1H-Indole-6-carboxylic acid, 3-cyclopentyl-1-methyl-, 1-methylethyl ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

propan-2-yl 3-cyclopentyl-1-methyl-1H-indole-6-carboxylate

EC Number:

935-121-6

Cas Number:

1253789-90-0

Molecular formula:

C18 H23 N O2

IUPAC Name:

propan-2-yl 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): CD00006066XX
- Physical state: yellow powder
- Storage condition of test material: room temperature
- Lot/batch No.: 7330-038-2
- Expiration date of the lot/batch: 28 February 2007
-Purity : 98.0 %

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 - 12 weeks
- Weight at study initiation: 20 - 27 g
- Housing: Animals were group housed ( 5 per cage ).
- Diet (e.g. ad libitum): All 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 (10 %, 5 %, 2.5 %, ) of the test article

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 10 % (w/v). Therefore, the dose levels selected for the assay were 2.5, 5.0 and 10 % (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 8.17.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Concentration 2.5 % SI = 1.52 Concentration 5.0 % SI = 4.38 Concentration 10 % SI = 4.47

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Concentration 2.5 % DPM ~ 504 Concentration 5.0 % DPM ~ 1451 Concentration 10 % DPM ~ 1480

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

Migrated information

Conclusions:

A Test material is considered to have skin senitizing 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 positive response.
Although the dosing solution concentration were nor verified, treatment with CD00006066XX at nominal concentrations of 5% and 10% resulted in
an SI of 3 or greater.Therefore, based on the data from this study, CD00006066XX , is considered to have skin sensitizing potential with an EC3 of
3.79.

Executive summary:

Objective

The purpose of this study was to determine if CD00006066XX 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 CD00006066XX at 2.5, 5 and 10 % 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 CD00006066XX. The positive control, HCA, resulted in very slight erythema on Day 3 through 4. Also the ears appeared wet on days 2 through 5 in all the HCA treated animals. The ears also appeared wet on day 4 in all the mice treated with test article at 2.5%, in 4 of 5 mice treated with 5% and 1 of 5 mice treated with 10%. There were no other findings.

At termination, the lymph node from the mice treated with CD00006066XX and AOO were normal in size and appearance except for one of five animals treated with the test article at 5%. The lymph nodes from this mouse as well as all the mice in the HCA group were enlarged but were otherwise normal in appearance.

The positive control resulted in a stimulation index of 8.17.

Exposure to CD00006066XX at 2.5, 5 and 10 % (w/v) resulted in stimulation indices of 1.52, 4.38 and 4.47, respectively. Statistically significant differences were also observed for the mean log DPM of the group treated with 5 % and 10 % CD00006066XX when compared to the vehicle group. The EC3 was calculated to be 3 .79.

Conclusion

A Test material is considered to have skin senitizing 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 positive response.

Although the dosing solution concentration were not verified, treatment with CD00006066XX at nominal concentrations of 5 and 10 % resulted in an SI of 3 or greater. Therefore, based on the data from this study, CD00006066XX , is considered to have skin sensitizing potential with an EC3 of 3.79.