Enbucrilate

Endpoint summary

Description of key information

SKIN IRRITATION:
- REACH_slightly irritating | rabbit | OECD 404 | LID-1187A #key study#

EYE IRRITATION:
- REACH_Lit_well tolerated | rabbit | Toxicity study of Butyl 2-Cyanoacrylate (Alejo et al) |
- REACH_Lit_improvement of healing process | rabbit | Use of n-butyl cyanoacrylate for corneal rhaphy (Mota et al) |
- REACH_Lit_acceptable inflammatory reaction | rabbit | Tissue Adhesives for a Sutureles Fadenoperation (Tonelli et al) |

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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Various studies are available to assess the acute dermal irritation/corrosion of n-butyl cyanoacrylate in rabbits. The substance was directly tested on non-abraded and abraded skin. Cured patches were also tested on non-abraded and abraded skin. Moreover, extracts of cured material were evaluated for their potential to produce irritation after intracutaneous injection according to ISO 10993-10 (1996), Biological Evaluation of Medical Devices Part 10: Irritation and Sensitization Test.

As the OECD guideline 404 requires testing of substances on intact skin, those studies are ranked highest in quality. The test with fresh, uncured material reflects the realistic exposure situation on skin best and is thus judged to be the key study.

Under the conditions of this test, direct application of n-butyl cyanoacrylate was considered to be 'slightly irritant' to intact skin. The classification criteria under CLP are not fulfilled.

Eye irritation

The safety of n-butyl cyanoacrylate has not been tested on corneal tissue specifically with regard to eye irritation as described under the international OECD standard guideline. However, some medical investigations on rabbit eyes have been conducted in order to proof the suitability of this substance as tissue glue for repairing injuries on the eye (Alejo, 1973, Mota, 2004, Tonelli, 2004). The studies concluded that n-butyl cyanoacrylate is well tolerated basically in contact with cornea. No irritation is described. Some cytotoxic reactions have been observed as well as inflammatory responses; however, it needs to be considered that the rabbit eyes have been severely injured before application of the glue. Use of the glue for proof of compatibility would have been unfeasible in case of irritating properties of n-butyl cyanoacrylate. It is thus concluded, based on the weight-of-evidence from the rabbit experiments, that this substance is not irritating to rabbit’s eyes.

 

Moreover, much experience from clinical observations and investigations in humans is available (see also summary of supportive data in chapter 7.10).

Various authors describe that the use of n-butyl cyanoacrylate (as well as the structural analogue isobutyl cyanoacrylate) offers a safe technique for healing corneal wounds and is an effective alternative to classical sutures (e.g. in scleral tunnel cataract surgery or for treatment of corneal perforations). The case reports and clinical studies describe a direct application of the adhesive onto the eye (cornea) which gives an indication on the compatibility of the tissue adhesive on eyes. It is summarized that n-butyl cyanoacrylate can well be used as wound barrier in ocular surgery with a low side effect profile. Irritation was not mentioned in any of the publications as contraindication for the use of n-butyl cyanoacrylate in eye surgery.

 

The overall weight-of-evidence taken from a literature search on the use of n-butyl cyanoacrylate as tissue adhesive in ocular surgery in rabbits and humans indicates that this substance is very likely not irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:
see discussion section

Justification for selection of eye irritation endpoint:
see discussion section

Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Skin irritation

Based on the overall weight-of-evidence resulting from investigations on n-butyl cyanoacrylate in OECD and ISO standard tests, it is concluded that n-butyl cyanoacrylate is not classified as irritating to the skin.

Eye irritation

The overall weight-of-evidence taken from a literature search on the use of n-butyl cyanoacrylate as tissue adhesive in ocular surgery in rabbits and humans indicates that this substance is very likely not irritating to eyes.