Registration Dossier

Administrative data

Description of key information

Based on in vivo studies with ethyl 2-cyanoacrylate (ECA), the substance has to be classified as skin and eye irritant. Furthermore, evidence for respiratory irritation induced by methyl 2-cyanoacrylate exists from a study with human volunteers, and it is feasible to assign similar properties to ECA.


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
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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
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:
not specified
Amount / concentration applied:
0.5 g ethyl cyanoacrylate
Duration of treatment / exposure:
24 hours
Observation period:
The test areas were scored for dermal irritation immediately following the 24-hour exposure period and again at 72 hours.
Number of animals:
six male rabbits
Details on study design:
The skin on the dorsal surface of six male albino rabbits of theNew Zealand strain was shaved free of hair with an electric clipper. Twelve dorsal test areas were utilized; six of the dorsal test areas were abraded down to, but not through, the dermis, using a hypodermic needle. The reamining test areas were left intact. Standard patch test plasters (1" x 1" gauze pad) were saturated with 0,5g ethyl cyanoacrylat and applied to the dermal test areas. The patch test plasters were left in place for 24 hours. The test areas were scored for dermal irritation immediately following in the 24-hour expossure period and again at 72 hours.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
0.87
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
24 h
Score:
1.5
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Remarks:
intact skin
Basis:
mean
Time point:
72 h
Score:
0.16
Reversibility:
fully reversible
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
24 h
Score:
1.5
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
edema score
Remarks:
intact skin
Basis:
mean
Time point:
72 h
Score:
0.16
Reversibility:
fully reversible

 

Time of Observation [Hours]

Response Rabbit No.

Mean Score

 

 

1

2

3

4

5

6

 

Erythema & Eschar:

 

 

 

 

 

 

 

 

Intact Skin

24

2

2

1

1

1

2

1.50

Intact Skin

72

0

0

0

0

0

1

0.16

Abraded Skin

24

2

2

1

1

1

2

1.50

Abraded Skin

72

0

1

0

0

0

1

0.33

 

 

 

 

 

 

Subtotal:

3.49

Edema Formation:

 

 

 

 

 

 

 

 

Intact Skin

24

2

2

1

1

1

2

1.50

Intact Skin

72

0

0

0

0

0

1

0.16

Abraded Skin

24

2

2

1

1

1

2

1.50

Abraded Skin

72

0

1

0

0

0

1

0.33

 

 

 

 

 

 

Subtotal:

3.49

 

 

 

 

 

 

Total:

6.98

Interpretation of results:
other: slightly irritating
Conclusions:
The aim of this study was to investigate possible reversible or irreversible irritancy and/or corrosion by the test substance following a single application to the intact skin of rabbits.
Methods and investigations were performed in conformance with the OECD Guideline 404. A slight skin irritation was observed.
Executive summary:

The aim of this study was to investigate possible reversible or irreversible irritancy and/or corrosion by the test substance following a single application to the intact skin of rabbits. Methods and investigations were performed were similar to the procedure described in the OECD Guideline 404. An amount of 0.5 g ethyl-2-cyanoacrylate was applied to intact skin areas and to abraded skin areas (covered with an gauze bandage) of each of 6 rabbits. The duration of the exposure was 24 hours.The skin was examined directly after the 24 -hour exposure and 72 hours after patch removal. The primary dermal irritation index (PDII) was found to be 0.87 (includes scores for intact and abraded skin).

A slight skin irritation was observed.

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
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 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
0.1 ml of ethyl cyanoacrylate
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
24, 48 and 72 hours after instillation of ethyl cyanoacrylate
Number of animals or in vitro replicates:
9 male rabbits
Details on study design:
A dosage of 0.1 ml of ethyl cyanoacrylate was introduced into the conjunctival sac of the right eye of each rabbit; the left eye served as an untreated control.
The nine treated rabbit eyes were scored against the corresponding untreated control eyes at 24, 48 and 72 hours after instillation of ethyl cyanoacrylate.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
29.33
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Score:
15.33
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
9.66
Reversibility:
not specified
Remarks:
72h observation period
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24 h
Score:
1.44
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
48 h
Score:
1
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
0.56
Reversibility:
not specified
Remarks:
72h observation period
Irritation parameter:
iris score
Basis:
mean
Time point:
24 h
Score:
0.78
Irritation parameter:
iris score
Basis:
mean
Time point:
48 h
Score:
0.44
Irritation parameter:
iris score
Basis:
mean
Time point:
72 h
Score:
0.22
Reversibility:
not specified
Remarks:
72h observation period
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24 h
Score:
2.33
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
48 h
Score:
1.11
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
72 h
Score:
0.66
Reversibility:
not specified
Remarks:
72h observation period
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24 h
Score:
2.11
Irritation parameter:
chemosis score
Basis:
mean
Time point:
48 h
Score:
0.56
Irritation parameter:
chemosis score
Basis:
mean
Time point:
72 h
Score:
0.22
Reversibility:
not specified
Remarks:
72h observation period

