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Toxicological information

Skin sensitisation

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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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-dihydroxypropyl methacrylate
EC Number:
227-642-6
EC Name:
2,3-dihydroxypropyl methacrylate
Cas Number:
5919-74-4
Molecular formula:
C7H12O4
IUPAC Name:
2,3-dihydroxypropyl 2-methylprop-2-enoate

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS B.V. Inc., Postbus 6174, 5960 AD Horst,The Netherlands
- Age at study initiation: 9 - 10 weeks (pretest and main test)
- Weight at study initiation: 18.5 - 22.2 g (main test); 18.4 - 21.2 g (pretest)
- Housing: 1 animal per cage
- Diet: Kliba mouse/rat maintenance diet “GLP”, supplied by Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum.
- Water: Drinking water ad libitum
- Acclimation period: al least 5 days before the first application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:
methyl ethyl ketone
Concentration:
25, 50 and 100%
No. of animals per dose:
5
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Mean values and standard deviations of the measured parameters were calculated for the test and control groups from the individual values. The stimulation indices of 3H-thymidine incorporation, cell count, lymph node weight and ear weight were calculated as the ratio of the test group mean values for these parameters divided by those of the vehicle control group or untreated control group.
3H-thymidine incorporation, cell count, lymph node weight and ear weight: WILCOXON-Test

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
0.72
Test group / Remarks:
25% in MEK
Parameter:
SI
Value:
0.8
Test group / Remarks:
50% in MEK
Parameter:
SI
Value:
3.04
Test group / Remarks:
undilutest test substance
Parameter:
SI
Value:
1
Test group / Remarks:
vehicle MEK
Parameter:
SI
Value:
1
Test group / Remarks:
untreated

Any other information on results incl. tables

Test Group

Treatment

³H-thymidine
incorporation
Stimulation Index

Cell Count
Stimulation Index

Lymph Node Weight
Stimulation Index

Ear Weight
Stimulation Index

1

Untreated

1.00

 

1.00

 

1.00

 

1.00

 

2

vehicle MEK

1.00

1.00

 

1.00

1.00

 

3

25% in MEK1

0.72

N.S.

0.78

N.S.

0.86

N.S.

0.98

N.S.

4

50% in MEK1

0.80

N.S.

0.68

N.S.

0.78

N.S.

0.92

N.S.

5

Undiluted test substance2

3.04

#

1.05

N.S.

0.99

N.S.

0.98

N.S.

The statistical evaluations were performed using the WILCOXON-test (# for p0.05, ## for p0.01); N.S. = not significant

 1test group versus vehicle control;2test group versus untreated control

The mean body weight of test group 5 decreased considerably over the study period, indicating systemic toxicity. Beside the body weight loss of test group 5, no further signs of systemic toxicity were noticed during general observation. 

When applied undiluted, the test substance induced a statistically significant increase of 3H-thymidine incorporation into the cells from the auricular lymph nodes at the border of biological relevance (increase to 3.0 fold of control value = stimulation index (SI) ≥ 3.0).However, neither the cell count index nor lymph node weight index substantiate this finding.

No increases in 3H-thymidine incorporation, lymph node cell counts and lymph node weights were observed at the concentrations of 50% and 25%.

No increase of ear weights compared to the respective control group was observed in all concentrations. The animals treated with the undiluted test substance or with the 50% concentration exhibited a slight swelling of the ear skin on study day 1 and 2. Furthermore, an accumulation of the applied test item with concomitant slight erythema of the affected skin in the shoulder and neck region was observed in both concentrations during the observation period. However, the test substance did not induce relevant skin irritation at the application site up to the highest tested concentration. Due to the borderline increase of 3H-thymidine incorporation and the absence of a concentration-dependent effect in combination with the presence of test-substance related body weight loss, the SI-increase in 3H-thymidine incorporation of the undiluted test substance is not considered to indicate a skin sensitizing potential.  

Moreover, due to signs of systemic toxicity, effects observed after application of the undiluted test substance should be considered with cautiousness as induction of rather unspecific systemic effects due to general toxicity cannot be excluded.

Thus, it is concluded that Glycerol Monomethacrylate (GMMA) does not exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.

 

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.
Conclusions:
Glycerol Monomethacrylate (GMMA) does not exhibit a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.