1-dodecyl-1H-imidazole

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 March 2009 to 22 April 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted in compliance with OECD GLP (1997) and OECD Guideline 429 (2002).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

MTDID 13999

IUPAC Name:

MTDID 13999

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): MTDID 13999
- Substance type: Pure active substance
- Physical state: Liquid
- Analytical purity: 100%
- Purity test date: 09 February 2009
- Lot/batch No.: Batch 338724
- Expiration date of the lot/batch: 27 August 2011

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Postbus 6174, NL-5960 AD Hortst/The Netherlands
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 17.8-21.7
- Housing: Group housed
- Diet (e.g. ad libitum): Pelleted standard diet (Harlan Laboratories GmbH, D-33178 Borchen) ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 24 March 2009 To: 22 April 2009

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0 (control), 1, 2.5, and 5.0 % test substance in vehicle

No. of animals per dose:

5

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: The exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than that recorded in control mice as indicated by the simulation index. The data are compatible with a conventional dose response, although allowance must be made for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION: Each test group of mice was treated by epidermal application to the dorsal surface of each ear lobe (left and right) with 25 uL of the appropriate test item concentration.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The positive control results were as expected, indicating the test method was valid.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Simulation Index relative to the mean of the control group: 1%: 2.9-5.7 2.5%: 9.7-14.7 5.0%: 12.8-17.7

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Control: 461-1172 1%: 2162-4291 2.5%: 7308-10996 5.0%: 9568-12187

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Category 1A Skin Sensitizer Criteria used for interpretation of results: EU

Conclusions:

 Based on the results of this study and CLP classification criteria, the test article is Category 1A skin sensitizer.

Executive summary:

 The dermal sensitizing potential of the test article (colorless liquid, purity 100% CASRN 4303-67-7, batch 338724) was evaluated in a local lymph node assay (LLNA) in female CBA mice. This study was performed in compliance with the Chemicals Act of Germany (2002) and OECD GLP (1997). The study design was based on OECD Guideline 429 (2002). The test article was diluted in vehicle (Acetone/Olive Oil at 4:1 (v/v)) for the appropriate concentrations. A pre-test evaluated 10 and 25% test article on the ear of one mouse mice each for three consecutive days. Treatment with 25% or 10% led to the deaths of both mice after 3 days (25% test article) and 7 days (10% test article). Unintended ingestion following grooming was considered a possible source of the mortality given the known rat acute oral LD50 (641 mg/kg).  A second pre-test evaluated 2.5 and 5% test article for three consecutive days on one mouse each. The animals in the second pre-test did not show signs of irritation or systemic toxicity. Groups of animals (5/treatment) received vehicle, 1, 2.5 or 5% test article on three consecutive days by application on the ears. Three days after the last exposure all animals were subjected to a 3H-methyl thymidine treatment and the auricular lymph nodes were removed to measure the amount of proliferative DNA by disintegrations per minute (DPM). The stimulation index (SI) was calculated for each group and, if possible, the concentration at which the test article could elicit an SI greater than or equal to 3 was determined (EC3). Hexylcinnamic aldehyde (HCA) is tested in this study design every 6 months at the test facility as a positive control and the most recent results indicated that model was valid. Mean DPM/animal values were 1622.5, 4533.7, and 5609.6 for the 1, 2.5 and 5% test article groups, respectively. The mean DPM/animal value for the vehicle control group was 374.9. The SI values for the 1, 2.5 and 5% test article groups were 4.33, 12.09, and 14.96, respectively. The EC3 could not be calculated because all SI were > 3. However, the EC3 is clearly less than 2%, because 1% CASRN 4303-67-7 produced an SI value of 4.33 . Based on the results of this study, the test article is a dermal sensitizer.