 

 

Rabbit number

 

Hours

 

1

2

3

4

5

6

7

8

9

Group Mean Score

24

I. Cornea

 

 

 

 

 

 

 

 

 

 

a. Opacity

1

2

1

2

2

1

1

1

2

 

b. Area Involved

1

2

1

2

2

1

1

1

2

 

II. Iris

 

 

 

 

 

 

 

 

 

 

a. Evaluation

0

2

1

1

1

0

1

0

1

 

III. Conjunctiva

 

 

 

 

 

 

 

 

 

 

a. Hyperemia

1

3

2

3

3

3

2

2

2

 

b. Chemosis

1

3

1

3

3

3

2

1

2

 

C. Discharge

2

3

2

3

3

3

2

2

2

 

Total Score

13

48

20

43

43

23

22

15

37

29.33

 

 

 

 

 

 

 

 

 

 

 

 

48

I. Cornea

 

 

 

 

 

 

 

 

 

 

a. Opacity

0

2

0

3

1

1

1

0

1

 

b. Area Involved

0

2

0

2

1

1

1

0

1

 

II. Iris

 

 

 

 

 

 

 

 

 

 

a. Evaluation

0

1

0

1

0

1

0

0

1

 

III. Conjunctiva

 

 

 

 

 

 

 

 

 

 

a. Hyperemia

0

2

1

2

1

1

1

1

1

 

b. Chemosis

0

1

1

2

0

1

0

0

0

 

C. Discharge

1

2

1

3

1

2

1

1

2

 

Total Score

2

35

6

39

9

18

9

4

16

15.33

 

 

 

 

 

 

 

 

 

 

 

 

72

I. Cornea

 

 

 

 

 

 

 

 

 

 

a. Opacity

0

2

0

2

0

0

0

0

1

 

b. Area Involved

0

2

0

2

0

0

0

0

1

 

II. Iris

 

 

 

 

 

 

 

 

 

 

a. Evaluation

0

0

0

1

0

0

0

0

1

 

III. Conjunctiva

 

 

 

 

 

 

 

 

 

 

a. Hyperemia

0

2

0

2

0

1

0

0

1

 

b. Chemosis

0

0

0

2

0

0

0

0

0

 

C. Discharge

0

2

0

3

0

1

0

0

2

 

Total Score

0

28

0

39

0

4

0

0

16

9.66

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The aim of this study was to investigate possible reversible or irreversible irritancy by the test substance following a single application into the eyes of rabbits.
Methods and investigations were performed in conformance with the OECD Guideline 405. An irritation was observed.
Executive summary:

The aim of this study was to investigate possible reversible or irreversible irritancy by the test substance following a single application into the eyes of rabbits. The procedure followed in principle the standard that was later described in the OECD Technical Guideline 405. For the test,0.1 mL ethyl 2-cyanoacrylate was applied into the conjunctival sac of the right eyes of each of the 9 rabbits. The duration of the exposure was 72 hours. The treated rabbit eyes were investigated after 24, 48 and 72 hours after instillation of ethyl 2-cyanoacrylate. The group mean score at 24 hours was 29.33. the group mean score at 48 and 72 hours were 15.33 and 9.66 respectively. An irritation was observed.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Skin irritation:

In an OECD 404 guideline study with New Zealand rabbits a slightly irritating property of ethyl 2-cyanoacrylate was shown with a primary dermal irritation index (PDII) of 0.87 (mean). Furthermore, severe dermal irritation is typically not reported in cases of human exposure. Hence, ethyl 2-cyanoacrylate is not considered to be skin irritating. However, based on CLP Regulation (EC) No 1272/2008, Annex VI, Table 3, ethyl 2-cyanoacrylate requires classification as Skin Irrit. 2. H315.

Eye irritation:

Ethyl 2-cyanoacrylate was tested in an OECD 405 guideline study resulting in in an overall irritation score of 29.33 (mean) with reversibility within 24 hours. Based on this study, ethyl 2-cyanoacrylate is considered eye irritating and classified as Eye Irrit. 2, H319.

 

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 high structural and physicochemical similarity to ethyl 2-cyanoacrylate (ECA) and in view of the overall irritating properties of ECA, it is considered that ECA also exerts respiratory irritation. Correspondingly, it is classified as STOT SE 3, H335.