Methacrylic anhydride

Skin irritation / corrosion

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

Guideline:

other: Journal officiel de la Republique Francaise, 21 February 1982

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic anhydride

EC Number:

212-084-8

EC Name:

Methacrylic anhydride

Cas Number:

760-93-0

Molecular formula:

C8H10O3

IUPAC Name:

2-methylprop-2-enoyl 2-methylprop-2-enoate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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

Results 13

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

Results 14

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

Results 15

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

Results 16

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

Results 17

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

Results 18

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

Results 19

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

Results 20

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

Results 21

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

Results 22

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

Results 23

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

Results 24

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

Results 25

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

Results 26

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

Results 27

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 28

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 29

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 30

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 31

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 32

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 33

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 34

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 35

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 36

Irritation parameter:

edema score

Basis:

animal #4

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 37

Irritation parameter:

edema score

Basis:

animal #5

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

Results 38

Irritation parameter:

edema score

Basis:

animal #6

Time point:

48 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

intact shaved skin, no scoring at 48 h

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

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