Butanedioic acid, sulfo-, C-C16-18-alkyl esters, disodium salt

Endpoint summary

Description of key information

Skin irritation:

The registered substance C16 -18 sulfosuccinate was tested in several Human Patch tests for its irritation properties up to a concnetration of 10 % but not in undiluted form.

The test material (C16 -18 sulfosuccinate) was applied to the back of volunteers in concentration of 2, 5 and 10% for 24 hours using the occlusive epicutaneous patch test system. The skin irritation potential of the 2% test dilution was slightly higher and the skin irritation potential of the 5% and 10% test dilution was clearly higher compared to the negative control (Aqua demin.) according to the total irritation score, but clearly lower compared to the positive control. According to the results of this study, the skin tolerability of the test substance in concentration up to 10 % is good to very good (proDerm 2009).

In a second Human Patch test the test material was applied to the back of volunteers in several concentrations up to 10% for 48 hours using the occlusive epicutaneous patch test system. Visual scoring was performed after patch removal (48 and 72 h). Under the conditions of this study, 1% dilution of the test material, did not indicate a clinically significant potential for dermal irritation. Mild to moderate dermal irritation were observed at higher concentrations.

In the third test the test substance (1% dilution) was repeatedly applied on the upper back of the volunteers using an occlusive dressing. Patches were applied 3 times per week for a total of nine applications. Following supervised removal and scoring of the first induction patch, participants were instructed to remove all subsequent Induction patches at home, 24 h after application. The evaluation of this site was made again just prior to reapplication. Approximately 2 weeks after the final induction patch application, a challenge patch was applied to a virgin test site adjacent to the original induction patch site. The patch was removed and the site scored at the clinic 24 and 72h post application. Under the conditions of this study, 1% dilution of the test material, did not indicate a clinically significant potential for dermal irritation or allergic contact sensitization.

The read-across substance C12 -18 sulfosuccinate was predicted to be non-corrosive and non-irritant to human skin based on the three-dimensional human skin model. Viability values were 78.8% and 74.9% in the corrosivity test and 98.3% in the irritation test (all >50% threshold values), therefore it can be considered to be non-irritant to human skin.

The skin irritation properties of the homolog substance C16 -18, C18 unsatd. sulfosuccinate was investigated in in-vivo tests.

The test item was tested for its primary skin irritation under occlusive conditions on the shaved back skin of 4 rabbits. After a contact time of 4 hours, the skin reactions were evaluated. Moderate skin reactions disappeared totally within 10 days. The test substance proved to be moderately irritating on the skin according to the conditions applied.

In another in-vivo test, the undiluted test substance was tested for acute dermal irritation on the dorsal shaved skin of the rabbit in a dose of 0.5 g. The contact time under semi-occlusive conditions lasted 4h. In all animals up to moderate erythema and edema were observed during the first 72 hours after exposure. Two experimental animals showed a brownish discolouration additionally. The skin of all animals showed eschar on day seven and day 14 after exposure. The irritation effects (slight erythema) of two experimental animals persisted longer than 21 days. The observed effects of the other experimental animal reversed completely within 21 days. The test substance proved to be moderately irritating on the skin according to the conditions applied.

Taken together, the tested sulfosuccinates showed slight to moderate skin irritation properties in undiluted form. It is concluded that the target substance C16 -18 sulfosuccinate has not to be labeled as skin irritant.

Eye irritation:

Eye irritation data were not available for the undiluted registered substance.

The test substance C16 -18 sulfosuccinate (5% suspension) was tested in the in-vitro BCOP assay for its eye irritation properties. The test item was applied to corneas and incubated for 10 minutes at 32 °C. After incubation the corneas were washed and incubated for another 120 minutes. Opacity was measured before and after treatment and after postincubation time. After the opacity measurements permeability was determined with a fluorescein solution. With the negative control neither an increase of opacity nor permeability of the corneas could be observed. The positive control showed clear opacity and distinctive permeability of the corneas.

The test item did not cause any opacity or permeability of the corneas. In conclusion, it can be stated that under the conditions of this study, the test item is not considered to be an eye irritant.

