Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 31, 2015 - January 27, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted on July 28, 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
4-[3,5-difluoro-4-(trifluoromethoxy)phenyl]-3-fluoro-4'-[(1s,4r)-4-propylcyclohexyl]-1,1'-biphenyl
EC Number:
610-847-3
Cas Number:
524709-77-1
Molecular formula:
C28H26OF6
IUPAC Name:
4-[3,5-difluoro-4-(trifluoromethoxy)phenyl]-3-fluoro-4'-[(1s,4r)-4-propylcyclohexyl]-1,1'-biphenyl
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
0.5 g of the solid test item was applied per animal. Before application, the test item was grounded in a mortar using a pestle and mixed with liquid paraffin.
For the treatment of animal no. D26580, 0.70 g of the test item was moistened with 0.38 g of liquid paraffin. 0.77 g of the test item preparation was applied to the animal.
For the treatment of animal nos. D26556 and D26589, 1.40 g of the test item was moistened with 0.71 g of liquid paraffin. 0.75 g of the test item preparation was applied to each animal, respectively.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, France
- Age at study initiation: 12 - 13 weeks
- Weight at study initiation: 2.67 - 2.78 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.2 - 19.1°C
- Humidity (%): 44.3 - 74.3%
- Photoperiod (hrs dark / hrs light): 12hrs dark / 12hrs light

IN-LIFE DATES: From: day 1 To: day 8

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Liquid paraffin
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test item was applied per animal.

VEHICLE
Designation: Art. 1.07174
Synonym: Liquid paraffin
Supplier: Merck KGaA, Germany
Batch: K45409474
Released until: April 30, 2019


Duration of treatment / exposure:
4 hours
Observation period:
8 days
Number of animals:
3 females
Details on study design:
TEST SITE
The backs and flanks of all rabbits were shorn 24 hours before administration of the test item with electric clippers equipped with a 1/10 mm shaver head. Only animals with healthy, intact skin were used for the study.
The test item was applied to a gauze patch measuring 6 cm2 (Verbandmull ZZ; Paul Hartmann AG, Heidenheim, Germany). This patch was fixed at the left half of the animals' back. During the time of exposure (4 hours), the application site was covered with a non-irritating tape (Fixomull® stretch; BSN medical GmbH, Hamburg, Germany). After the exposure time, the patch was removed and any residues of the test item were wiped off with a dry cloth.


REMOVAL OF TEST SUBSTANCE
- Method: wiped off
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Local irritations or any clinical systematic alteration were evaluated immediately after patch removal, then 60 minutes, 24 hours, 48 hours and 72 hours thereafter according to Draize (Draize, 1959) and recorded individually for each animal on a record sheet. A daily evaluation was continued up to study day 8.

SCORING SYSTEM:
- Method of calculation: according OECD 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No clinical symptoms and no signs of skin irritation were observed.
Other effects:
- Other adverse local effects: no
- Other adverse systemic effects: no

Any other information on results incl. tables

Objective

The objective of the present study was to investigate the primary skin irritating potential of the test item in rabbits.

Study design

The test item was mixed with liquid paraffin to ensure good contact with the skin. Afterwards, the test item was spread onto patches and applied to the healthy, intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. Untreated shaven skin areas of the rabbit served as control. The first examination of the treated and untreated skin was performed immediately after patch removal and then after 60 minutes. Thereafter, examinations were performed daily for further 7 days.The study was performed initially with one animal, followed by the confirmatory test with two further animals.

Results

No mortality occurred during the experimental phase of the study.

The body weight development of the treated rabbits was inconspicuous.

No clinical symptoms and no signs of skin irritation were observed.

Conclusions

Under the conditions of the present study, no skin irritation potential was detected for the test item.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the present study, no skin irritation potential was detected for the test item.
Executive summary:

This study was performed according to GLP and methods applied are fully compliant with OECD TG 404. Under the conditions of the present study, no skin irritation potential was detected for the test item.