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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)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
propan-2-yl 2-bromo-3-cyclopentyl-1-methyl-1H-indole-6-carboxylate
EC Number:
936-073-9
Cas Number:
1253791-42-2
Molecular formula:
C18 H22 Br N O2
IUPAC Name:
propan-2-yl 2-bromo-3-cyclopentyl-1-methyl-1H-indole-6-carboxylate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): CD00006062XX
- Physical state: white powder:
- Storage condition of test material: room temperature
- Lot/batch No.: BIC 11008957
- Expiration date of the lot/batch: 31 March 2007
- Composition / Purity : Purity was 101.7 %

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Jackson Laboratories, Bar Harbor, ME 04609
- Age at study initiation: 10 weeks
- Weight at study initiation: 20 - 24 g
- Housing: Animals were group housed ( 5 per cage ).
- Diet (e.g. ad libitum): Animals had access to Certified Rodent Diet 7012C ad libitum.
- Water (e.g. ad libitum): Tap water was available ad libitum, via water bottles.
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.3 - 27.2
- Humidity (%): 28 - 54
- Photoperiod (hrs dark / hrs light): 12 : 12

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
Three consecutive concentrations (2.5 %,1.0 %;0.5 % )
No. of animals per dose:
5 animals per dose
Details on study design:
Solubility Test : Based on the solubility test, acetone/ olive oil was selected as the vehicle and the highest concentration of the test article that
could be achieved was 2.5 % (w/v). Therefore, the dose levels selected for the assay were 0.5, 1.0 and 2.5 % (w/v).


Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The positive control, 35 % (v/v) HCA, resulted in a stimulation index (SI) of 9.42.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Concentration 0.5 % SI = 1.02 Concentration 1.0 % SI = 0.91 Concentration 2.5 % SI = 1.49
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Concentration 0.5 % DPM ~ 345 Concentration 1.0 % DPM ~ 306 Concentration 2.5 % DPM ~ 501

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
A test material is considered to have skin sensitizing activity if, at one or more concentrations, it induces a 3-fold or greater increase in proliferative
activity relative to the concurrent vehicle treated control group. Thus, a stimulation index (SI) of 3.0 or greater is regarded as a positive response.
Although the dosing solution concentration were not verified, treatment with CD00006062XX at nominal concentrations up to 2.5 % did not result in an SI of 3 or greater.
Therefore, based on the data from this study, CD00006062XX is not considered to have skin sensitizing potential.
Executive summary:

Objective

The purpose of this study was to determine if CD00006062XX would induce a hypersensitivity response in mice as measured by the proliferation of lymphocytes in the draining nodes.

Methods

Five groups of CBA/J female mice were treated on the dorsal surface of both ears once per day for 3 days with CD00006062XX at 0.5, 1.0 and 2.5 % with the vehicle (acetone/olive oil (AOO)), or with the positive control ( 35 % Hexylcinnamaldehyd(HCA)) . On day 6, the mice were injected , i.v., with 20µCi of ³H-thymidine in sterile saline. Five hours later, the mice were euthanized and the draining auricular lymph nodes were removed. The lymph node cells were percipitated with 5 % trichloroacetic acid (TCA) and the pellets counted in a ß-scintillation counter to determine incorporation of the ³H-thymidine .

Results

No erythema or edema was noted in any of the groups treated with AOO or CD00006062XX. The positive control, HCA, resulted in very slight erythema on Day 3 through 5. Also the ears of the mice treated with the positive control appeared wet on day 2 through day 5. There were no other findings.

At termination, the lymph node from the mice treated with CD00006062XX and AOO were slightly enlarged in size but normal in appearance. The lymph node from the mice in the HCA group were enlarged but were otherwise normal in appearance.

The positive control resulted in a stimulation index of 9.2.

Exposure to CD00006062XX at 0.5, 1 and 2.5 % (w/v) resulted in stimulation indices of 1.02, 0.91 and 1.49, respectively. There were no statistically significant differences found when the mean log DPM for any of the test article treatment groups was compared to the vehicle group.

Conclusion

A test material is considered to have skin sensitizing activity if, at one or more concentrations, it induces a 3-fold or greater increase in proliferative activity relative to the concurrent vehicle treated control group. Thus, a stimulation index (SI) of 3.0 or greater is regarded as a positive response. Although the dosing solution concentration were nor verified, treatment with CD00006062XX at nominal concentrations up to 2.5 % did not result in an SI of 3 or greater. Therefore, based on the data from this study, CD00006062XX is not considered to have skin sensitizing potential.