Registration Dossier

Administrative data

Description of key information

The available data suggest that amides, C8-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl) is moderately and highly irritating to the skin and eyes, respectively.

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

A OECD guideline study was conducted to assess the skin irritation potential of amides, C12-18 (even numbered) and C18-unsatd., N, N-bis(hydroxyethyl) in rabbits. The shaved skin of 5 rabbits was exposed to the undiluted test substance using occlusive patches for 4 hours. The skin was then observed for effects (scored according to the Draize system) for 21 days after patch removal. Exposure to undiluted test substance caused light to moderate erythema and light oedema immediately after removal of the patch. The reactions intensified until the 72 hour observation time point when strong erythema and moderate to strong oedema, as well as eschar formation were seen. No or only traces of the eschar were left in 1/5 and 4/5 animals, respectively, after 21 days. The acute reactions were no longer visible after 14 days. Based on these results, a mides, C12-18 (even numbered) and C18-unsatd., N, N-bis(hydroxyethyl) was considered irritating to skin (Kästner, 1986).

An OECD guideline study assessed the irritation potential of structurally similar amides, C8-18 and C18-unsatd., N, N-bis(hydroxyethyl) in rabbits. The test substance was applied undiluted to rabbit skin under an occlusive bandage for 4 hours, then washed with warm water. Animals were then observed for 25 days. Strong erythema and strong oedema were observed in all animals. Slow recovery occurred, under thick scabs. After 25 days, 2/3 animals had fully recovered. In the third animal, scabs were falling away. The overall irritation index was 7 out of 8 which can be considered as highly irritating to rabbit skin (Mürmann P, 1990a).

Eye irritation

A study was performed to assess the eye irritation potential of amides, C12-18 (even numbered) and C18-unsatd., N, N-bis(hydroxyethyl). Four rabbits received 0.01 mL of an undiluted solution of the test substance in one eye. The other eye remained untreated. After 1, 6, 24, 48 and 72 hours, then 7, 10, 14, 17 and 21 days, eyes were analysed for reactions based on the Draize appraisal method. On the cornea, slight to moderate opacity was observed in all treated eyes. The reaction was irreversible. Irreversible effects were also noted in the iris of one animal. Finally, all animals presented moderate to severe redness, chemosis, and/or exudation (sometimes infiltrated with blood) of the conjunctivae, which did not entirely disappear by the end of the 21 day observation period. Amides, C12-18 (even numbered) and C18-unsatd., N, N-bis(hydroxyethyl) was considered highly irritating to eyes (Kästner, 1987).

In another OECD guideline 405 study, the eye irritation potential of structurally similar amides, C8-18 and C18-unsatd., N, N-bis(hydroxyethyl) was assessed in rabbits. The test substance was applied neat to the left eye of three rabbits. Two out of three animals showed opacity of the cornea as well as slight corneal reddening and circumcorneal injection. These effects were reversible within 10 days. In all animals, moderate to strong erythema and slight swelling of the conjunctivae were noted. This was reversible within 13 days. The overall irritation index was 34.9/110. The results obtained in this study suggest that amides, C8-18 and C18-unsatd., N, N-bis(hydroxyethyl) is a moderate eye irritant (Mürmann P, 1990b).


Justification for selection of skin irritation / corrosion endpoint:
Sufficient data available to evaluate this endpoint.

Justification for selection of eye irritation endpoint:
Sufficient data available to evaluate this endpoint.

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin

The key study, which is reliable without restrictions (GLP compliant, included use of the appropriate number of animals), clearly demonstrated that a 4 hour, occlusive exposure to amides, C12-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl) was irritating to the skin of rabbits. In a supporting study, structurally similar amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl) was highly irritating to the skin of rabbits. However, the supporting study was performed without GLP and the number of animals tested was lower than that recommended in the OECD guideline 404. The data support an R38 classification and Skin Irritation Category 2; H315-causes skin irritation (hazard statement), according to EC (67/548/EEC) and CLP criteria (EC 1272/2008), respectively.

Eye

The available in vivo eye irritation studies suggest amides, C12-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl) is highly irritating to eyes. The key study reported irreversible eye effects in one animal, while in the supporting study, conducted on structurally similar amides, C8-18 and C18-unsatd., N,N-bis(hydroxyethyl), reversible positive responses (corneal opacity, conjunctival redness and oedema) were seen in 2/3 animals. The results of the key study meet the criteria for classification of amides, C12-18 (even numbered) and C18-unsatd., N,N-bis(hydroxyethyl)as Xi; R41, and irreversible effects on the eye, Category 1; H318 – causes serious eye damage (hazard statement), according to EC (67/548/EEC) and CLP (EC 1272/2008).