Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27.03.1984 - 30.03.1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Well documented study but exposure time 24 h instead of 4h hours and observation time only 72 hours instead of 14 days.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Journal officiel de la Republique Francaise, 21 February 1982
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source Nottingham University, School of Agriculture, Sutton Bonington, Leics & Rosemead Rabbits Ltd., Lea Valles, Essex
- Age at study initiation: 12-16 weks
- Weight at study initiation: 2.78-3.10 kg
- Housing: All animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory (rabbit diet, A.W. Tindall Limited, Holbeach, Lincolnshire)
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 +/- 2.5 °C
- Humidity (%): 52-58 %
- Air changes (per hr): 10 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Test system

Type of coverage:
occlusive
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
1 hour following removal of the patches and 48 hours later (72 hours after application of test material)
Number of animals:
6
Details on study design:
Approximately twenty-four hours prior to the commencement of the test each of a group of six rabbits were prepared by closely clipping the hair from the dorsal/flank areas using Oster A5 professional animal clippers (size 40 cutters). Immediately before treatment on the day of the test the right side of each rabbit was abraded using the tip of a scalpel blade. Abrasion consisted of superficial skin injury sufficient to disturb the stratum corneum but not deep enough to cause bleeding. The left side of each rabbit remained intact.
A 0.5 ml aliquot of the test material was introduced under a composite patch which consisted of a 2.5 cm x 2.5 cm square of absorbant lint BPC backed by a 4.0 cm x 4.0 cm square of absorbant lint BPC with a final backing of a 3.0 cm x 3.0 cm square of polythene. The patches were applied to the abraded and intact test sites of each animal and held securely in position by two lengths of Sleek adhesive strapping (Smith & Nephew Limited) in the form of a cross. An elasticated corset was then applied (Seton's Tubigrip) to prevent interference with the patches. The rabbits were then returned to their cages where they could move about, eat and drink normally.
Twenty-four hours later the corset was removed from each animal and the patches were carefully taken off the test sites. Any residual test material was removed by gentle swabbing with cotton wool soaked in lukewarm water or other suitable solvent. Approximately one hour following removal of the patches and 48 hours later (i.e 72 hours after the test material was applied) the intact and abraded sites of each animal were observed for evidence of irritation. Reactions were scored according to i.e Draize J.H (1959) Association of Food & Drug Officials of the USA, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24+72 h
Score:
2.17
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24+72 h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: shaved skin

Any other information on results incl. tables

Skin reaction

Skin site

Readings

(hours)

Individual scores

Total

 Rabbit number

1

2

3

4

5

6

 

Erythema and Eschar formation

Intact

24

2

3

2

2

2

2

13

 

72

1

2

3

3

2

2

13

Abraded

24

2

3

2

2

2

2

13

 

72

2

2

3

3

2

3

15

Oedema Formation

Intact

24

4

4

4

4

4

2

22

 

72

2

1

1

2

1

1

8

Abraded

24

4

4

4

4

4

2

22

 

72

2

2

1

2

1

1

9

 

Group total score

115

Primary irritation index: Group total score/24 = 4.8

 

Reevaluation according GHS criteria

Only animals with shaved skin were evaluated

 

 

Erythema

Edema

Animal No.

24 h

72h

24h

72h

1

2

1

4

2

2

3

2

4

1

3

2

3

4

1

4

2

3

4

2

5

2

2

4

1

6

2

2

2

1

Mean value

2.166

2.5

 

 

Classification according GHS: Category 2 (Erythema < 2,3; Edema > 2,3)

 

Remark:

Exposure time: 24 hours instead of 4 hours

Study was too short for a clear statement of reversibility because there was no observation after 72 hours.

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In this study methacrylic anhydride was irritating to skin, GHS/OECD criteria Catregory 2. However the exposure time was 24 h instead of 4 h and the observation period only 72 h instead of 14d.
Executive summary:

In a skin irritation study (1984) acc. Journal officiel skin irritation test with 6 New Zealand White rabbits and an exposure time of 24 h (occlusive) methacrylic anhydride was irritating to skin. Observation time was too short for a clear statement of reversability. (Only 72 h instead of 14 h). Therefore methacrylic anhydride has to be classified acc. OECD GHS criteria as follows: Skin irritating Category 2

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.