Enbucrilate

Endpoint summary

Description of key information

- REACH_LD50 > 5000 mg/kg bw  | rat (male/female) | OECD 423 | ethyl-2cyanoacrylate #key study##Analogy# 
- REACH_negative | mouse (male) | other: ISO 10993-11, Systemic Injection Test | Indermil

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Additional information

Butyl cyanoacrylate is a structural analogue to 2-ethyl cyanoacrylate. Both substances share the reactive cyanoacrylate function. The chain length of the alcohol moiety in butyl cyanoacrylate is slightly increased compared to 2-ethyl cyanoacrylate. The mentioned cyanoacrylates are very reactive monomers and polymerize immediately (within 30-60 sec) in the presence of moisture based on the same reaction mechanism. The polymerized materials have a high molecular mass and are not able to penetrate through skin or intestinal wall resulting in low bioavailability. Based on this physico-chemical behaviour, conducting an experimental test for assessing the acute oral toxicity of the monomer is technically not meaningful. Thus, it is concluded that for butyl cyanoacrylate data on acute oral toxicity can be drawn from the structural analogue 2-ethyl cyanoacrylate.

 

It was the aim of the study with 2-ethylcyanoacrylate to investigate acute toxic effects of the test substance after a single oral administration.

 

Methods

The method was similar to the OECD-Guideline 423, "Acute Oral Toxicity - Acute Toxic Class Method".

Administration: Ethyl-2-cyanoacrylate was administered once orally by stomach intubation to 6 male albino rats (5000 mg/kg).

Investigations: The animals were observed during the day of dosing and daily thereafter for 14 days.

Necropsy: all animals were sacrificed and necropsied 14 days p.a.

 

Results

Mortality: One mortality was observed.

Necropsy findings: The pathological examination showed hemorrhagic lungs, a solid mass in stomach, not adhered to stomach wall but too large to pass through pyloric valve. Cardiac portion of stomach distended. Food in intestines as in a normal rat. One rat had dilated intestinal blood vessels.

The LD50 of ethyl-2-cyanoacrylate is estimated to be higher than 5000 mg/kg body weight in rats for a single dose.

Moreover, in a test according to ISO 10993-11 (1993), Biological Evaluation of Medical Devices Part 11: Test for Systemic Toxicity, it was observed that extracts of the cured, polymerized material did not induce a significantly greater biological reaction than the control articles, when tested in Albino Swiss mice after intraveneous or intraperitoneal injection.

 

Based on the overall weight of evidence, n-butyl cyanoacrylate is considered to be of low acute toxicity after oral exposure.

Justification for classification or non-classification

Butyl cyanoacrylate will polymerize quickly in contact with water resulting in low bioavailability. Based on the fact that the structural analogue 2-ethyl cyanoacrylate has shown an LD50 of > 5000 mg/kg body weight in an experimental investigation (oral, rat) and the reaction mechanism is the same for butyl cyanoacrylate, it is concluded that butyl cyanoacrylate will also not be of acute oral toxicity and is thus not classified.