Registration Dossier

Administrative data

Description of key information

All available data on ethyl 2-cyanoacrylate (ECA) indicate an absence of lethal effects after application of doses >2000 mg/kg body weight via the oral or dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (no GLP)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: the body weight ranged from 206 to 246 g
- Fasting period before study: 18 hours
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
No. of animals per sex per dose:
6 male albino rats
Control animals:
no
Details on study design:
The test compound was administered by oral intubation to 1 group of 6 male albino rats fasted for 18 hours prior to dosing. The animals were observed during the day of dosing and daily thereafter for 14 days. Decents during the study were examined for gross lession.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
One rat died on the fourth day.
Gross pathology:
Hemorrhagic lungs. solid mass in stomach, not adhered to stomach wall but too large to pass through pyloric valve. Cardic portion of stomach distended. Food in intestines as in a normal rat. One rat had dilated intestinal blood vessels.
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of ethyl-2-cyanoacrylate is estimated to be higher than 5000 mg/kg body weight in rats for a single dose.
Therefore the test substance ethyl-2-cyanoacrylate can be considered practically nontoxic according to the EC Guideline 93/21.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
See discussion

Acute toxicity: via inhalation route

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

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (no GLP)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: weight ranged from 2034 to 2481 g
- Housing: cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The rabbits were clipped free of dorsal hair with an electric clipper. The test material were applied under rubber dental damming held in place with adhesive tape.
Duration of exposure:
24 hours
Doses:
no data
No. of animals per sex per dose:
4 male albino rabbits of the New Zealand strain
Control animals:
no
Details on study design:
The rabbits were clipped free of dorsal hair with an electric clipper. The test material were applied under rubber dental damming held in place with adhesive tape for 24 hours. During this time, the animals were observed for signs of systemictoxicity.
Observations for mortality and signs of effect were made for 14 days, and the survivors were sacridiced and examined for gross pathology.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Gross pathology:
.
Other findings:
Bandages and wrapping were initially bonded to sskin; however, after 14 days, bandages were easily peeled off exposing a large open sore at the site of application.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of ethyl-2-cyanoacrylate is estimated to be higher than 2000 mg/kg body weight in rabbits for a single dose.
Therefore the test substance ethyl-2-cyanoacrylate is practically nontoxic according to the EC Guideline 93/21.
Executive summary:

In an acute dermal study similar to OECD TG 402, a limit dose of 2000 mg/kg bw ethyl 2 -cyanoacrylate was administered once on the dorsal free clipped skin of four male albino rabbits. The animals were observed during the day of dosing and daily thereafter for 14 days.On day 14, all animals were sacrificed and necropsied. No mortality was observed during the study. A large open sore was observed after 14 days of exposre. The dermal LD50 of ethyl 2 -cyanoacrylate was estimated to be higher than 2000 mg/kg bw in rabbits after single exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity:

An acute oral toxicity study similar to the limit test as described in OECD TG 423 is available. The study was performed under non-GLP conditions. 5000 mg/kg of ethyl 2 -cyanoacrylate (ECA) was applied by gavage to 6 male albino rats fasted for 18 hours prior to dosing. The animals were observed during the day of dosing and daily thereafter for 14 days. Furthermore, the number of deaths, any signs of intoxication and the results of pathological examinations were protocolled.

For one animal that died during the study period, the following gross pathology findings were observed: Hemorrhagic lungs; solid mass in stomach, not adhered to stomach wall but too large to pass through pyloric valve; Cardic portion of stomach distended. Formation of a hardened mass in the stomach is a result of the intrinsic property of ECA to polymerize in the presence of water. Death of the animal is considered secondary to the building of the polymerized mass in the stomach.

In conclusion, the test gave no indication for an acute toxic potential after oral application. A LD50 value of >5000 mg/kg bw was therefore derived from the test.

Acute inhalation toxicity:

An acute inhalation toxicity test was omitted for the following reasons:

- Exposure: Ethyl-2-cyanoacrylate (ECA) polymerizes immediately in the presence of water, the moisture in the surrounding air is sufficient to start the process. For this reason, inhalation exposure to the ECA monomer plays a minor role.

- Technical feasibility: The rapid polymerization would also make inhalation experiments technically not feasible. Therefore, the acute inhalation study can be waived according to REACH Annex XI section 2. In the ECHA guidance (chapter R.5, version 2.1 of December 2011), the example of a substance having a high reactivity with water is explicitly cited as a case where testing is technically not feasible.

- Evidence: Taking into account the available acute oral/dermal studies with ECA as well as the human experience with glues containing cyanoacrylates, no indication exists to assume an acute toxic potential of ECA after inhalation contact.

Acute dermal toxicity:

An acute dermal toxicity study similar to OECD TG 402 was conducted with 4 male albino rabbits of the New Zealand strain. After removal of dorsal hair with an electric clipper, the test material was applied under rubber dental damming held in place with adhesive tape. During the exposure time of 24 hours, the animals were observed for signs of intoxication. Observations for mortality and signs of effects were made for 14 days, and the survivors were sacrificed and examined for gross pathology. It was noticed that bandages and wrapping which had initially been bonded to skin were easily peeled off after 14 days, exposing a large open sore at the site of application. No mortality and no other signs of toxicity were observed, leading to the conclusion that an LD50 value of >2000 mg/kg could be assumed after dermal application of ethyl 2 -cyanoacrylate to rabbits.


Justification for classification or non-classification

Based on studies on acute oral and dermal toxicity which result in LD50 values of greater than 5000 mg/kg bw and 2000 mg/kg bw, respectively, and due to the fast polymerization in the presence of water, ethyl 2-cyanoacrylate is considered non acute toxic via oral, dermal and inhalation route. Accordingly, no classification is required.