Methacrylic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Principles of method if other than guideline:

other: modified Buehler-test (1965)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The test has been performend bevor LLNA method was estblished

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic acid

EC Number:

201-204-4

EC Name:

Methacrylic acid

Cas Number:

79-41-4

Molecular formula:

C4H6O2

IUPAC Name:

methacrylic acid

Test material form:

liquid

Specific details on test material used for the study:

purity: 98.5 % (0.001% max hydroquinone CAS 123-31-9; 0.027 max MEHQ, CAS 150-76-5)
Haskell number 19762
Clear liquid
Lot 5-031342

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

Body weight 336-428 grams obtained from Davidson Mill Farm, Jamesburg, NJ. Animals individually identified by color coding.
Temperature: l8.8°C - 22.1°C
Relative Humidity: 56 - 80 %
Light: 12 hour light'dark cycle
Diet: Guinea Pig Formula and tap water were provided ad libitum.
Caging: Stainless steel with elevated wire mesh flooring, one guinea pig/cage.

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

0.4 ml; the first induction application was a 20% dilution in water ; the second and third induction applications was 15% in water.

Day(s)/duration:

6 hrs

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

Route:

epicutaneous, occlusive

Vehicle:

water

Concentration / amount:

The challenge application was 10% in water.

Day(s)/duration:

6 hrs

No. of animals per dose:

20: test substance
10: vehicle control
5: positive control
5: naive positive control

Details on study design:

RANGE FINDING TESTS:
Five groups of four naive animals each were exposed to two different concentrations of methacrylic acid where both sides of each group of animals were closely clipped and treated with 0.4 ml as 75% v/v, 60% v/v, 45% v/v, 30% v/v, 25% v/v, 20% v/v, 10% v/v, 5% v/v and/or 1 % v/v dilutions in deionized water
Based on the irritation results, the first induction application was applied as a 20% v/v dilution in deionized water. The concentration was reduced to 15% v/v the second - and third induction applications because of the severity of reactions from the first induction application.
A 10% v/v dilution in deionized water was applied as the challenge application.

MAIN STUDY

A. INDUCTION EXPOSURE
- Exposure: Once a week for three weeks, for a total of three, six-hour applications with the test article. - Test groups: 20 animals
- Site: left flank
- - Concentrations: first induction: A portion of 0.4 ml of 20 % methacrylic acid in deion. Water ,
second and third induction: A portion of 0.4 ml of 15 % methacrylic acid in deion. Water ,
- Evaluation of dermal Irritation at 24, 48 and 72 hours from the initial patch application.
Scoring for irritation at 24, 48 and 72 hours from initial patch application.

- Vehicle control: Control group: (10 animals ) deionized water only
- Positive control: (5 animals) 0.4 ml portion of 0.1 % 1-chloro-2,4-dinitrobenzene (DNCB) w/v in 50%
ethanol: 0.9% saline

- The test article was applied to a gauze patch (1 x 1 inch) which had been placed onto a piece of plastic film. After positioning the patch onto the prepared skin tes1. site, the plastic material was wrapped snugly around the trunk of the animal and secured with elastic tape.
B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: 14 days after third application
- Exposure period: 6 hrs
- Test groups: Test article group
- Control group: vehicle control, positive control, naive positive control
- Site: right flank
- Concentrations: 10% v/v dilution in deionized water
- Evaluation (hr after challenge): 24, 48 and 72 hrs

Challenge controls:

vehicle group, positive control group and naive positive control group ( treated with DNCB at challenge)

Positive control substance(s):

yes

Remarks:

99+% DNCB

Results and discussion

Positive control results:

The positive control (DCNB) induced and challenged as an 0.1% w/v concentration in a 50% ethanol: 0.9% saline solution is a skin sensitizer in albino guinea pigs. After challenge application of the positive control article, no dermal irritation was observed for the naive postive control animals.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10% in deionized water challenge concentration

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Results 2

Hours after challenge:

72

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Results 3

Hours after challenge:

72

Group:

negative control

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Test article group: no dermal irritation to eschar was observed during the induction phase of the study. After the challenge application no redness was observed other than slight patchy redness exhibited at 48 hrs by 2/20 animals. The incidence of sensitization was 0/20 and the severity was 0.0, 0.5 and 0.0 for 24, 48 and 72 hours, respectively.

Vehicle control group:

No dermal irritation to eschar was observed during the induction phase of the study. After the challenge application no redness was observed other than slight patchy redness exhibited at 48 hrs by 2/10 animals, and 3/10 animals at 72 hours. The vehicle site did not exhibit any redness.

Positive control group (1-chloro-2,4-dinitrobenzene): After the challenge application, moderate redness was observed in 5/5 animals at 24 hours. The incidence of sensitization was 5/5 and severity was 2.0 at 24 hours, 1.1 at 48 hours and 1.0 at 72 hours.

Naive positive control group: After the challenge application of the positive control article, no dermal irritation was observed for any of the anirnals.

Tables see under attached full study report

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a valid guideline study, MAA was not a dermal sensitizer in albino guinea pigs. Methacrylic Acid did appear to be a skin irritant at concentrations of 15% and above.

Executive summary:

Methacrylic acid was tested in a Modified Bühler test (version 1981) in 20 male Guinea pigs. Based on the results of a range finding test and observations during the main test first induction was performed with 0.4 ml 20 % methacrylic acid in deionized water. Second and third experiment has been performed due to skin reactions in the first experiment at concentrations of 15 % MAA in deionized water. Challenge has been performed 14 days after third induction with 10 % methacrylic acid in deionized water.

Methacrylic acid is not a dermal sensitizer in albino guinea pigs.

The positive control, 1-chloro-2,4-dinitrobenzene, when induced and challenged as an 0.1 % w/v concentration in a 50% ethanol: 0.9% saline solution is a skin sensitizer in albino guinea pigs.