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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-05-27 to 2004-09-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: SPL Standard Test Method 595.12
Deviations:
yes
Remarks:
1) Insufficient information on the test substance, test animals, methodological details and information on results presented; 2) No positive control substance tested.
GLP compliance:
no
Remarks:
The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance is made for the study.
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
1-benzyl-4-piperidone
EC Number:
222-782-4
EC Name:
1-benzyl-4-piperidone
Cas Number:
3612-20-2
Molecular formula:
C12H15NO
IUPAC Name:
1-benzylpiperidin-4-one
Test material form:
liquid
Details on test material:
- Identification: JNJ-728195-AAA
- Physical state: liquid
- Appearance: clear yellowish liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: no data
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL: No data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING: No data

In vivo test system

Test animals

Species:
mouse
Strain:
CBA/Ca
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 2003-05-27 To: 2003-06-30

Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
5%, 10%, 25%
No. of animals per dose:
Four animals per dose
Details on study design:
RANGE FINDING TESTS: Yes, no deaths or toxicity signs were observed at the preliminary sighting tests at concentrations of 25, 50 and 100%.

MAIN STUDY
- Name of test method: SPL Standard Test Method 595.12 (mouse local lymph node assay)
- Criteria used to consider a positive response: No data

TREATMENT ADMINISTRATION:
- Volume of treatment: 50 micrograms (25 micrograms/ear)
-Application location: topical application to dorsal surface of ear
-Control group: 4 animals iwth acetone/olive oil 4/1 alone.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
other: 2,4-dinitrobenzenesulfonic acid, sodium salt 1%, 10%, 20% v/v in 1% pluronic F-68 in distilled water
Statistics:
no data

Results and discussion

Positive control results:
Not applicable

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
3.51
Test group / Remarks:
4 animals in 5 % v/v in acetone/olive oil 4:1 group
Parameter:
SI
Value:
6.53
Test group / Remarks:
4 animals in 10 % v/v in acetone/olive oil 4:1 group
Parameter:
SI
Value:
14.26
Test group / Remarks:
4 animals in 25 % v/v in acetone/olive oil 4:1 group
Cellular proliferation data / Observations:
CELLULAR PROLIFERATION DATA: no data

DETAILS ON STIMULATION INDEX CALCULATION: see above

EC3 CALCULATION: no EC3 value could be calculated based on the classical linear method as the SI values at all concentrations were > 3
Ryan et al. (2007)* described a method for calculation of an extrapolated EC3 value based on following formula:
EC3ex = 2^{log2(c) + (3-d)/(b-d) x [log2(a)-log2(c)]}
Based on the results of this LLNA study the results are the following:
EC3ex = 4.44
with a=10, b=6.53, c=5, d=3.51

As described by Ryan et al., two aspects of data quality can affect the accuracy of potency classification of the datapoints used: the slope ratio and the value of the lowest SI obtained and the closest above 3%.
- The dose response curve location of the extrapolation datapoints was determined by calculating a ratio of the slopes between the second and third and the first and second points. A higher degree of accuracy was found in the extrapolated values derived from curves with slope ratios below 2, indicating that the use of points which lie on the linear portion of the dose response curve results in more reliable potency class estimations. A significant correlation was also found between the lowest SI value and the accuracy of EC3 values derived by the log-linear extrapolation. For this substance the slope ratio was calculated to be 0.85.
- The reliability of the extrapolated values was found to be greater when the lower SI value used in the calculation approached 3 which is the case for this substance.
Of these two parameters, it appears that the slope ratio is more important to consider.
Both conditions related to data quality have been met for this substance which means the potency calculation is considered accurate.

* Ryan CA, Chaney JG, Gerberick GF, Kern, PS, Dearman RJ, Kimber I and Basketter DA. Extrapolating Local Lymph Node Assay EC3 Values To Estimate Relative Sensitizing Potency. Cutaneous and Ocular Toxicology (2007); 26(2): 135-145.

CLINICAL OBSERVATIONS: no data

BODY WEIGHTS: no data

Any other information on results incl. tables

Positive Control Local Lymph Node Assay in the Mouse (2004)

Start Date

Finish Date

Test Material

Concentration

Vehicle

Stimulation Indexa

Classificationb

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.40, 2.23, 6.09

Positive

29/04/2004

05/05/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

acetone/olive oil 4:1

1.74, 2.20, 8.89

Positive

14/10/2004

26/10/2004

α‑Hexylcinnamaldehyde, tech., 85%

5%, 10%, 25% v/v

tetrahydrofuran

1.97, 3.71, 7.82

Positive

29/09/2004

05/10/2004

2,4‑Dinitrobenzenesulfonic acid, sodium salt

1%, 10%, 20% v/v

1% pluronic F-68

in distilled water

1.03, 4.41, 13.55

Positive

27/10/2004

02/11/2004

α‑Hexylcinnamaldehyde, tech., 85%

10%, 25%, 50% v/v

cottonseed oil

1.52, 2.63, 5.07

Positive


a=        Ratio of test to control lymphocyte proliferation

b=        Stimulation index greater than 3.0 indicates a positive result

* =        Standard Test Method 595 (Pooled nodes)

·=        Standard Test Method 599 (Individual nodes)

Applicant's summary and conclusion

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
The test item was considered to be a skin sensitiser category 1B based on the extraoplated EC3 value of 4.44 as established using the data of this LLNA study and the method described by Ryan et al., 2007.