Registration Dossier

Diss Factsheets

Administrative data

Description of key information

For skin irritation, three in vivo studies were available. The method was different from the OECD 404 test guideline. Nevertheless they were all adequate, reliable and relevant, therefore they were considered Weight of Evidence or supporting. In a first study 3 young adult New Zealand White rabbits were dermally exposed to 50% act.ingr.) to two intact and two abraded skin areas of each animal. In a second study, 6 albino rabbits were dermally exposed to an aqueous solution with 4.9% act.ingr. A third study was carried out on 12 human females with Sample A (5% act.ingr.) and Sample B (0% active ingr.). The reversibility of the dermal effects cannot be evaluated and the scoring systems were different from current standards. Although there were signs of irritation on abraded skin, there were no relevant effects on intact skin, therefore classification is not warranted at 50% or lower concentration. A subgroup category 2 classification is proposed at higher concentrations.

For eye irritation, three in vivo studies were available, however the method was different from the OECD 405 test guideline. Nevertheless they were all adequate, reliable and relevant, therefore they were considered Weight of Evidence. In a first study a solution with 50 % act. ingr. was instilled into the conjunctival sac of the right and left eye of 3 New Zealand White rabbits. In a second study a solution wiht 24.5% act.ingr. was instilled into the conjunctival sac of 3 rabbits. In a third study a solution with 4.9% act. ingr. was instilled into the conjunctival sac of six White New Zealand rabbits. in the first study, slight conjuntival redness was seen in 2 animals but everything reversed by 96h. In the second study animals were observed for up to 18 days. Eyes showed at 24 h scoring cornea opacity score 0.25 to 1, which was fully reversible within all animals at the 48 h scoring. Iritis score 1 was seen in all animals at 24 h scoring, which was fully reversible in 72 h. After 24 hours all animals exhibited conjunctival redness score 1.5 or 2 and chemosis score 1 or 2, which w were fully reversible in all animals at the 7 day scoring. Discharge score 1 or 2 was observed after 24 hours in all animals adn fully reversible in all animals. In the two further subgroups the eyes were washed, 2 respectively 4 seconds after test substance instillation, 5/6 animals showed less severe eye reactions. However in subgroup 3 (washed 4 seconds after test substance instillation), one animal showed eye reactions up to 17 days. The eye reactions of this animal were completely reversible at day 18. In the third study a very slight reddening of the conjunctiva (erythema score 1) in 2/6 animals and slight increased mucous secretion (discharge score 1) in 1/6 animals were fully reversible 2 days post dosage. In conclusion there were no relevant effects on eye that triggered classification in the 50, 24.5 and 4.9% concentration. A subgroup category 2 classification is proposed at higher concentrations.

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

For skin irritation, three in vivo studies were available. The method was different from the OECD 404 test guideline. Nevertheless they were all adequate, reliable and relevant, therefore they were considered Weight of Evidence or supporting.

In a first in vivo skin irritation study (Evonik, 1983) 3 young adult New Zealand White rabbits were dermally exposed to 0.5 mL of SBU 185 (50% act.ingr.) to two intact and two abraded skin areas of each animal. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 72 hours. The scoring system was not specified, but most probably the scoring system according to Draize was used. The intact skin showed no erythema, edema or any other tissue reactions at all after 24 and 72 h. The abraded skin showed also no edema reactions after 24 and 72 hours. After 24 hours slight to well-defined erythema reactions were observed in all animals. After 72 h 2/3 animals showed very slight or well defined erythema at one of the two treated sites, each. The erythemas were confined to abrasions.

In a second in vivo skin irritation study (Evonik, 1981) 6 albino rabbits were dermally exposed to 0.5 mL per area of a aqueous solution of REWOCID SBU 185 (10 % as is; 4.9% act.ingr.). The substance was applied for 24 hours to abraded and intact shaved body surface areas under occlusive conditions. The observation time did not extend beyond 72 hours, even though dermal responses were still present at this time. Therefore, the reversibility of the dermal effects cannot be evaluated and the severity of the skin irritation potential of the test substance cannot be classified. Solid content of SBU 185 according to producers information: minimum 49 %. Taking this value into account, solid content of the test solution was 4.9 % in minimum. The study is not considered adequate for classification due to the low % active ingredient.

