Enbucrilate

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 n-butyl-cyanoacrylate 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.

 

However, two tests in guinea pigs according to a modified Buehler protocol have been conducted in order to assess the skin sensitizing potential of the substance n-butyl cyanoacrylate supplied in a commercial formulation. 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 additionally investigated as further control.

 

Experiment 1 resulted in a positive reaction indicating skin sensitising 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 made in cotton seed oil and physiological saline according to standard procedures for medicinal products. The extracts were investigated in the Magnussen-Kligman Maximization test. 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.

 

In a publication by Parker and Turk (1983) it was, moreover, demonstrated that butyl cyanoacrylate did not induce contact sensitivity in guinea pigs when tested with the Polak method.

 

Allergic reactions towards cyanoacrylate adhesives are occasionally described in literature. Case reports often lack a clear description which substance caused the observed reactions. Some authors argue that the monomer might be of relevance, others argue that degradation products could have caused reactions. As the full composition of the commercial products have 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.

 

Tissue adhesives containing n-butyl 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). No reports on skin sensitization in relation to exposure to n-butyl cyanoacrylate were found in a literature search.

 

Given the long history of safe use of n-butyl cyanoacrylate in surgery, it is concluded, based on the overall weight of evidence, that n-butyl cyanoacrylate is not sensitizing to the skin.

Migrated from Short description of key information:
- REACH_not sensitising | guinea pig (male/female) | Guinea pig maximisation test | Polymerised Indermil
- REACH_not sensitising | guinea pig (male/female) | Guinea pig maximisation test | Indermil
- REACH_not sensitising | guinea pig (male/female) | OECD 406 | LID-1187A
- REACH_sensitising | guinea pig (male/female) | OECD 406 | LID-1187A
- REACH_Lit_not sensitising | guinea pig (male/female) | Contact sensitivity to acrylate compounds in guinea pigs (Parker, Turk) | 

Justification for selection of skin sensitisation endpoint:
see discussion section

Justification for classification or non-classification

Skin sensitisation

Based on the overall weight of evidence, it was concluded that n-butyl cyanoacrylate is not considered to be a skin sensitizer and thus needs no classification and labelling.