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Description of key information

The test substance shows a skin sensitizing potential in the Murine Local Lymph Node Assay.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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
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)
Species:
mouse
Strain:
CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS GmbH, NL-5800 AN Venray
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 17.7 g – 18.7 g (pretest); 17.0 g – 21.8 g (main test)
- Housing: single housing (Polycarbonate cages type MII with mesh wire tops)
- Diet (e.g. ad libitum): Mouse and rat maintenance diet “GLP”, Granovit AG, Kaiseraugst, Switzerland; ad libitum
- Water (e.g. ad libitum): drinking water; ad libitum
- Acclimation period: at least 5 days before the first application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%): 45 – 65%
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
methyl ethyl ketone
Concentration:
1, 5 and 10%
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 per test group from the individual values. The stimulation indices of 3H-thymidine incorporation, cell count, lymph node weight and ear weight measurements were calculated by dividing the mean values and/or single animal values of the test substance treated groups by the mean of the vehicle treated group.
3H-thymidine incorporation, cell count, lymph node weight and ear weight (WILCOXON-Test)
Parameter:
EC3
Remarks:
%
Value:
6.2
Parameter:
other: EC1.5 %
Value:
5.3

Test Group

Treatment

3H-thymidine incorporation Stimulattion Index1

Cell Count Stimulation Index1

Lymph Node Weight Stimulatin Index1

Ear Weight Stimulation Index1

1

Vehicle MEK

1.00

1.00

1.00

1.00

2

1% in MEK

1.40

1.17

1.01

0.97

3

5% in MEK

       2.17  ##

     1.44 ##

   1.19 #

0.96

4

10% in MEK

       5.76  ##

     2.40 ##

     1.82 ##

0.99

 1versus mean of test group 1 (vehicle control)

The statistical evaluations were performed using the WILCOXON-test ( # for p0.05, ##for p0.01)

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
Thus, it is concluded that Laromer IPGA exhibits a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.
The threshold concentration for sensitization induction was >5% <10%. The EC 3 (estimated concentration that leads to the SI of 3.0) for 3H-thymidine incorporation and the EC 1.5 (estimated concentration that leads to the SI of 1.5) for cell count was calculated by linear regression from the results of these concentrations to be 6.2% and 5.3%, respectively.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

The skin sensitizing potential of Laromer IPGA was assessed using the radioactive Murine Local Lymph Node Assay. The assay simulates the induction phase for skin sensitization in mice. It determines the response of cells in the auricular lymph nodes to repeated application of the test substance to the dorsal skin of the ears. Groups of 5 female CBA/CaOlaHsd mice each were treated with 1%, 5% and 10% (w/w) preparations of the test substance in MEK or with the vehicle alone. Each test animal was treated with 25 μL per ear of the appropriate test-substance preparation or the vehicle alone, applied to the dorsal surfaces of both ears on three consecutive days. Three days after the last application, 20 μCi 3H-thymidine in 250 μL sterile saline were injected into the tail vein of the mice. About 5 hours after the 3H-thymidine injection, the mice were sacrificed and the auricular lymph nodes were removed. No signs of systemic toxicity were noticed in all animals during general observation. The test-substance concentrations did not cause increases (SI ≥ 1.25) in ear weights demonstrating the absence of relevant ear skin irritation. The threshold concentration for sensitization induction was >5% <10%. The EC 3 (estimated concentration that leads to the SI of 3.0) for 3H-thymidine incorporation and the EC 1.5 (estimated concentration that leads to the SI of 1.5) for cell count was calculated by linear regression from the results of these concentrations to be 6.2% and 5.3%, respectively. Thus, it is concluded that Laromer IPGA exhibits a skin sensitizing potential in the Murine Local Lymph Node Assay under the test conditions chosen.

Justification for classification or non-classification

Based on the results of the skin sensitization testing, the test item is classified as skin sensitization cat. 1B (H317) according to Regulation (EC) No 1272/2008 (CLP).