Registration Dossier

Administrative data

Description of key information

Both  a primary dermal irritation study in rabbits (20% formulation) and human patch test with registered substance (purity not specified) indicated that there was no irritation potential. Read across substance CAS 37294-49-8 (Butanedioic acid, sulfo-, 1,4-diisodecyl ester, sodium salt ) containing 50% active ingredient was demonstrated not to be a skin irritant based on primary irritation score of 0.375/4 and reversible findings within 72h. Further weight of evidence was provided by read across substance CAS 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts) containing >95% active ingredient which was also predicted to be non-corrosive and non-irritant to skin  based on the three-dimensional EST 1000 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. Nevertheless a subgroup classification CLP category 2 was proposed for skin irritation, with application of concentration limit of 20% for the registered substance for non-classification.
For eye irritation, supporting studies for the registered substance, including a rabbit study (5% formulation) and an in vitro study (unspecified concentration) already indicated irritation. However from a key study with read across substance CAS 37294-49-8 (Butanedioic acid, sulfo-, 1,4-diisodecyl ester, sodium salt) containing 50% active ingredient, mean 24 -48h scores were 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, and worst case classification CLP class 1 was proposed, with application for the registered substance of concentration limits of 20% or less for CLP category 2 classification, and 5% or less for non-classification.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation was assessed based on supporting data from registered substance and weight-of-evidence information from read-across:

A separate read across justification document for the mono-ester sulfosuccinates is provided in Section 13.

- In a supporting primary dermal irritation study with the registered substance, six New Zealand White rabbits were dermally exposed to 0.5 mL of test item (20% act.ingr. in water) (Consultox Laboratories Ltd, 1969a). Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 72 hours. Irritation was scored by the method of Draize test. There was no irritation at all throughout the test.

- In a supporting human test with registered substance, 20 test persons (19 females and 1 male) between 33 and 56 years of age (that had not used cosmetics during 3 days before the test), were exposed on the forearms for 24 hours to the test item under gauze occlusion, followed by methylene blue exposure to measure tensio-active effect (Biefeldt and Schrader, 1991). The test formulation showed a strong roughening effect. The test item in this test turned out to do only slightly better than sodium lauryl sulphate. The test method is not a regulatory standard method for skin irritation.

- Weight of evidence from read across data were available from category member, CAS No. 37294-49-8 (Disodium C-isodecyl sulphonatosuccinate), for which an in vivo study was done in male albino rabbits under covered application to the clipped intact and abraded skin of 0.5 mL test item containing +- 50% act. ingr. (Carpenter, 1971b). Scoring according to Draize et al. (1944) demonstrated a primary irritation score of 0.375, based on erythema which was reversible within 72 hours. It was concluded that the test item was not irritating to the rabbit skin.

- Additional weight of evidence was generated from read across substance CAS No. 90268-36-3 ( Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts):

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 was predicted to be non-corrosive to human skin.

A second in vitro study was conducted with the same read across substance CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-alkyl esters, disodium salts) 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. Taking into account all the above information, the registered test substance is considered not to be irritating for skin.

In conclusion, the test substance was predicted to be non-corrosive and non-irritant to human skin and found non-irritating in in vivo testing.

Nevertheless a subgroup classification CLP category 2 was proposed for skin irritation, with application of concentration limit of 20% for the registered substance for non-classification.

Eye irritation was assessed based on supporting data from registered substance and weigth-of-evidence information from read-across:

A separate read across justification document for the mono-ester sulfosuccinates is provided in Section 13.

- In a supporting primary eye irritation study the registered test substance (5 % act.ingr. in water) was instilled into the conjunctival sac of the left eye of 9 New Zealand White rabbits (Consultox Laboratories Ltd, 1969b). The eyes of three animals, respectively were washed 2 sec and 4 sec after substance instillation. The eye of three animals remained unwashed. Animals were then observed for 7 days. Irritation was scored by the method of Draize. Irritation was confined to the conjunctiva. Cornea or iris was not involved. Conjunctival effects of the test item were fully reversible at day 3 in the unwashed eye. In this study, the test item is mildly irritating to the eye based on ocular reactions at 24, 48, and 72 hours p.a., using the Draize test (Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics FDA, 1959).

The findings however did not result in the need of classification.

- In a supporting in vitro test on bovine red blood cells, haemoloysis and denaturation were measured after exposure to the test item, followed by calculation of a mean ocular irritation index (Löffert and Lang, 1992). The test formulation showed an L/D value of 0.8, representing for an irritating effect. The test method however is not a regulatory standard method for eye irritation.

- Read across data were available from category member, CAS No. 37294-49-8 (Disodium C-isodecyl sulphonatosuccinate), for which a key in vivo study was done in 6 male albino rabbits given 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 -48h score 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 and worst case classification CLP class 1 was proposed.

- In conclusion, the registered substance can be considered to evoke severe damage to the eye, therefore CLP class 1 is proposed. However a non-classification threshold to CLP class 2 (eye irritating) can be applied for a formulation containing 20% active ingredient or less, whereas non-classification can be applied for formulations of 5% or less.

 

Conclusion

- Based on the available data of registered and read across substances, a subgroup classification CLP category 2 is proposed, however with concentration limit of 20% or less where the registered substance can also be accepted to be non irritating for skin.

- Based on the available data of registered and read across substances, the substance needs to be classified as causing severe damage to the eye. A classification threshold to CLP class 2 (eye irritating) can be applied for a formulation containing 20% active ingredient or less, whereas for formulations of 5% or less no classification is needed.

- Further information is provided in the read across justification for the Mono-ester sulfosuccinate subgroup. 


Justification for selection of skin irritation / corrosion endpoint:
The in vivo study with highest concentration test material was selected.

Justification for selection of eye irritation endpoint:
key study

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on these results of registered and read across substances, and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), a subgroup classification “Xi” and the risk-phrase R 38 or Category 2 classification is proposed with signal word 'WARNING' and hazard statement H315 'CAUSES SKIN IRRITATION'. However a concentration limit of 20% or less can be applied for the registered substance for non-classification. There is a subgroup classification for category 2 CLP for skin irritation, however, a concentration limit of 20% or less can be applied for non-classification.

Based on results of registered and read across substances, 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. A specific concentration limit can be applied for formulations containing 5 to 20 % active ingredient, with phrase R36 - Irritating to eyes or CLP Category 2, signal word 'Warning' and hazard statement H319 - Causes serious eye irritation. At and below 5 % there is no classification needed.