Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 February 2007 to 12 March 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted under GLP conditions

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
Radioactive measurements were performed using a Packard scintillation counter type 2800TR instead of type 1900TR. The 2800TR is a validated system. Therefore, the results obtained for radioactive measurements are not affected.
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): MTDID 6675
- Substance type: Clear colourless liquid
- Physical state: Liquid
- Analytical purity: Formulation tested is 30% active ingredient in water.
- Purity test date: 12/20/2005
- Lot/batch no.: 140499-19/10
- Expiration date of the lot/batch: 01 December 2008
- Storage condition of test material: At room temperature in the dark

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA strain, inbred, SPF-Quality
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L'Arbresle Cedex, France
- Age at study initiation: Approx. 10 weeks old
- Weight at study initiation: 21-26 grams
- Housing: Individually housed in labeled Macrolon cages (MI type; height 12.5 cm) containing sterilized sawdust as beding material (Litalabo, S.P.P.S., Argenteuil, France)
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdaten GmbH, Soest, Germany) ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 5 days before the start of treatment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0-23.7 degrees Celsius
- Humidity (%): 36-81%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 21 February 2007To: 12 March 2007

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
No. of animals per dose:
Five females per group
Details on study design:
RANGE FINDING TESTS:
- Irritation: Preliminary irritation study was conducted in order to select highest test substance concentration to be used in the main study. 100% (undiluted) was selected as the hightest concentration.
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: SI value greater than or equal to 3 is considered a sensitiser
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
The six monthly reliability check with Hexylcinnamic aldehyde indicates that the Local Lymph Node Assay as performed at NOTOX is an appropriate model for testing for contact hypersensitivity.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: SI values calculated for the substance concentrations 25, 50, and 100% were 1.8, 2.7, and 4.9 respectively.
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Mean DPM/animal values for the experimental groups treated with the test substance concentration 25, 50, and 100% were 553, 800, and 1460 respectively. The mean DPM/animal value for the vehicle control group was 301.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The SI values calculated for the 25, 50 and 100% concentrations were 1.8, 2.7 and 4.9 respectively. The data showed a dose response and an EC3 value of 56.8% was calculated. Based on these results and according to the recommendations made in the test guidelines, the test substance is regarded as skin sensitizer (GHS Category 1, EC labeling phrase R 43).
Executive summary:

The purpose of this study was to assess the potential of the test substance to cause contact hypersensitivity in mice according to OECD Test Guideline 429. Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, groups of five mice were treated with test substance concentrations of 0, 25, 50 or 100% (corresponding to 0, 7.5, 15 and 29.9% of the main active component) in dimethylformamide on three consecutive days, by open application on the ears. Three days after the last exposure, all animals were injected with 3H-methyl thymidine and after five hours the draining (auricular) lymph nodes were excised. After precipitating the DNA of the lymph node cells, radioactivity measurements were performed. The activity was expressed as the number of disintegrations per minute (dpm) and a stimulation index (SI) was calculated for each test article group. No skin reactions were observed in any of the animals examined. The majority of nodes were considered normal in size, except for the enlarged nodes of four animals treated at 100%. No macroscopic abnormalities of the surrounding area were noted. The SI values calculated for the 25, 50 and 100% concentrations were 1.8, 2.7 and 4.9 respectively. The data showed a dose response and an EC3 value of 56.8% was calculated. Based on these results and according to the recommendations made in the test guidelines, the test substance is regarded as skin sensitizer (GHS Category 1, EC labeling phrase R 43).

Categories Display