Mecrilate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption, Distribution, Metabolism, Excretion:

Alkyl 2-cyanoacrylates such as methyl 2-cyanoacrylate (MCA) are known to polymerize rapidly in the presence of water. Even the moisture in the surrounding, e.g. on the skin, is sufficient to start the polymerization process. As described by Krall et al., alkyl 2-cyanoacrylates "polymerize on and adhere to moist living tissues" (Krall, 1983). This effect triggered also the use of this substance class as tissue adhesives in medical applications.

Within seconds, a significant amount of the original MCA monomer forms a hardened mass. The formation of the polymer in the stomach after application via gavage was also described in the acute oral toxicity studies with MCA and the structural homologue ethyl 2-cyanoacrylate (ECA) (see also chapter 'acute toxicity'). This intrinsic property to polymerize in the presence of water limits the absorption of cyanoacrylates via all three routes (oral, dermal, inhalation).

Nevertheless, absorption after oral or dermal application was shown for acryl 2-cyanoacrylates in animal studies (Nordic Expert Group, 1997). It seems that over time, a part of the polymerized acryl 2-cyanoacrylate is being absorbed, probably due to degradation of the polymer. The absorption rate of MCA applied to oral rat mucosa was similar to that known for implanted MCA, i.e. approximately 1% per day (Ousterhout et al, 1969). So far, no information is available regarding absorption after inhalation or via the dermal route.

In comparison to the butyl 2 -cyanoacrylate (BCA) polymer, the percentage excreted via urine was much higher for the MCA polymer, indicating a faster turnover for MCA. Ousterhout et al. concluded that hydrolytic degradation of alkyl 2-cyanoacrylates could be the underlying mechanism, resulting in alkyl 2-cyanoacetate and formaldehyde (Ousterhout et al., 1969).

Compared to other alkyl 2-cyanoacrylates, MCA seems to be eliminated most rapidly (Nordic Expert Group, 1997). After application of MCA polymer via gavage, 33.7% of the original radioactivity was excreted within four days (urine: 15.9%, stool: 17.8%). On day four, the lowest excretion rate (0.1% for urine, 0.1% for stool) was observed (Ousterhout et al., 1969). The WHO suggested that 'the detection of radiolabel in the stool samples may well reflect the passage of poly-MCA particles directly through the gastrointestinal tract rather than any absorption and metabolism' (WHO, 2001).

After implantation of ¹⁴C-labelled acryl 2-cyanoacrylates under the skin of guinea pigs, radioactivity was detected in different organs, but decreased to base levels again. Other studies with rats did not detect radioactivity in organs, muscles or fat (Nordic Expert Group, 1997). Therefore, a bioaccumulation potential is not expected.

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

Nordic Expert Group, Scientific Basis for Swedish Occupational Standard XVIII - Consensus Report for Cyanoacrylates, Arbete och Hlsa, 25, 1997, pp. 17 -28

Osterhout D., Gladieux G.V., Wade C.W.R., Margetis P.M. and Leonard F., Digestive tract absorption of alkyl alpha-cyanoacrylate-beta-14C, O.S., O.M. & O.P., Vol. 27, No. 3, 1969, pp. 410-416

World Health Organization, Methyl Cyanoacrylate and Ethyl Cyanoacrylate, Concise International Chemical Assessment Document (CICAD) 36, Geneva, 2001; including corrigenda published by 12 April 2005