4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Apr 2015 to 19 Apr 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

This in vivo study was conducted to meet the data requirements of regulations not related to REACH in non-EEA countries.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Cas Number:

2061933-85-3

Molecular formula:

C23H19Cl2F4N3O4

IUPAC Name:

4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl)-N-(2-ethyl-3-oxo-1,2-oxazolidin-4-yl)-2-methylbenzamide

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Age at study initiation: 12 weeks
- Weight at study initiation: 3113 – 3282 g
- Housing: Individual caging
- Diet: ad libitum.
- Water: Tap water, from an automatic system, ad libitum
- Acclimatisation period: 13 and 15 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.1 – 22.4
- Humidity (%): 28 – 53
- Air changes (per hour): 15 - 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14 Apr 2015 To: 19 Apr 2015

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

STUDY DESIGN
In a primary skin irritation study, the test substance was administered at 0.5 g / animal, the dose specified in the test guidelines for a solid test substance. Initially, a single animal was treated. As neither a corrosive effect nor a severe irritant effect were observed after the 24-hour observation, the test was completed using the 2 remaining animals with an exposure period of 4 hours.
The viability/mortality was recorded daily from the day of application of the animals to the termination of test.
Clinical signs were recorded daily and body weights were recorded on the day of application and at termination of observation.
The animals were checked daily for signs of systemic toxicity.

TEST SITE
- Area of exposure: Approximately 24 hours prior to the test the hair was clipped from the back and flanks of the animals with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). Animals with overt signs of skin injury or marked irritation, which may have interfered with the interpretation of the results, were not used in the test.
- Type of wrap: On the day of treatment, 0.5 g of test substance was placed on a surgical gauze pad (ca. 2.5 cm x 2.5 cm) and sufficient water was added to dampen the material to ensure good contact with the skin. This gauze pad was applied to the intact skin of the clipped area and was kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunk of the animals was then wrapped with plastic wrap held in place with an elastic stocking.

REMOVAL OF TEST SUBSTANCE
- Duration of treatment: 4 hours
- Washing: The dressing was then removed and the skin was flushed with lukewarm tap water to clean the application site.

OBSERVATION TIME POINTS
- Approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test substance.  

SCORING SYSTEM:
- Method of calculation: Draize scoring system. The primary irritation index was calculated by totalling the mean cumulative scores at 24, 48 and 72 hours for all animals and then dividing by the number of data points.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

5

Results 2

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No local dermal signs were observed in the treated animals throughout the study.

Other effects:

CLINICAL OBSERVATIONS
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

DURATION OF THE IN-LIFE PHASE
As no clinical signs were observed at 72 hours after patch removal, the study was terminated after the 72 hours observation.

BODY WEIGHT
The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The application of the test substance did not result in any signs of skin irritation.
Under the conditions of this study, the test substance is considered to be "not irritating" to the rabbit skin according to the Draize classification criteria.

Executive summary:

The primary skin irritation potential of the test substance was investigated according to the GLP compliant OECD 404 (2002), OPPTS 870.2500 (1998) and EC No 440/2008, B.4 (2008). Young adult New Zealand White rabbits (3 males) were dermally exposed to 0.5 g of test substance, applied to the intact shaved skin under a semi-occlusive dressing, for 4 hours. Skin reactions were scored at 1, 24, 48 and 72 hours after removal of the dressings according to the Draize Scoring System. The Primary Irritation Index (PII) was calculated.

No local dermal signs were observed in the treated animals throughout the study. No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. As no clinical signs were observed at 72 hours after patch removal, the study was terminated after 72 hours observation. The body weights of all rabbits were considered to be within the normal range of variability. The application of the test substance  did not result in any signs of skin irritation.

Under the conditions of this study, the test substance is considered to be not irritating to the rabbit skin according to the Draize classification criteria.