Mecrilate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In general, cyanoacrylates react rapidly in contact with water to form polymers (within seconds) in exogenous reactions. It is thus technically not easy to assess the skin sensitizing potential of the isolated methyl 2-cyanoacrylate (MCA) monomer. It can be expected that during the test procedure the monomer reacts with the humidity of the air and on the skin to form the polymer. This reaction is expected to be much faster than a penetration through skin, making it practically impossible to expose cells involved in an allergic reaction to the monomeric substance.

 

In the key study (Parker & Turk, 1983), the potential of methyl 2-cyanoacrylate (MCA) to induce skin sensitization was assessed with the Polak method in Guinea pigs. In contrast to other acrylic compounds, MCA did not induce skin sensitization. The authors concluded on the basis of 21 tested acrylate and methacrylate compounds, that those structures with substitution on carbon 2 (such as MCA), were not able to induce skin sensitization. In the same publication, it is described that the structural homologue butyl 2-cyanoacrylate (BUCA) did not induce skin sensitization, either. BUCA differs from MCA by a longer side chain that contains four carbon units instead of one.

Further two studies with BUCA were conducted using a modified Buehler protocol. In both tests, the liquid formulation was applied to the animals’ flanks directly for induction. For the challenge phase, the adhesive was allowed to cure at room temperature for 20 min in experiment 1 (R0900107) and for 30 min in experiment 2 (R0900106). In experiment 2, another commercial formulation was investigated as additional control. Experiment 1 resulted in a positive reaction indicating a skin sensitizing potential of the formulation. Experiment 2, however, did not display any skin reactions making the authors conclude that under the conditions of this study, repeated dermal application of both commercial formulations did not cause delayed contact hypersensitivity in guinea-pigs. However, it was considered that one formulation has the potential to cause delayed contact hypersensitivity from the first experiment, but the degree of patch curing was critical.  

To account for the potential influence of possible monomeric residues as well as additives, or degradation products from the n-butyl cyanoacrylate polymer, extracts of the cured polymer have been prepared in cotton seed oil and physiological saline according to standard procedures for medicinal products. The extracts were investigated in the Magnussen-Kligman Maximization test (R0900117). No potential for skin sensitization was observed in two tests compared with negative controls. By using extracts, the leakage of residual monomers and by-products has been covered. The results of two studies with extracts of the cured polymer indicate that n-butyl cyanoacrylate is not sensitizing to the skin.

Allergic reactions towards cyanoacrylate adhesives are described in literature. As the composition of the commercial products has not been described in most of the case reports, it could not be clarified which chemical substances were present and contributed to the adverse skin effects.

 

Considering the widespread industrial and domestic use of cyanoacrylates, sensitization seems to be rare, indicating that cyanoacrylates are not strong skin sensitizers. MCA was discovered in the1950s and introduced as adhesive in the market in 1958 (http://www.nt.ntnu.no/users/skoge/prost/proceedings/aiche-2005/topical/pdffiles/TH/papers/277a.pdf).

Tissue adhesives containing cyanoacrylate are in use for approx. 20 years and are sold in various international markets. One example is Indermil®, which was granted the CE mark in accordance with the European Medical Device Directive (93/42/EEC) in 1995. The US FDA has approved this medical device in 2002. It has not been withdrawn from marketing for any reason related to the safety or effectiveness of the medical device, including skin sensitization. (http://www.accessdata.fda.gov/cdrh_docs/pdf/P010002b.pdf). In consideration of the low number of sensitized persons compared to the widespread use of cyanoacrylates, the German MAK commission revised the evaluation of MCA in 1996. As result, the label ‘S’ for sensitizer is no longer applied (http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb13705d0023/full).

 

It is concluded, based on the overall weight of evidence, that MCA is not sensitizing to the skin.

Migrated from Short description of key information:
On the basis of an in vivo experiment with methyl 2-cyanoacrylate (MCA), four Guinea pig studies with the structural homologue butyl 2-cyanoacrylate and in light of the long history of safe use of cyanoacrylates as tissue adhesives, it is concluded that MCA is not sensitizing to the skin.

Justification for selection of skin sensitisation endpoint:
See discussion.

Justification for classification or non-classification

See discussion.