Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methylcyclopentane-1,3-dione
EC Number:
212-153-2
EC Name:
2-methylcyclopentane-1,3-dione
Cas Number:
765-69-5
Molecular formula:
C6H8O2
IUPAC Name:
2-methylcyclopentane-1,3-dione
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test item: Methyl-cyclopentanedioneCAS No.: 765-69-5Batch No.: S39129NPhysical state: solid, crystalline powderColour: beigeStorage: at a temperature of 15 to 30 °C

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
Species and strain: CBA/Ca Ola Hsd miceSource: TOXI-COOP ZRT.Hygienic level at arrival: SPFHygienic level during the study: Good conventionalNumber of animals: 24 animals/main test (4 animals/treatment group)Sex: Female, nulliparous, non-pregnantAge of animals: Young adult mice; 10-11 weeks old (at start of the main test)Body weight range at starting: 17.6-22.2 gAcclimatization time: 7 daysAnimal health: Only healthy animals were usedHousing during acclimatization period: Grouped caging in small groupsHousing during the test: Grouped caging (4 animals/cage)Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.Temperature: 22 ± 3 °CRelative humidity: 30 – 70 %

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Remarks:
AOO (acetone:olive oil, 4:1) for positive control groups
Concentration:
The test item was administered at three different concentrations (5; 2,5; 1 w/v%) according to the results of the dose range finding test.
No. of animals per dose:
4 animal/dose
Details on study design:
Selection of test item concentrations was based on the results of a formulation evaluation and also results of preliminary irritation/toxicity test to find an appropriate solvent and the maximum applicable concentration according to the relevant guidelines [1-2]. Based on the preliminary test results the test item was examined in the main test at 5 %, 2.5 % and 1 % (w/v) concentrations as formulations in the selected vehicle of N,N-Dimethylformamide (DMF). Appropriate positive control (α-Hexylcinnamaldehyde [HCA] in 25 % (w/v) concentration), furthermore two negative control groups dosed with the vehicles of the test and positive control groups, respectively, were employed.The positive control item (25 % (w/v) HCA in Acetone: Olive oil 4:1 (v/v) mixture, AOO) induced the appropriate stimulation over the control, thus confirming the validity of the assay.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: see Remark
Remarks:
The stimulation index (SI = the DPN of a treated (positive control or test item) group divided by the DPN of the respective negative control group) for each treatment group was also calculated. A stimulation index of 3 or greater is an indication of a positive result. When monotonic dose-response is seen, attempt is made to calculate EC3 (dose calculated to induce a stimulation index of 3) with the help of linear regression on dose-response relationship. All calculations were made by Microsoft Excel Software. (See Table1 for the values.)
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
DPM (disintegration per minute) was measured for each treatment group. The measured DPM values were corrected with the background DPM value. The average of the two measured DPM values of 5 % (w/v) TCA solutions was used as the background DPM value. The results were expressed as DPN (DPM divided by the number of pooled lymph nodes). (See Table1 for the values.)
Parameter:
SI
Value:
0.5
Remarks on result:
other: Methyl-cyclopentanedione 5 % in DMF
Parameter:
SI
Value:
0.6
Remarks on result:
other: Methy-cyclopentanedione 2.5 % in DMF
Parameter:
SI
Value:
0.5
Remarks on result:
other: Methyl-cyclopentanedione 1 % in DMF

Any other information on results incl. tables

Test Group Name

Measured

DPM/group

Group*

DPM

DPN

(DPM/Node)

Stimulation

Index Values

Vehicle control for the positive control: AOO

7283

7258.0

907.3

1.0

Positive control:
25 % HCA
in AOO

93261

93236.0

11654.5

12.8

Methyl-cyclopentanedione
5 %
in DMF

2857

2832.0

354.0

0.5

Methy-cyclopentanedione
2.5
% in DMF

3069

3044.0

380.5

0.6

Methyl-cyclopentanedione
1 %
in DMF

2956

2931.0

366.4

0.5

Vehicle control for the test item: DMF

5397

5372.0

671.5

1.0

 *Group DPM = measured DPMgroup- average DPMbackground

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
In conclusion, under the conditions of the present Local Lymph Node Assay, Methyl-cyclopentanedione (CAS No. 765-69-5) tested at the maximum attainable concentration of 5 % (based on solubility) and at concentrations of 2.5 % and 1 % (w/v) as formulations in an appropriate vehicle (DMF) was shown to have no skin sensitization potential.

Categories Display