Trans-2-[4'-[Difluor(3,4,5-trifluorphenoxy)methyl]-3',5'-difluor[1,1'-biphenyl]-4-yl]-5-propyl-tetrahydro-2H-pyran

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-12-22 to 2006-04-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002-04-24

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

92/69/EC

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

EC Number:

616-651-4

Cas Number:

787582-75-6

Molecular formula:

C26H2 lF702

Constituent 2

Reference substance name:

APUQU-2-F

IUPAC Name:

APUQU-2-F

Details on test material:

Batch: E06000594
Purity: (HPLC): 99.7 % (a/a)

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Strain: Albino rabbit, Crl:KBL (NZW), female (f)
Source: Charles River Wiga GmbH, Kißlegg
Age: Approx. 15 weeks

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: Aqua pro injectione

Controls:

no

Amount / concentration applied:

0.5 g of the test material mixed with several drops of Aqua pr injectione to ensure good skin contact. Single application

Duration of treatment / exposure:

4 hours

Observation period:

The rabbits were examined for skin alterations, behaviour and general condition 1 hour after removal of the patches, after 24, 48 and 72 hours, and then daily up to experimental day 8.

Number of animals:

3 females

Details on study design:

Prior to testing the pH of the preparation was determined with pH-test strips. The pH was found to be about 7. After that the test material was screened for its irritating potential using hen's egg test on the chorioallantoic membrane (HET-CAM). In the main study on primary skin irritation, 0.5 g of the test material, was mixed with some drops of Aqua pro injectione and ground in a mortar using a pestle to ensure good contact with the skin. Afterwards, the test material was spread onto 6 cm² patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 7 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

No skin irritating potential could be detected. According to EEC Directive 2001/59 the test item does not have to be classified as a skin irritant.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritating potential could be detected. According to CLP the test material should not be classified as a skin irritant.

Executive summary:

0.5 g of the test material was mixed with several drops of Aqua pro injectione to ensure good skin contact. The initial test with one animal and the confirmatory test with two further animals showed no signs of irritation at the treated areas following single application to the intact dorsal skin of rabbits for 4 hours under semiocclusive conditions. No signs of clinical toxicity were detected. All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous. Under the conditions of the present study no signs of irritation were seen.