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Description of key information

Alkyl 2-cyanoacrylates such as ethyl 2-cyanoacrylate (ECA) are known to polymerize rapidly in the presence of water. According to Annex XI of the REACH Regulation, a test can be waived for technical reasons if the test substance is e.g. highly active. Study data shows that the polymerisation of ECA takes at maximum a few minutes to be completed, depending on the specific conditions of reaction (see 7.1.1. Basic toxikokinetics, study on polymerisation speed). This is supported by the statement by Krall et al. (1983) that alkyl 2-cyanoacrylates "polymerize on and adhere to moist living tissues". This effect is the basis for using this substance class as tissue adhesives in medical applications.

Both, the study by Ousterhout et al. included in IUCLID section 7.1.1. and the acute oral study included in section 7.2.1 show, that oral application of fast reacting cyanoacrylates, including ECA, results in the immediate generation of a polymeric material on the mucosa or in the cavities of the gastro-intestinal tract. Effects exerted by this material and its potential degradation products do not represent the intrinsic properties of the monomeric ethyl 2-cyanoacrylate, for which systemic availability at relevant doses can be excluded.

Similar effects would be expected by exposure via the inhalation route, where ECA quickly polymerizes in the humidity of the respiratory tract. For the same reason, a dermal repeated dose study is technically not feasible. Via all routes, exposure will finally occur to the polymer and not to monomeric ECA. The intrinsic property to polymerize in the presence of water limits the absorption of cyanoacrylates via all three routes (oral, dermal, inhalation).

Since the intrinsic hazard of ECA cannot be evaluated in repeated dose studies, the studies are waived according to REACH Annex XI, section 2. This is in accordance with the ECHA guidance (chapter R.5, version 2.1 of December 2011), in which in chapter R.5.2.2 the example of a substance having a high reactivity with water is explicitly mentioned as a case where testing might not be feasible for technical reasons.

References:

Krall R. E., Neuwirth R. S. and Richart R. M., Pharmacology and Toxicology of Methyl Cyanoacrylate, Fem. Transcervic Steril., Proc. Int. Workshop, 1983, pp175 -185

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: oral
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: inhalation
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
chronic toxicity: dermal
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification