Mecrilate

Endpoint summary

Description of key information

Based on in vivo studies with methyl 2-cyanoacrylate (MCA) and the structural homologue ethyl 2-cyanoacrylate (ECA), MCA has to be classified as skin and eye irritant. Furthermore, evidence for respiratory irritation induced by MCA exists from a study with human volunteers.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no GLP)

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations § 191.11 (1973)

GLP compliance:

no

Remarks:

prior to GLP

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: clipped; 6 areas abraded, 6 areas intact skin

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

72 h

Number of animals:

6

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Remarks:

Erythema & Eschar

Basis:

mean

Remarks:

intact skin

Time point:

24 h

Score:

1.17

Max. score:

2

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

Erythema & Eschar

Basis:

mean

Remarks:

intact skin

Time point:

72 h

Score:

0.33

Max. score:

1

Reversibility:

no data

Irritation parameter:

erythema score

Remarks:

Erythema & Eschar

Basis:

mean

Remarks:

abraded skin

Time point:

24 h

Score:

2.17

Max. score:

3

Reversibility:

not fully reversible within: 72 h

Irritation parameter:

erythema score

Remarks:

Erythema & Eschar

Basis:

mean

Remarks:

abraded skin

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

no data

Irritation parameter:

edema score

Basis:

mean

Remarks:

intact and abraded skin

Time point:

other: 24/72 h

Score:

0

Max. score:

0

Remarks on result:

other: no edema observed

RESULTS

The individual scores with regard to Erythema and Eschar formation for each rabbit in this study are presented in TABLE 1. No edema formation has been observed throughout the study.

Mean scores are totaled and averaged to provide an arbitrary Primary Irritation Index (PII) . For the sample identified as 150 Super-Bonder , the PlI was found to be 1.92. According to the evaluation of Draize, the 150 Super- Bonder would be considered an irritant to the skin.

TABLE 1 (Erythema & Eschar)

Preparation	time of observation	1	2	3	4	5	6
intact skin	24 h	2	1	1	1	1	1
intact skin	72 h	1	0	1	0	0	0
abraded skin	24 h	3	2	3	2	1	2
abraded skin	72 h	4	4	4	4	4	4

Remark:

After the 24 h exposure period, the test pIasters were bonded to the skin and could not be removed without damage to the skin. The skin immediately surrounding the bandages appeared hard and irritated and at 72 h slight eschar formation was observed.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

According to the evaluation of Draize, the test material would be considered an irritant to the skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions (no GLP)

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations § 191.12 (1973)

GLP compliance:

no

Remarks:

prior to GLP

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

6

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

1.33

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

1.25

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

1.17

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

1.33

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Score:

0.5

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

0.67

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2.33

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

2.25

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

1.67

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1.33

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0.83

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

33

Remarks on result:

other: 3 rabbits only due to bonded lids

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

28.2

Remarks on result:

other: 4 rabbits only due to bonded lids

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

32.5

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

27.5

RESULTS

The individual scores for each rabbit in this study are presented in TABLE 1. The group mean score at 24 hours was 33.0. The group mean scores at 48 and 72 hours and 7 days were 28.2, 32.5 and 27.5 respectively. According to the Draize evaluation, 150 Super-Bonder would be considered an irritant to the eye.

TABLE 1

time	parameter	1	2	3	4	5	6	mean
24 h	cornea - opacity	*	0	3	*	1	*	1.33
24 h	cornea - area	*	0	3	*	1	*	1.33
24 h	iris	*	0	3	*	1	*	1.33
24 h	conjunctiva - hyperemia	*	2	2	*	3	*	2.33
24 h	conjunctiva - chemosis	*	1	1	*	2	*	1.33
24 h	conjunctiva - discharge	*	0	3	*	3	*	2.00
48 h	cornea - opacity	0	0	3	*	2	*	1.25
48 h	cornea - area	0	0	3	*	2	*	1.25
48 h	iris	0	0	1	*	1	*	0.50
48 h	conjunctiva - hyperemia	3	1	2	*	3	*	2.25
48 h	conjunctiva - chemosis	1	0	1	*	2	*	1.00
48 h	conjunctiva - discharge	2	1	1	*	2	*	1.50
72 h	cornea - opacity	0	0	0	3	0	4	1.17
72 h	cornea - area	0	0	0	3	0	4	1.17
72 h	iris	0	0	0	2	0	2	0.67
72 h	conjunctiva - hyperemia	1	1	2	2	2	2	1.67
72 h	conjunctiva - chemosis	0	0	0	3	0	2	0.83
72 h	conjunctiva - discharge	1	1	1	3	1	3	1.67
7 d	cornea - opacity	0	0	0	4	0	3	1.17
7 d	cornea - area	0	0	0	4	0	3	1.17
7 d	iris	0	0	0	2	0	2	0.67
7 d	conjunctiva - hyperemia	0	0	0	1	0	2	0.50
7 d	conjunctiva - chemosis	0	0	0	3	0	2	0.83
7 d	conjunctiva - discharge	0	0	0	1	0	1	0.33

