2-Propenoic acid, 2-cyano-, 1-methylheptyl ester

Endpoint summary

Description of key information

skin irritation:
- REACH_not irritating | rabbit | ISO 10993-10 Guidelines | [TN]1-methylheptyl cyanoacrylate[/TN][SPEC][/SPEC][AM]94.5%[/AM]
- REACH_not irritating | rabbit | ISO 10993-6 Guidelines |[TN]1-methylheptyl cyanoacrylate[/TN][SPEC][/SPEC][AM]94.5%[/AM]
- REACH_not irritating | human | [TN]2-Octyl cyanoacrylate[/TN][SPEC][/SPEC][AM][/AM]

eye irritation:
- REACH_not irritating | human | [TN]2-Octyl cyanoacrylate[/TN][SPEC][/SPEC][AM][/AM]

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)

Additional information

Skin irritation

No experimental data from standard OECD tests are available for assessing the skin irritation of 1-methylheptyl cyanoacrylate. However, tests with a formulation containing 94.5% of the substance have been conducted according to ISO standards (intracutaneous injection, subcutaneous implantation). Taking those tests and information from various publications describing the use of the structural analogue 2-octyl cyanoacrylate in surgery into account, an expert judgement on skin irritation is drawn based on the weight-of-evidence and read-across considerations.

 

1-Methylheptyl cyanoacrylate polymerizes in contact with moisture within a few seconds. For assessing the skin irritating properties with respect to the use of a medical adhesive, extracts of pieces of polymerized adhesive have been prepared in 0.9% NaCl and cottonseed oil. No skin irritation was observed in rabbits after intracutaneous injection of 0.2 ml of the extracts. Moreover, implantation of test articles strips (polymerized adhesive) were subcutaneously implanted in rabbit skin. The test articles did not show any remarkable effects regarding inflammation, encapsulation, haemorhage, necrosis, discoloration. In both studies there were no remarkable differences to the controls. It is concluded from those investigations that 1-methylheptyl cyanoacrylate is not irritating to the skin.

 

Additional evidence was collected from literature on the use of cyanoacrylates in skin surgery. A variety of clinical investigations demonstrate the well-established use of 2-octyl cyanoacrylate (and partly N-butyl cyanoacrylate) as effective alternative to conventional sutures in closing surgical incisions in humans. Tissue adhesives are used in different procedures including general surgery, emergency medicine and plastic surgery. The adhesive polymerizes in contact with tissue surfaces in an exothermic reaction in 30-60 sec. From the overall clinical experience, it was concluded that the use of 2-octyl cyanoacrylate is successful, safe and well accepted by patients. No adverse health implications with regard to skin irritation have been described in any of the mentioned publications.

 

Based on the overall weight-of-evidence resulting from investigations on 1-methylheptyl cyanoacrylate in ISO standard tests and from published literature on safe use of the close structural analogue 2-octyl cyanoacrylate in skin surgery, it is concluded that 1-methylheptyl cyanoacrylate is not irritating to the skin.

Eye irritation

The safety of 1-methylheptyl- as well as of 2-octyl cyanoacrylate has not been tested on corneal tissue specifically. However, a variety of clinical investigations demonstrate the successful use of 2-octyl cyanoacrylate as effective tissue adhesive in medical treatments such as blepharoplasty, facial skin closure, cleft lip repair, laparoscopic surgery wound closure, and the treatment of gastric fundal varices (see Meskin et al 2005). The application of cyanoacrylate adhesives has become standard therapy for small corneal perforations due to their ease of use and application and ability to delay surgical therapy. In those cases, the adhesive is directly applied into the eye.

Although the publications do not cover large clinical trials, the case studies presented do give an indication on the behaviour of the tissue adhesive on eyes.

The studies conclude that 2-octyl cyanoacrylate can well be used as wound barrier in ocular (and skin) surgery with a low side effect profile. Reversible eye irritation was reported occasionally. Some patients complained of mild transient foreign body sensation on postoperative day 1. Others had trace diffuse bulbar conjunctival hyperemia or trace focal conjunctival hyperemia adjacent to the wound. However, conjunctival injection, mild corneal edema, or anterior chamber cellular reaction were no more significant than those seen in other routine surgery cases. Irritation was not mentioned in any of the publications as contraindication for the use of 2-octyl cyanoacrylate in eye surgery.

The overall weight-of-evidence taken from a literature search on the use of 2-octyl cyanoacrylate as tissue adhesive in ocular surgery indicates that this substance is very likely not irritating to eyes. Based on the close structural similarity and same reaction mechanism, 1-methylheptyl cyanoacrylate is also considered to be non-irritating to the eyes.

Justification for classification or non-classification

Skin irritation

Based on the overall weight-of-evidence resulting from investigations on 1-methylheptyl cyanoacrylate in ISO standard tests and from published literature on safe use of the close structural analogue 2-octyl cyanoacrylate in skin surgery, it is concluded that 1-methylheptyl 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 2-octyl cyanoacrylate as tissue adhesive in ocular surgery indicates that this substance is very likely not irritating to eyes. Based on the close structural similarity and same reaction mechanism, 1-methylheptyl cyanoacrylate is also considered to be non-irritating to the eyes.