4-Pyrimidinecarboxamide, 2-(1-amino-1-methylethyl)-N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-6-oxo-

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse ear swelling test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

465-070-0

EC Name:

-

Cas Number:

518048-03-8

Molecular formula:

C16H19FN403

IUPAC Name:

2-(2-aminopropan-2-yl)-N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide

Details on test material:

L-000900405-000M004

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

The mice were treated by topical application of the test article concentrations, vehicle or control to the dorsum of each ear once daily for three consecutive days.

Study design: in vivo (LLNA)

Vehicle:

dimethyl sulphoxide

Concentration:

2.5% - 5% - 10%

No. of animals per dose:

5

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

The positive control, 25%HCA yielded a SI of 10.3, consistent with values obtained in the ICCVAM Validation Report.

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: see Remark

Remarks:

Treatment Stimulation Index DMSO - Vehicle : 1.0 25% HCA - Positive Control : 10.3 2.5% Test Article : 0.6 5% Test Article : 0.8 10% Test Article : 0.8 Note : a SI ≥ 3 indicates a sensitizing response.

Any other information on results incl. tables

Mean Number of Proliferating Cells in the Lymph Nodes of each Treatment Group

Treatment	Vehicle	Mean cell # (x10e3)	% BrdU+	# BrdU+
DMSO - Vehicle	-	2760	1.14	31298
25% HCA - Positive control	DMSO	13092	2.52	321949
2.5% Test Article	DMSO	2433	0.89	17497
5% Test Article	DMSO	3601	0.71	25528
10% Test Article	DMSO	3901	0.67	25119

The SI was calculated by dividing the mean number of proliferating lymph node cells# (BrdU+) from each Treatment Group by the mean number of proliferating cells from the DMSO Vehicle Group

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Topical application of the test article at 2.5%, 5%, and 10% resulted in a stimulation index less than 3 (SI ≤ 3.0), a negative result, and therefore this test article is not a dermal sensitizer in the Local Lymph Node Assay