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Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 August - 12 September 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 429) and in compliane with GLP.

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 (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Reference substance name:
IN 78281
IUPAC Name:
IN 78281
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): IN 78281
- Physical state: White powder
- Analytical purity: 100.1 %
- Lot/batch No.: 7889-058-10
- Supplier: Boehringer Ingelheim Pharmaceuticals
- Expiration date of the lot/batch: Dec 2006
- Stability under test conditions: Stability data on bulk test material was not provided by the Sponsor
- Storage condition of test material: Room temperature

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: 19 to 24 grams
- Housing: housed in groups of 5 per cage
- Diet (e.g. ad libitum): ad libitum, Certified Rodient Diet 7012C
- Water (e.g. ad libitum): ad libitum, tab water
- Acclimation period: animals were acclimated 8 days prior to their first dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.2. to 27.8 °C
- Humidity (%): 30 to 48 %
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark

Study design: in vivo (non-LLNA)

Positive control substance(s):
yes

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
5, 15 or 35 %
No. of animals per dose:
25 total; 5 per concentration; 5 per positive and negative control, respectively
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: 35 % (w/v)
- Irritation: up to the solubility limit not irritating

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: Increases in 3H-thymidine incorporation relative to the vehicle-treated control were derived for each group and recorded as stimulation index (SI). The criterion for a positive response is that one or more concentrations of a test article elicits a 3-fold or greater increase in isotope incorporation relative to the vehicle control as indicated by the SI.

TREATMENT PREPARATION AND ADMINISTRATION: Mice were treated on the dorsal surface of both ears, once per day on Days 1, 2 and 3. Approximately 24 +- 2hours separated each application of test article. On Day 6, the mice were injected i. v. with 20 µCi of 3H-thymidine in 250 µl of sterile saline.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
The mean disintegrations per minute (DPM) for each group was evaluated using SYSTAT version 9.01, developed by SPSS, Inc. Individual DPM values were analyzed by log transformation (base 10) of the data. The evaluation of the equality of means for the DPM and body weight data were made by a one-way analysis of variance using the F distribution to assess statistical significance. If statistically significant differences between the means were found, a Dunnett's test was used to determine the degree of significance from the control means.

Results and discussion

Positive control results:
The positive control resulted in very slight erythema on days 3 through 6 and very slight edema on days 4 through 5. Also the ears of the positive control mice appeared wet on days 2 through 5.

Any other information on results incl. tables

 Group  Treatment  Dose  DPM (mean+-sem)  SI  Result
 1  DMF  -  413 +- 56  -  negative
 2  IN 78281  5 %  368 +- 34  0.89  negative
 3  IN 78281  15 %  480 +- 80  1.16  negative
 4  IN 78281  35 %  425 +- 66  1.03  negative
 5  HCA  35 %  3442 +- 410  8.33  positive

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Although concentrations of dosing formulations were not confirmed, treatment with IN00078281 at concentrations up to 35% did not result in an SI of 3 or greater. Therefore, based on the data from this study, IN00078281 is not considered to have skin sensitizing potential.