A third in vivo human skin irritation study (Evonik, 1984) was carried out on 12 females with Sample A (SC-154/52A, containing 10% VARSULF SBU-185; VARSULF SBU-185 containing 50% act.ingr.) and Sample B (SC-154-52B, containing 0% VARSULF SBU-185). Both samples were diluted to 10% v/v with distilled water. Each subject received 3 consecutive exposures to the test materials. Each exposure was for 24 hours under semi-occlusive conditions. Under the conditions of this study, occasional cases of slight skin irritation were observed with 10% v/v aqueous solutions of both samples. This irritation was in form of minimal erythema with slight glazing over the patch site. One subject displayed a response of definite erythema with marked glazing. This reaction was observed 24 hours after removal of the third application patch. For each sample, it appears that the incidence of irritation increases with each application. Both samples, under the conditions of this study, appear to be mildly irritating to the skin.

For eye irritation, three in vivo studies were available, however the method was different from the OECD 405 test guideline. Nevertheless they were all adequate, reliable and relevant, therefore they were considered Weight of Evidence.

In a first in vivo eye irritation study (Evonik,1983) 0.1 mL SBU 185 (50 % act. ingr.) was instilled into the conjunctival sac of the right and left eye of 3 New Zealand White rabbits. The eyes were not washed. Animals were then observed for 96 hours. The scoring system was not specified, but most probably the scoring system according to Draize was used. The only effects seen, was conjunctival redness score 1  in 1/3 animals at the 60 minutes reading and in another animal at the 24 h reading. Both animals were free of any symptoms at the next reading.

In a second in vivo eye irritation study (Evonik, 1965) 0.1 mL of SBU 185 (24.5% act.ingr.) was instilled into the conjunctival sac of 3 rabbits. The eyes were not washed. Further two groups of 3 animals each, were treated in the same way, but their eyes were washed 2, respectively 4 seconds after substance instillation. Animals were then observed for up to 18 days. Irritation was scored by a method comparable to Draize with the addition of discharge scoring. Eyes remained unwashed showed at 24 h scoring cornea opacity score 0.25 to 1, which was fully reversible within all animals at the 48 h scoring. Iritis score 1 was seen in all animals at 24 h scoring, which was fully reversible in 1/3 animals at 72 h scoring and in the other 2/3 animals at 48 h scoring. After 24 hours all animals exhibited conjunctival redness score 1.5 or 2 and chemosis score 1 or 2. Conjunctival redness and chemosis were fully reversible in all animals at the 7 day scoring. Discharge score 1 or 2 was observed after 24 hours in all animals. After 4 days discharge was fully reversible in all animals. In the two further subgroups the eyes were washed, 2 respectively 4 seconds after test substance instillation, 5/6 animals showed less severe eye reactions. However in subgroup 3 (washed 4 seconds after test substance instillation), one animal showed eye reactions up to 17 days. The eye reactions of this animal were completely reversible at day 18.

In a third in vivo eye irritation study (Evonik, 1981), 0.1mL of REWOCID SBU 185 (10 % aqueous solution; 4.9% act. ingr.) was instilled into the conjunctival sac of six White New Zealand rabbits. The eyes were not rinsed after substance application. Animals then were observed for 7 days. Irritation was scored by the method of Draize. REWOCID SBU 185 (10 % aqueous solution) caused up to 24 hours post dosage a very slight reddening of the conjunctiva (erythema score 1) in 2/6 animals and slight increased mucous secretion (discharge score 1) in 1/6 animals. All symptoms were fully reversible 2 days post dosage.

Justification for classification or non-classification

Based on the results of registered substance, and according to the CLP regulation (No. 1272/2008 of 16 December 2008), a subgroup Category 2 classification is proposed with signal word 'WARNING' and hazardstatement H315 'CAUSES SKIN IRRITATION'. However a concentration limit of 50% or less can be applied for the registered substance for non-classification.

Based on the results of registered substance, and according to the CLP regulation (No. 1272/2008 of 16 December 2008), a subgroup Category 2 classification is proposed with signal word 'WARNING' and hazard statement H319 'CAUSES EY IRRITATION'. However a concentration limit of 50% or less can be applied for the registered substance for non-classification.