Flufenamic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

other information

Study period:

Feb 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well reported GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

Flufenamic acid

EC Number:

208-494-1

EC Name:

Flufenamic acid

Cas Number:

530-78-9

Molecular formula:

C14H10F3NO2

IUPAC Name:

2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid

Details on test material:

Flufenaminsäure, yellow powder, Batch BXR2GXS, content 99.0%

In vivo test system

Test animals

Species:

mouse

Strain:

NMRI

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

0 (vehicle control), 2, 10 and 50%

No. of animals per dose:

6 females

Results and discussion

In vivo (LLNA)

Results

Parameter:

SI

Remarks on result:

other: NMRI mice did not show an increase in the stimulation indices for cell counts or for weights of the draining lymph nodes.

Any other information on results incl. tables

The "positive level" of ear swelling (i.e. increase of about 10% of the control values) has not been reached or exceeded in any dose group. However, there was a statistical significant increase after application of 10% test item. A significant increase compared to vehicle treated animals regarding ear weight was detected in the low and mid dose group.

The body weights of the animals were not affected by any treatment.

Tabular summary of the LLNA/IMDS results:

	Direct LLNA		Ear swelling (in 0.01 mm)			Ear weight (in mg per 8 mm diameter punch)
Dose (%)	Weight index (mean +/- SD in %)	Cell count index (mean +/- SD in %)	day 1 (mean +/- SD in %)	day 4 (mean +/- SD in %)	Index day 4	day 4 (mean +/- SD in %)	Index day 4
0 (DMF)	1.00 +/- 16.33	1.00 +/- 25.06	17.75 +/- 4.88	17.25 +/- 6.60	1.00	11.09 +/- 4.85	1.00
2	1.10 +/- 23.94	1.14 +/- 29.26	17.75 +/- 4.88	17.50 +/- 5.71	1.01	12.18* +/- 5.88	1.10
10	1.25 +/- 14.24	1.19 +/- 26.18	18.08 +/- 5.51	18.67* +/- 5.75	1.08	13.18* +/- 9.09	1.19
50	0.95 +/- 32.65	0.91 +/- 48.10	17.92 +/- 4.43	17.00 +/- 5.61	0.99	10.65 +/- 6.63	0.96

* statistically significant increase (p <= 0.05)

Applicant's summary and conclusion

Executive summary:

To determine the skin-sensitizing properties of Flufenamic acid the LLNA was performed on female NMRI mice according to OECD guideline 429 and EPA OPPTS 870.2600. The study was conducted with the following test substance concentrations: 2, 10 and 50%

The results showed that the test item has no sensitising potential in mice after dermal application of up to and including 50% concentration. However, the study does point to a non-specific (irritating) immunostimulating potential of the test item since a significant increase compared to vehicle treated animals regarding ear swelling was detected in the mid dose group. In addition, a statistically significant increase was detected for the ear weight in the low and mid dose group. It must be concluded that the test item has an irritating potential starting at the lowest concentration tested, i.e. 2%.