Mecrilate

Endpoint summary

Description of key information

All available data on methyl 2-cyanoacrylate (MCA) and the structural homologue 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study meets generally accepted scientific principles, but was not conducted in compliance with GLP or an OECD testing guideline.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

no

Remarks:

prior to GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Albino

Sex:

male

Details on test animals or test system and environmental conditions:

6 male albino rats fasted for 18 hours prior to dosing.
The initial body weights ranged from 195 to 221 grams.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

The animals were observed during the day of dosing and daily thereafter for 14 days.
Decedents during the study were examined for gross lesions.

Statistics:

no

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 440 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: 88.8 % ai

Mortality:

None (0/6)

Clinical signs:

other: Pilo-erection, lethargy

Gross pathology:

Caecum slightly enlarged , blood vessels of stomach, caecum and intestines were injected; large hardened mass of the test material of approximately the same size and shape of the stomach was found in the stomach of each animal sacrificed. However, no ulcers were observed in the stomach.

Other findings:

None

RESULTS

Onset of signs (S):

0 - 4 h	4 - 8 h	8 - 24 h
6 S	-	-

Mortaliy (M) and Recovery (R):

day 2	day 3	day 4	day 5	day 6	days 7 - 14
-	-	-	3 R	3 R	-

Caecum slightly enlarged, blood vessels of stomach. caecum and intestines were injected; large hardened mass of the test material of approximately the same size and shape of the stomach was found in the stomach of each animal sacrificed, however, no ulcers were observed in the stomach and no loss of body weight occurred in any of the animals during the 14-day period of observation.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was found to be greater than 5000 mg/kg bw (greater than 4400 mg/kg bw relating to methyl 2-cyanoacrylate). In conclusion, the test material can be considered as practically nontoxic.

Executive summary:

In a limit test with 6 male Albino rats, 5000 mg/kg bw of the Loctite glue "150 Super Bonder" was administered by gavage. All animals exhibited signs of intoxication (pilo-erection, lethargy), which were reversible within 5-6 days. No mortality was observed during the 14 -day observation period. Therefore, the LD50 for the tested material has been identified as > 5000 mg/kg bw (corresponding to 4400 mg/kg of the active ingredient methyl 2 -cyanoacrylate).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

See discussion.

Acute toxicity: via inhalation route

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:

read-across from supporting substance (structural analogue or surrogate)

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)

Justification for type of information:

Justification: Ethyl 2-cyanoacrylate (ECA) is a structural homologue that contains an additional CH2-group (see attached justification).

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality

Gross pathology:

.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

See discussion.

Additional information

Acute oral toxicity:

Two acute oral toxicity studies with comparable test design, and similar to the limit test as described in OECD TG 423, are available. Both assays were performed under non-GLP conditions. One of the studies was conducted with methyl 2-cyanoacrylate (MCA, the substance to be registered), the other with ethyl 2-cyanoacrylate (ECA), a structural homologue that contains an additional CH₂-group. In both studies, 5000 mg/kg of the test substance 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.

In the study with MCA, pilo-erection and lethargy was observed in all rats. These signs of intoxication were reversible within 5 -6 days. The gross pathology exhibited the following findings: Caecum slightly enlarged, blood vessels of stomach, caecum and intestines were injected; large hardened mass of the test material of approximately the same size and shape of the stomach was found in the stomach of each animal sacrificed. However, no ulcers were observed in the stomach.

Due to the intrinsic of cyanoacrylates to form polymers in the presence of water, both MCA and ECA polymerized in the stomach, which resulted in the formation of a hardened mass.

In the test with ECA, one animal died on day 4. 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. Food in intestines as in a normal rat. One rat had dilated intestinal blood vessels.

In conclusion, the tests with the substance to be registered (MCA) and the close homologue (ECA) gave no indication for an acute toxic potential after oral application. LD₅₀ values of >5000 mg/kg bw were therefore deviated in both tests. In the case of the key study, the percentage of MCA in the test material has to be taken into account, resulting in an LD₅₀ value of >4400 mg/kg bw. Since no animal died in the test with MCA at this dose level, it can be expected that the LD₅₀ also surpasses the value of 5000 mg/kg bw.

Acute inhalation toxicity:

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

- Exposure: Methyl-2-cyanoacrylate (MCA) 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 MCA 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 MCA/the close homologue ECA as well as the human experience with glues containing cyanoacrylates, no indication exists to assume an acute toxic potential of MCA 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. The close homologue ethyl 2-cyanoacrylate (ECA) was used as test material. 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 effect 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 the close homologue ECA to rabbits. In light of this result, and taking into account the oral LD₅₀ of 4400 mg/kg obtained in a study with MCA as well as the fact that immediate polymerization limits the dermal uptake of MCA, it can be concluded that MCA is not suspected to induce acute dermal toxicity.

Justification for selection of acute toxicity – oral endpoint
See discussion.

Justification for selection of acute toxicity – dermal endpoint
See discussion.

Justification for classification or non-classification

See discussion.