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Administrative data

Description of key information

For skin irritation, there was no study with registered substance but read across data were available from category members (CAS Nos. 2373-38-8 and 577-11-7) demonstrating skin irritation potential. Therefore the registered substance was also considered irritating to skin, as also classified as the other category members. 
For eye irritation, there was a key study with registered substance demontrating irritation. Further read across data were available from category members (CAS Nos. 2373-38-8 and 577-11-7) demonstrating severe eye irritation or damage potential. Therefore the registered substance was also considered to worst case causing severe eye damage, as also classified as the other category members.

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

For skin irritation, there was no study with registered substance but following read across data were available:

- A key study for skin irritation was performed in rats according to OECD 404 test guideline with Docusate sodium (CAS No. 577 -11 -7) (Mürmann, 1988a). A volume of 0.5 mL Docusate sodium (70% solution in ethanol/methanol and water) was applied on 6 cm2 shaved skin of 3 male rabbits by occlusive application. After this period, the skin area was washed with warm water and observed after 1, 24, 48, 72 hours and 6, 8, 10 and 14 days. The results showed that there was an irritation index of 7.8/8 over the 1 -72 hour period and some effects were still visible at 14 days.

- A supporting study was conducted by application of 0.5 mL Docusate sodium to intact and abraded skin of 6 male rabbits according to FHSA (Federal Hazard Act Substance) and CFR 1500.41 method for 24 hours under occlusive dressing (McGinty 1977). The reactions were evaluated after 24 and 72 hours and the substance was strongly irritating as indicated by a mean primary irritation score of 3.83/4.

- A supporting in vivo skin irritation study (Shaffer, 1957) was available where 80% Butanedioic acid, sulfo-, 1,4-bis(1,3-dimethylbutyl) ester, sodium salt (CAS No. 2373 -38 -8) were applied to the closely-clipped skin of male rabbits for 24 hours under occlusion. Doses given were 2.5, 5 and 10 mL test item/kg body weight, corresponding with ca. 9, 18 and 36 g active ingredient. At the dose of 10 mL/kg there was very severe erythema, edema and necrosis of the skin. At 5 and 2.5 mL/kg bw, erythema and edema were initially quite severe, but the edema subsided within 24 to 48 hours. Erythema, however, persisted for 4 to 5 days. The 2 latter doses were considered as worst case situation volumes (9 and 18 g instead of 0.5 g). There were no scores available.

In conclusion, the test item is also considered to be irritating but not corrosive to skin. Further information supporting the classification is provided in the read across justification for the Diester category, showing that all substances in the group (except one) were irritating for skin (justification with data matrix separately attached in Section 13).

Eye irritation

For eye irritation, following study was available for registered substance:

- In a key in vivo eye irritation study (Shaffer et al., 1957b) a quantity of approximately 10 mg of registered substance containing > 97% active ingredient was placed in the conjunctival sac of the left eye of each of 5 male albino rabbits. The lids were held close for about 30 seconds after introduction of the dose, and the eye was examined immediately thereafter, and again over the next several days. There was an immediate reaction of pain or discomfort to application of the dose, but no more serious sign of immediate injury than a somewhat excessive amount of lacrimation. By 24 hours after the dose a moderate degree of conjunctivitis had developed. This subsided gradually over the succeeding 24 to 48 hours and was associated with a certain amount of discharge from the eye. By the fourth day following that of the dose, most eyes had regained their normal appearance, and continued in good condition for the remainder of a seven-day observation period.

In addition, following read across data were available:

- 0.05 mL of Butanedioic acid, sulfo-, 1,4-bis(1,3-dimethylbutyl) ester, sodium salt (CAS No. 2373 -38 -8) containing 80% active ingredient was instilled into the conjunctival sac of the left eye of each of 5 male albino rabbits according to OECD 405 (Shaffer, 1957). There was an immediate reaction of pain, but by four hours after the dose no more serious signs of irritation than profuse discharge was observed. At observation on the following day, the discharge had lessened somewhat, but a moderate degree of conjunctivitis had developed, together with extreme swelling of the lids in two instances. The intensity of these reactions was variable within the group, so that in the case of the two animals noted the severity of irritation was considerably more pronounced than with the others and, in addition, they displayed signs of corneal involvement characterized by diffuse clouding of the entire area. These differences in response are probably attributable to differences in amount of the dose washed out by the initial discharge. However, by the fourth day the pattern of injury was well-developed in all eyes and consisted of moderate discharge, partial closing of the lids by swelling, moderate conjunctivitis, sluggish reaction of the iris to light, and diffuse corneal opacity. This condition persisted with no appreciable improvement for the remainder of a 7-day observation period. There were no scores available.

- 0.1 mL of a mixture of 70% Docusate sodium (CAS No. 577 -11 -7), ethanol in methanol, water was applied to the eyes of 3 male rabbits (Mürmann, 1988b). After 72 hours, fluorescein solution was applied for cornea evaluation and rinsing was performed with warm physiological solution. Evaluation after 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days after application showed irreversible damage (including turbidity of the cornea). The mean overall irritation score for 1 -72 hours was 46,67/110.

- 0.1 mL of Docusate sodium (CAS No. 577 -11 -7) was applied to the eyes of 6 rabbits according to FHSA (Federal Hazard Substance Act) and CFR 1500.41 method. Evaluation after 24, 48 and 72 hours showed that the substance was irritating as indicated by changes of the cornea, iris and conjunctiva up to 72 hour (McGinty 1977).

In conclusion,the test item is also considered to be cause serious eye damage. Further information supporting the classification is provided in the read across justification for the Diester category, showing that all substances in the group were considered to cause serious eye damage (justification with data matrix separately attached in Section 13).


Justification for selection of skin irritation / corrosion endpoint:
Key study

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 the results the test substance needs to be classified for skin irritation according to the Directive 67/548/EEC, Annex VI with symbol Xi and the indication of danger “irritant”; the following risk phrase shall be assigned: R38 - Irritating to skin.  For the eye, it is classified as "Risk of serious damage to eyes" and risk phrase R41- Risk of serious damage to eyes shall be assigned.

According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance is classified as Category 2, with signal word 'Warning' and hazard statement: H315 - Causes skin irritation. For the eye, Category 1, with signal word 'Danger' and hazard statement: H319 -Causes serious eye damage is assigned.