2-methoxyethyl 2-cyanoacrylate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May - June 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The dermal test area was larger than that normally used in this type of study because of the physical properties of the test material.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Propenoic acid, 2-cyano-, 2-methoxy-1-methylethyl ester

Cas Number:

27279-62-5

Molecular formula:

C8H11NO3

IUPAC Name:

2-Propenoic acid, 2-cyano-, 2-methoxy-1-methylethyl ester

Test material form:

liquid

Details on test material:

- Name: ß-methoxy-iso-propyl cyanoacrylate, referred to as MPCA
- Synonym: 2-Propenoic acid, 2-cyano-, 2-methoxy-1-methylethyl ester
- Formula: C8-H11-N-O3
- Molecular weight: 169.2 g/mol
- CAS 27279-62-5
- Sample Ref. No.: 1696-36
- Appearance: clear colourless liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS AND HUSBANDRY
Young albino rabbits of an outbred New Zealand White strain were supplied by Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England, They were individually housed in suspended stainless steel cages (Type TR6) mounted in mobile batteries (Modular Systems and Development Company Limited, London, England). The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent paper which was changed regularly.
Animals had free access to a commercially available standard pelleted rabbit diet (S,Q,C. Rabbit Diet, Special Diets Services Limited, Witham, Essex, England). The manufacturer supplied analytical data with each batch of diet. This included the concentrations of nutritional components , aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment.
The rabbits had free access to tap water taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations. Certificates of analysis were routinely received from the supplier (Suffolk Water Company). At approximately six-month intervals water was routinely sampled for analysis, by a laboratory independent of the supplier, for selected chlorinated and organophosphorous pesticides, polychlorinated biphenyls and lead and cadmium contaminants; it was also examined for coliform bacteria. Results of these analyses are retained in the archives.
There was no information indicating that normal levels of common contaminants, or specific contaminants, in the diet or drinking water would influence the outcome of the study,

ENVIRONMENTAL CONDITIONS
The animals were housed in a lagomorph room within a limited-access building. The room was kept at slight positive pressure relative to the outside and had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation.
Target values for temperature and humidity were 18°C (range 15°-23°C) and 55% R.H. (range 40%-70% R.H.), respectively. The achieved values were monitored daily. Electric time-switches operated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of apower failure.
All personnel entering the building changed into clean protective clothing and wore a gown, plastic over-shoes, gloves and a face mask to service the rabbit-holding areas,

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: The right test site acted as a control and remained untreated.

Amount / concentration applied:

single dose of 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h after removal of the bandages
Additional observations of persistent effects of treatment were made 6, 9, 12 and 15 days after treatment.

Number of animals:

3

Details on study design:

The potential of Methoxy-iso-propyl cyanoacrylate, to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 mL of the test material to the closely-clipped dorsa of three New Zealand White rabbits for four hours. The test material was spread evenly over a 5 x 6 cm area of the exposed skin and allowed to dry be fore bandaging. The test site was protected by an Elizabethan collar for a period of 48 hours after removal of the bandage and dermal reactions assessed after 1, 24, 48 and 72 hours and six, nine, twelve and fifteen days after bandage removal .

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Any other information on results incl. tables

Very slight erythema with or without very slight oedema was oberved at the test site of each animal throughout the first 72 hours after removal of the dressings. Three days later, very slight erythema and oedema were evident in one animal only, resolving by the twelfth day after treatment. Since the test material spread and dried as a fine hard film, the observations were made at the edges. Although the film appeared to be clear, it was difficult to be sure of the condition of the underlying skin. However, it was considered that the reactions, if any, were no worse than those at the margins of the film. The film had begun to crack in one animal 24 hours after bandage removal and in the other animals eight days later. The majority of the film on each test site was still present at termination.

When the collars were removed one animal was immediately observed grooming the test site; the other two animals interfered with the solid film during the latter part of the first week of examination. The areas of test material removed in this way varied from 1 x 1 cm to 6 x 2 cm with damage done to the uppermost skin layer only; foci of eschar formation were evident on these areas. The majority of the damage occurred during the first five days after collar removal, but some occurred during the following week.

The control sites did not show any response to the control procedure.

The mean values for erythema and oedema recorded 24, 48 and 72 hours after treatment did not equal or exceed the EEC limit values considered to indicate a significant inflammatory response to treatment.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the criteria of the EEC, MPCA was classified as non-irritant to the skin.

Executive summary:

Under the criteria of the EEC, MPCA was classified as non-irritant to the skin. However, the test material clearly exerted a local effect which caused the animals to try to remove the solid layer, resulting in secondary damage. It is considered that the neck collars prevented interference during the first 48 h after treatment, thereby reducing the degree of this secondary damage. However, the mean values for erythema and oedema recorded 24, 48 and 72 hours after treatment did not equal or exceed the EEC limit values considered to indicate a significant inflammatory response to treatment.