Enbucrilate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Enbucrilate

EC Number:

229-552-2

EC Name:

Enbucrilate

Cas Number:

6606-65-1

Molecular formula:

C8H11NO2

IUPAC Name:

butyl 2-cyanoprop-2-enoate

Test material form:

liquid

Details on test material:

Sterile applicator kits with an aliquot of LID-1187A (n-butylcyanoacrylate, CAS 6606-65-1, 97% a.i.), received at Life Science Research on 17 September 1990.
The test material, a pale yellow liquid, was further identified by the Batch No. 1577-19 and was kept in a refrigerator (approximately 4°C).

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, supplied by Ranch Rabbits, Crawley Down, Sussex, England were between 2.14 - 2.37 kg bodyweight on arrival and were approximately two and a half months of age. They were individually housed in suspended stainless steel cages (Type RC10/L) mounted in mobile batteries (Modular Systems and Development Co. Limited, landon, England). The cages measured 61 x 76 x 45 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly. Animals had free access to a commercially available standard pelleted rabbit diet (S.Q.C. Rabbit Diet, Special Diet 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 supplied to each cage by an automatie piped system. The water was supplied by the East Anglian Water Company to meet the World Health Organisation International Standard.
Reports from the local Water Authority recorded the chemical and bacteriological quality of the water. There was no information indicating that normal levels of common contaminants would influence the outcome of the study.

ENVIRONMENTAL CONTROL:

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 electriclty
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.

PRE-EXPOSURE PERIOD:

Each animal was inspected on arrival and unsuitable individuals were rejected. Individual bodyweight was recorded on the day of arrival and at regular intervals thereafter. All animals were identified by a uniquely numbered ear-tag within 24 hours of arrival. An acclimatisation period of seven to fourteen days was allowed between arrival at the laboratory and administration of the test material. During this time, the health status of each animal was monitored and a record kept. This record was consulted before an animal was allocated to study.
Twenty-four hours before dosing, the dorsum between the limb girdles was clipped (chemical depilatories were not used). Each animal was examined for abnormality or irritation of the dermal test site before allocation to study.
Each cage was labelled with details of the schedule number, ear-tag number, sex, route of administration, treatment level, Project licence number and responsible licensee.
Bodyweight on the day of dosing was within the range 2.46 - 2.82 kg. The rabbits were approximately three months old at this time.

Three acclimatised male rabbits were allocated to this study.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated test site

Amount / concentration applied:

single dose of 0.5mL of LID-1187A

Duration of treatment / exposure:

4 h

Observation period:

- 1, 24, 48 and 72 hours after removal of the dressings
- additional observations of persistent effects 6, 9, 12 and 15 days after administration

Number of animals:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1h

Score:

1

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1.3

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

1.3

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 6d

Score:

1.3

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 6

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 9d

Score:

1.7

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 7

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 12d

Score:

0.7

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 8

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 15d

Score:

0.7

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Results 9

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

0.3

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: all other time points edema score 0

Other effects:

- hard layer of test material over the test sites
- exfoliation

Any other information on results incl. tables

RESULTS

Very slight or well-defined erythema was observed at all test sites for nine days after treatment. Well-defined erythema persisted in one animal to termination.

Very slight oedema was observed at one test site 24 hours after bandage removal. Exfoliation was present at the test sites of the remaining two animals during the second week of the observation period.

A hard layer of test material was apparent over all three test sites during the first 72 hours following bandage removal; this was still present in one animal nine days after treatment. The dried test material did not affect the assessment of any erythematous response, but made it impossible to assess for loss of flexibility or elasticity of the test site.

The well-defined erythema with or without slight oedema observed at the edge of the test sites of two animals (Nos. 23TU 1784M and 23TU 1793M) is considered to have arisen from either the cracking of the test material and subsequent mechanical damage, or from the effects of grooming.

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

SCORING OF IRRITANCE RESPONSES

Animal	response	1h	24h	48h	72h	6d	9d	12d	15d
23TU1783M	erythema	1	1	1	1	2	2	0	0
	edema	0	0	0	0	0	0	0	0
	other	A	A	A	A			E
23TU1784M	erythema	1	1a	1a	1a	1a	1a	0	0
	edema	0	0	0	0	0	0	0	0
	other	A	A	A	A	AE	AE	E	E
23TU1793M	erythema	1	2	0b	2	1	2	2	2
	edema	0	1	0	0	0	0	0	0
	other		A	A	A

a: Small area (1x1cm) of exposed skin at base of site showing grade 2 erythema, grade 1 edema

b: Area at edge of test site showing grade 2 erythema

A: Hard layer of test material

E: Exfoliation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this test, direct application of LID-1187A was considered to be slightly irritant to intact skin.

Executive summary:

SUMMARY

The potential of LID-1187A to cause inflammatory or corrosive changes upon first contact with intact skin was assessed by direct, semi-occluded application of 0.5 mL of the test material to the closely-clipped dorsa of three New Zealand White rabbits. Dermal reactions were assessed 1, 24, 48 and 72 hours and six, nine, twelve and fifteen days after removal of the dressings.

Very slight or well-defined erythema was observed at the test sites of all animals during the first week or nine days after treatment. Very slight oedema was observed at one test site 24 hours after bandage removal; well-defined erythema was present at this site up to termination, fifteen days after treatment. Exfoliation was present at the test sites of the remaining two animals during the second week of the observation period. A hard layer of test material was apparent over all three test sites during the first 72 hours following bandage removal; this was still present in one animal nine days after treatment.

Under the conditions of this test, direct application of LID-1187A was considered to be 'slightly irritant' to intact skin.