Methacrylic acid, monoester with propane-1,2-diol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Data source

Reference

Reference 1

Reference Type:

publication

Title:

The local lymph node assay: Developments and applications

Author:

Kimber I., Dearman R.J., Scholes E.W., Basketter D.A.

Year:

1994

Bibliographic source:

Toxicology 93(1): 13 - 31

Reference 2

Reference Type:

publication

Title:

Comparison of the local lymph node assay with the guinea-pig maximization test for the determination of a range of contact allergens

Author:

Basketter DA, Scholes EW (1992) .

Year:

1992

Bibliographic source:

Fd. Chem. Toxic. 30: 65-69

Reference 3

Reference Type:

publication

Title:

The Local Lymph Node Assay: Results of a Final Inter-laboratory Validation under Field Conditions

Author:

Scholes, E.W., et al

Year:

1992

Bibliographic source:

JOURNAL OF APPLIED TOXICOLOGY, VOL. 12(3), 217-222

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Principles of method if other than guideline:

Modified by Kimber, I., et al (1989, 1991a, 1991b)

GLP compliance:

no

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Methacrylic acid, monoester with propane-1,2-diol

EC Number:

248-666-3

EC Name:

Methacrylic acid, monoester with propane-1,2-diol

Cas Number:

27813-02-1

Molecular formula:

C7H12O3

IUPAC Name:

1-hydroxypropan-2-yl 2-methylprop-2-enoate; 2-hydroxypropyl 2-methylprop-2-enoate

Test material form:

liquid

Details on test material:

The chemical 2-propenoic acid, 2-methyl-, monoester with 1,2-propanediol (CAS No. 27813-02-1) consists of two isomers. This occurs due to the method of industrial production, which is usually either the reaction between methacrylic acid and propylene oxide, or methacrylic acid esterification of 1,2-propanediol. The predominant isomer is the secondary alcohol 2-propenoic acid, 2-methyl, 2-hydroxypropyl ester, which is assigned the CAS No. 923-26-2, and the isomer 2-propenoic acid, 2-methyl, 2-hydroxy- 1-methylethyl ester, the other chemical in this group, for which CAS 4664-49-7 is assigned. The purification of the two isomers requires extensive effort and it is supposed no such effort has been taken during data collection otherwise noted. Therefore toxicity information for both CAS No. 923-26-2 and CAS No. 27813-02-1 is considered to be applicable to both chemicals..

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon or Barriered Animal Breeding Unit, Alderley Park
- Age at study initiation: young adult, 8-12 weeks

Study design: in vivo (LLNA)

Vehicle:

other: Acetone olive oil or DMF

Concentration:

5.0, 10.0, 25.0, 50.0%

No. of animals per dose:

4

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: murine local lymph node assay
- Criteria used to consider a positive response: LLNA results are expressed as testlcontrol (TIC) ratios, where ratios equal to or greater than three indicate a positive proliferative response.

TREATMENT PREPARATION AND ADMINISTRATION: 25 uI of one of three concentrations of the test chemical on the dorsum of both ears daily for three consecutive days.

Positive control substance(s):

mercaptobenzothiazole (CAS No 149-30-4)

other:

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

0.9

Test group / Remarks:

50%

Remarks on result:

other: in the paper the SI values were expressed as T/C values were values < 3 indicate a positive result

Results 2

Parameter:

SI

Value:

1

Test group / Remarks:

25%

Remarks on result:

other: in the paper the SI values were expressed as T/C values were values < 3 indicate a positive result

Results 3

Parameter:

SI

Value:

0.8

Test group / Remarks:

10%

Remarks on result:

other: in the paper the SI values were expressed as T/C values were values < 3 indicate a positive result

Results 4

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Concentration (%) Laboratory A (vehicle) Laboratory B (vehicle) Laboratory C (vehicle) Laboratory D (vehicle) 5 1.1 (AOO) - (AOO) - (AOO) - (DMF) 10 1.2 0.8 1.0 1.4 25 1.3 1.0 1.9 0.7 50 - 0.9 0.8 0.9

Any other information on results incl. tables

To document the consistency in results of collaborating laboratories, the local lymph node assay was conducted under field conditions by four laboratories.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Conclusions:

The test substance is considered to be non-sensitizing following conduct of the local lymph node assay.

Executive summary:

The sensitization potential of Hydroxypropyl methacrylate was tested in a local lymph node assay using a modified protocol. This inter-laboratory study used four laboratoires to demonstrate the consistency of results. Groups of mice received 25 uL of one of

four concentrations of the test chemical on the dorsum of both ears daily for three consecutive days. Control mice received an equal volume of the relevant vehicle alone. The proliferative activity lymph node cells (LNC) was expressed as the number of radioactive disintegrations per minute (dpm) per lymph node for each experimental group. The ratio of 3HTdR incorporation by LNC of test

lymph nodes relative to that recorded for control lymph nodes test/control (T/C) ratio was calculated for each test group. HPMA was considered not to be a sensitizer as the T/C ratio was not greater than 3.