Registration Dossier

Administrative data

Description of key information

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

A study equivalent to OECD 439 (In Vitro Skin Irritation) was performed to assess the skin irritation properties of 2-phenylethyl cyanoacrylate. 2-Phenylethyl cyanoacrylate showed virtually no effects on the skin models, resulting in a mean viability of the tissues of about 97 % compared to the negative control. According to this result, 2 -phenylethyl cyanoacrylate is considered to be non-irritant.

The study result is in line with several clinical investigations that demonstrate the well-established use of long chain alkyl 2 -cyanoacrylates, e.g. 2-octyl cyanoacrylate as an effective alternative to conventional sutures in closing surgical incisions in humans. Such 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 these publications.

Eye irritation

The eye irritation properties of 2 -phenylethyl cyanoacrylate were assessed by an HET-CAM study using the endpoint assessment method. According to the irritation score which was found to be 0, 2 -phenylethyl cyanoacrylate did not induce any irritative effects.

It was observed during the study that the substance builds a polymeric sticky sheet on the CAM that can be removed without significantly damaging the CAM by using forceps. This observation indicates that testing of 2-phenylethyl cyanoacrylate in vivo might result in irritative effects based on the fact that solid polymeric particles will constantly scratch the eye's surface. It is therefore concluded that an in vivo study is not justified in this case.

The result on eye irritation for 2 -phenylethyl cyanoacrylate are in line with a variety of clinical investigations that demonstrate the successful use of the homologeous 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 not 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.

Justification for classification or non-classification

Skin irritation

Based on the in vitro skin irritation study performed with 2 -phenylethyl cyanoacrylate, and considering the overall weight-of-evidence resulting from other cyanoacrylate homologues, it is concluded that 2-phenylethyl cyanoacrylate is not classified as irritating to the skin.

Eye irritation

Based on the HET-CAM study performed with 2 -phenylethyl cyanoacrylate, and considering the overall weight-of-evidence

resulting from other cyanoacrylate homologues, it is also concluded that 2-phenylethyl cyanoacrylate is not classified as irritating to the eyes.