dam 1 H318 (CLP) and R41 (DSD).
Sanders (2000) performed a study using a 79% pure substance on 1 animal only. As the observed effects were reversible and not severe enough to allow classification as corrosive to the eyes, the substance was tested in 2 additional animals. No definitive conclusion can be drawn on the classification based on this study.
Several solutions have been tested in the 7 remaining studies. The 3 studies by Sterner et al. did not observe the animals for 21 days, so no conclusions can be drawn on reversibility of effects and therefore no definite classification can be derived. In the three studies solutions of 5%, 10% and 20% were tested, having pH values of 5.5, 8.0 and 4.9, respectively, which seems not logical.
Two studies by Thompson using solutions of 5% and 35% showed irreversible eye effects after 21 days. Based on these studies the substance should be classified as Eye Dam 1 H318 (CLP) and R41 (DSD).
An eye irritation study by Haynes (1983) showed reversible eye effects, although the observation period was only 72 hours. Given the slight effects it can be expected that the effects are fully reversible at 21 days. Therefore, the test substance (probably a 30% solution) should not be classified for eye irritation.
Two studies by the Goldschmidt GmbH (1976) showed full reversibility of the effects within 7 days (5% solution tested) or 14 days (30% solution tested). According to the criteria of CLP, both solutions should be classified as an eye irritant.
Taking all eye irritation data together, the results are sometimes conflicting. Mostly dilutions between 5% and 35% have been tested, which sometimes showed irreversible eye effects. Therefore, it is concluded that the pure substance should be classified as Eye Dam 1 H318 (CLP) and R41 (DSD).
Skin irritation: Based on the available data, the substance is classified as irritating according to Directive 67/548/EEC. However, taking into account the criteria established under CLP Regulation, the substance would not be classified.
Since the tested substance had a purity/concentration of 79% and since no data is available on the pure substance, taking into account the worst case, the proposal is to classify the substance as a Skin Irritant Category 2 H315.
Eye irritation: Based on the above weight-of-evidence approach, the substance is classified as severe eye irritant (R41) according to Directive 67/548/EEC and as Eye Dam. 1 H318 according to CLP.
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