1 -3 unwashed, 4 -5 2 -sec. rinse

* lids bonded shut

Remark:

The initial reaction of each rabbit as the compound was introduced into the eye was one of severe irritation characterized by a vocalization of pain. In almost all instances, the lids of each rabbit were bonded shut but only those which were more easily forced open were gently pried open to make the readings. No attempt was made to forcibly pry or cut open the lids which were strongly bonded so that any unnecessary damage to the eye was avoided. In all cases where the eye was severely irritated, a white pus-like discharge was observed. Photographs of the described observations were taken at various intervals during the study.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Remarks:

Criteria used for interpretation of results: Draize

Conclusions:

According to the Draize evaluation, the test material would be considered an irritant to the eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation:

The skin irritation potential of methyl 2-cyanoacrylate (MCA) was tested in an in vivo study with six rabbits. The test was conducted according to the Draize protocol, with certain deviations from today's OECD TG 404. While the test item should be applied on intact skin (OECD TG 404), both intact and abraded skin was tested in the study with MCA. The incubation was 24 h under occlusive conditions, whereas 4 h and semi-occlusive conditions are standard today. In sum, the conditions of the experiment with MCA were stricter. Furthermore, it is reported that "after the 24-hour exposure period, the test plasters were bonded to the skin and could not be removed without damage to the skin", implying that the observed skin lesions were partly induced during handling and can not necessarily be attributed to the skin irritation potential of the substance. The scores determined in the case of the intact skin point to a mild skin irritation potential. However, the observation period was shorter as requested by OECD TG 404, and scores were noted only at two time points (directly after removal of the patch, and 72 h later). Therefore a clear distinction between Skin Irrit. 2 and 3 is not feasible on the basis of this test. In addition, no definite statement can be made whether the observed effects would persist until day 14 after removal of the patch. Similar results were obtained in a study with the close homologue ethyl 2-cyanoacrylate (ECA) that followed the same protocol. Evidence for a rather strong than mild irritation potential comes from a study with MCA of which a short summary is published (Bomhard et. al, Acute Toxicologic Evaluation of Methylcyanoacrylate, International Journal of Toxicology, Vol. 16, Supplement 2, 1997, p. 40). The study seems to follow a rather modern protocol (semi-occlusive patch, 4 h exposure period, evaluation 1 h / 24 h / 48 h / 72 h / 7 d / 14 d after patch removal). On a weight-of-evidence basis, it is concluded that MCA should be classified as Skin Irrit. 2.

Eye irritation:

An in vivo study conducted with MCA revealed an eye irritation potential of the substance. The study followed in principle the standard of OECD TG 405, which was not existent at the time of the test. Though technical problems were observed - lids were bonded shut by the substance - an evalulation of eye irritation effects was feasible. Of the nine rabbits, at least three could be evaluated per time point. According to the scores determined in this test, MCA has to be classified as Eye Irrit. 2. Further evidence for this classification was obtained by a similar test with the structural homologue ethyl 2-cyanoacrylate (ECA). Though a certain reversibility was observed in both tests with MCA and ECA, the observation period was too short to conclude that the effect induced by MCA would not be persistent. Evidence for reversibility of effects comes from an unpublished study cited in the report of the German MAK commission. After application of one drop of a technical-grade adhesive which consisted primarily of MCA, adhesions of the lids, irritation of the conjunctiva and staining of the cornea was observed. The effects were reversible within 14 days (The MAK Collection for Occupational Health and Safety, Cyanacrylsäuremethylester, Cyanacrylasäure-Äthylester, MAK Value Documentation in German language, 1979, published online 31 January 2012). Altogether, the available data suggest that MCA has to be classified as Eye Irrit. 2.

Respiratory irritation:

In a study from 1968, fourteen volunteers were exposed to vapour concentrations of appr. 1-60 ppm MCA. Irritation of nose and throat started at 2 ppm MCA, irritation and burning in eyes at 4 ppm. For high concentrations in the range of 50 -60 ppm, pronounced irritation of eyes and nose was reported (McGee et al., Am. Ind. Hyg. Assoc. J., 1968 (29), 558 -561). Based on the general irritation potential of MCA that was observed in skin and eye irritation studies and on human data, MCA needs to be classified with regard to respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:
See discussion.

Justification for selection of eye irritation endpoint:
See discussion.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

See discussion.