Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Equivalent to Guideline strudy

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
2006
Reference Type:
publication
Title:
Unnamed
Year:
2011

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
As described in: Kimber I, Basketter D A. The murine local lymph node assay: a commentary on collaborative studies and new directions. Food Chem Toxicol 1992: 30: 165–169.
GLP compliance:
not specified
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl methacrylate
EC Number:
201-297-1
EC Name:
Methyl methacrylate
Cas Number:
80-62-6
Molecular formula:
C5H8O2
IUPAC Name:
methyl methacrylate
Test material form:
liquid
Specific details on test material used for the study:
MMA (99.96% pure) was supplied by Lucite International UK Ltd via Cassel Works, Cleveland, UK.

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
- Young adult CBA/Ca mice (Harlan, Bicester, Oxfordshire, UK)
- Age: 8–12 weeks
- Housing: metal cages
- Food: SDS PCD pelleted diet; Special Diets Services Ltd, Witham, UK)
- Water: ad libitum.
-Temperature: 22 +/- 3°C
- Relative humidity: 50 +/-20%
- Lightning: 12 hr light/dark cycle.

Study design: in vivo (LLNA)

Vehicle:
other: acetone or acetone/olive oil (4:1 v/v)
Concentration:
0, 10, 30, 50 75, and 100% (neat)
No. of animals per dose:
4 per group
Details on study design:
Groups of mice were exposed topically on the dorsum of both ears to 25 µl of various concentrations of chemical, or to the same volume of vehicle alone, daily for 3 consecutive days. Five days after the initiation of exposure, all mice were injected intravenously via the tail vein with 20 µCi of [3H] methyl thymidine in 250 µl of phosphate buffered saline. Five hrs later, mice were killed and the draining auricular lymph nodes were excised and pooled for each experimental group. A single-cell suspension of lymph node cells (LNC) was prepared; approximately 12 hr later, incorporation of [3H]TdR was measured and a stimulation index relative to the concurrent vehicle-treated control value was derived.
Positive control substance(s):
other: 2,4-Dinitrochlorobenzene
Statistics:
The estimated concentration of chemical required inducing an SI of 3 relative to concurrent vehicle treated controls, or EC3 value, was derived by linear interpolation of dose–response data.
The EC3 value was calculated by interpolating between 2 points on the SI axis, one immediately above, and the other immediately below, the SI value of 3.

Results and discussion

Positive control results:
Positive control: 2,4-Dinitrochlorobenzene (DNCB), Vehicle: Acetone/Olive Oil):
Conc (% w/v) SI
0 1
0.01 1.4
0.025 2.2
0.05 4.0
0.1 9.8
0.25 16.2

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
1.4
Test group / Remarks:
10 % (w/v)
Remarks on result:
other: Vehicle: acetone
Parameter:
SI
Value:
2.3
Test group / Remarks:
30 % (w/v)
Remarks on result:
other: Vehicle: acetone
Parameter:
SI
Value:
2
Test group / Remarks:
50 % (w/v)
Remarks on result:
other: Vehicle: acetone
Key result
Parameter:
SI
Value:
4.4
Test group / Remarks:
75 % (w/v)
Remarks on result:
other: Vehicle: acetone
Key result
Parameter:
SI
Value:
7.3
Test group / Remarks:
100 % (w/v)
Remarks on result:
other: Vehicle: acetone
Parameter:
SI
Value:
1.5
Test group / Remarks:
10 % (w/v)
Remarks on result:
other: Vehicle: acetone/olive oil
Parameter:
SI
Value:
1.5
Test group / Remarks:
30 % (w/v)
Remarks on result:
other: Vehicle: acetone/olive oil
Parameter:
SI
Value:
1.5
Test group / Remarks:
50 % (w/v)
Remarks on result:
other: Vehicle: acetone/olive oil
Key result
Parameter:
SI
Value:
4.4
Test group / Remarks:
75 % (w/v)
Remarks on result:
other: Vehicle: acetone/olive oil
Key result
Parameter:
SI
Value:
3.6
Test group / Remarks:
100 % (w/v)
Remarks on result:
other: Vehicle: acetone/olive oil
Key result
Parameter:
EC3
Value:
ca. 60
Test group / Remarks:
Vehicle: acetone
Key result
Parameter:
EC3
Value:
ca. 90
Test group / Remarks:
Vehicle: acetone/olive oil
Cellular proliferation data / Observations:
see table below

Any other information on results incl. tables

Desintegrations per minute (dpm)
Conc. (% w/v) MMA, vehicle acetone MMA, vehicle acetone/olive oil DNCB/ pos. Ctrl., vehicle acetone/olive oil
0 137 243 609
0.01 ND ND 839
0.025 ND ND 1352
0.05 ND ND 2455
0.1 ND ND 5971
0.25 ND ND 9843
10 205 341 ND
30 312 363 ND
50 274 369 ND
75 605 513 ND
100 (neat) 999 874 ND
Stimulation Index (SI)
Conc. (% w/v) MMA, vehicle acetone MMA, vehicle acetone/olive oil DNCB/ pos. Ctrl., vehicle acetone/olive oil
0 1.0 1.0 1.0
0.01 ND ND 1.4
0.025 ND ND 2.2
0.05 ND ND 4.0
0.1 ND ND 9.8
0.25 ND ND 16.2
10 1.5 1.4 ND
30 2.3 1.5 ND
50 2.0 1.5 ND
75 4.4 2.1 ND
100 (neat) 7.3 3.6 ND

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
In this local lymphnode assay methyl methacrylate attained the criteria of Skin sens Category 1 B
Executive summary:

In an mouse local lymphnode assay (Betts 2006) methyl methacrylate was tested at concentrations of 10; 30; 50; 75 and 100 % in two different vehicles (acetone and acetone/olive oil). EC50 values were 50 % (acetone) and 90 % (acetone/olive oil). In this study methyl methacrylate is a weak skin sensitizer and attained in this study the criteria of skin sens category 1 B.