However read across data were available from a homolog susbstance, CAS No. 37294 -49 -8 (disodium C-isodecyl sulphonatosuccinate), showing 24 -48h scores of 20.6/80 for cornea, 1.9/10 for iris and 4.1/20 for conjuctiva irritation, with 6/6 eyes positive for corneal opacity and 3/ 6 with iritis. As observations were only performed up to 72 hours, reversibility could not be scored.

Data from another read-across substance (C16 -18, C18 unsatd.) also showed skin irritation potential. The undiluted test substance was tested for acute eye irritation (24 h contact) of three rabbits. The single instillation dose, which amounted to 0.1 ml, is placed in the conjunctival sac of the eye. The observed conjunctival reactions were mild to moderate. Weak corneal opacities were observed additionally. All reactions disappeared completely within 14 days. The test substance proved to be moderately irritating to the eye according to the conditions applied. The GHS criteria for classification and labelling were met.

In summary, worst case classification Eye Damage class 1 is proposed.

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:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

-A first in vitro study was conducted to study corrosive properties by means of a three-dimensional EST-1000 human skin model (Flügge, 2013a). The test item containing >95% active ingredient was applied to the skin surface. In comparison to the negative controls, the mean viability of cells exposed to the test item was 78.8% after a 3-minute exposure period and 74.9% after a 1-hour exposure.The values were well above the cut-off percentage cell viability values distinguishing corrosive from non-corrosive test items of <50% or <15% for a 3-minute or 1-hour treatment, respectively. Therefore, the test item was non-corrosive in this skin model and is predicted to be non-corrosive to human skin.

-A second in vitro study was conducted to determine irritating properties by means of the three-dimensional EST-1000 model of human skin (Flügge, 2013b). The test item containing >95% active ingredient was applied to the skin surface for 20 minutes, followed by refreshment of the medium and a further incubation period of 42 hours. The mean viability of the cells exposed to the test item was 98.3% of the mean negative control value. The value was well above the cut-off percentage cell viability value that distinguishes irritant from non-irritant test items of >50% for a 20-minute exposure. The test item was considered to be non-cytotoxic and predicted to be not irritant to skin.

- According to ECHA progress report 2010 (p 32), it is accepted that in vitro methods for skin irritation represent a full replacement of the in vivo method in a tiered testing strategy and in conjunction with in vitro skin corrosivity tests, if necessary. A negative result in the human skin model for irritation does not need to be confirmed by additional testing.

In conclusion, the test substance was predicted to be non-corrosive and non-irritant to human skin based on the three-dimensional EST 1000 human skin model, therefore no classsifciation is needed.

Eye irritation

Eye irritation data were not available for the registered substance, however read across data were available from a category member, CAS No. 37294 49 -8 (disodium C-isodecyl sulphonatosuccinate). In a key study, 6 Male albino rabbits underwent an eye irritation test with 0.1 mL test item containing +- 50% act. ingr. according to FHSA procedure (Carpenter, 1971). Scoring according to Draize et al. (1944) demonstrated mean 24 -72h scores of 20.6/80 for cornea, 1.9/10 for iris and 4.1/20 for conjuctiva irritation, therefore the substance was concluded to be irritating to the rabbit eye (by FHSA definition), with 6 of 6 eyes positive for corneal opacity and 3 of 6 with iritis.As observations were only performed up to 72 hours, reversibility could not be scored.

In conclusion worst case classification CLP class 1 is proposed.

Conclusion

- Taken together, the registered substance has no to be classified regarding skin irritation.

- Eye irritation data from read-across substance CAS No. 37294 -49 -8 (disodium C-isodecyl sulphonatosuccinate) indicated a worst case classification CLP class 1, which was also accepted as group classification. Further information supporting the classification CLP 1 for eye damamge is provided in the read across justification for the Mono-ester group.

Justification for classification or non-classification

Based on these results and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), the test substance is not classified and has no obligatory labelling requirement for skin irritation.

Based on read across with structural analogues, the test substance needs to be classified to the Directive 67/548/EEC, Annex VI with symbol Xi and risk phrase R41- Risk of serious damage to eyes. According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance is classified as Category 1, with signal word 'Danger' and hazard statement: H318 -Causes serious eye damage.