tert-butyl {(1S)-2-[(1S,3S,5S)-3-cyano-2-azabicyclo[3.1.0]hex-2-yl]-1-[3-hydroxyadamantan-1-yl]-2-oxoethyl}carbamate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 2002

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

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

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid - liquid: suspension

Details on test material:

Batch #2D48725 Lot002

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

10%,, 25% and 50% (M/v)

No. of animals per dose:

4

Details on study design:

4 Groups of four female mice were assigned to study in total. The first group were the control group (vehicle control = DMF) and the other 3 groups were assgined for the 3 differenct concentrations of the test article (10%, 25% and 50%)
Eadh group of four female mice was subjected to application of the vehicle or one of the test formulations to the outer aspect of teh auditory pinnae, once daily on Days 1, 2 and 3.
On day 6 the mice were placed under an infra-red heat lamp, to cause dilation of the peripheral blood vascalature and thus facilitate intravenous dosing. EAch mouse was transferred to a cylindrical restrainer. A plastic syringe and fine gauge hypodermic needle were used to administer 0.25 mL of phosphate buffered saline incorporating 20 UCi of tritiated tymidine into a tail vein of each mouse.
After treatment the mice were returned to the group cage
Approx 5 hours after intravenous injected of the tritiated thumidine, all mice were killed by Halothane asphyxiation, Killing was organised to minimse the interval between death and the recovery of the auricular lymph notes to no more than 15 minutes.

Results and discussion

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: The theshold level for the Prolifereation Index to be considered a positive indicator of moderate to severe potential to cause skin sensitisation is 3.0. PI = Test Group CLM value/Control Group CLM value

Any other information on results incl. tables

Sample Id	No of sites yielding lymph nodes	CPM	CPM per node	Proliferation Index (PI)
Scintillation Fluid (blank)	-	11.33	-	-
Scintillation fluid with5% m/v trichloroacetic acid	-	189.84	-	-
Vehicle control (DMF)	8	1397.82	174.73	-
BMS 528235 -01, 10% m/v	8	1109.15	138.64	0.8
BMS 528235 -01, 25% m/v	8	824.21	103.03	0.6
BMS 528235 -01, 50% m/v	8	1042.56	130.32	0.7

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The proliferation index for all three dose levels was less than 3.0, indicating that the test article does not have a strong sensitising potential.

Executive summary:

The Local Lymph Node Assay demonstrated that BMS 528235 -01 does not have a potential to cause skin sensitisation.