1-Ethoxy-2,3-difluoro-4-[trans-4-(trans-4-propylcyclohexyl)-cyclohexyl]-benzene

Endpoint summary

Description of key information

No skin irritating potential could be detected for the test item.

The test item showed no relevant eye irritating potential.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 23, 2007 - July 13, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 15 weeks
- Weight at study initiation: 3.14 - 3.35 kg
- Housing: separately in special rabbit cages (manufacturer: Becker, type K99/30 KU)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 19
- Humidity (%): 45 - 53
- Photoperiod (hrs dark / hrs light): 12/12

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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g per animal

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Before application, the test material was mixed with some drops of Aqua pro injectione and ground in a mortar using a pestle.

VEHICLE
Name: Aqua pro injectione
Manufacturer: Merck KGaA, Darmstadt
Batch: 189
Released until: June 08, 2009

Duration of treatment / exposure:

4 hours

Observation period:

8 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: left side of the animal back
- Type of wrap if used: self-adhesive fabric (Fixomull stretch, Beiersdorf)

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

OBSERVATION TIME POINTS
1 hour after removal, after 24, 48, 72 hours, and then daily up to experimental day 8

SCORING SYSTEM:
- Method of calculation: according to OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No skin irritating potential could be detected.

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritating potential could be detected for the test item.

Executive summary:

A study was performed according to GLP and methods applied were fully compliant with OECD 404. The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of irritation were seen. Body weight development of the treated rabbits was inconspicuous. Thus, no skin irritating potential could be detected for the test item.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 5, 2007 - September 26, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

Official Journal of the European Communities L152, 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Charles River Wiga GmbH, Kisslegg
- Age at study initiation: appr. 26 weeks
- Weight at study initiation: 3.51 - 4.52 kg
- Housing: The animals were kept separately in special rabbit cages (manufacturer: Becker, type K99/30 KU) placed on mobile racks.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20
- Humidity (%): 52 to 75
- Air changes (per hr): not specified

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

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g per animal

Observation period (in vivo):

24, 48, and 72 hours, then daily up to day 8 of the experimental part

Number of animals or in vitro replicates:

3 female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according OECD-Guideline

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. In two animals redness (score 1) was observed one hour after treatment. No abnormalities were detected in the untreated eyes.

Other effects:

none

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed no relevant eye irritating potential.

Executive summary:

The test material was tested for its eye irritating properties according to OECD 405 under GLP conditions. Prior to testing, the hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. The test for primary eye irritation was performed initially with one animal and followed by the confirmatory test with two further animals. For the test of primary eye irritation, the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations of the eyes were performed daily for a further 7 days. No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. In two animals redness (score 1) was observed one hour after treatment. No abnormalities were detected in the untreated eyes. No relevant eye irritating potential could be detected. The test material should not be classified as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

A study was performed according to GLP and methods applied were fully compliant with OECD TG 404. The test material was mixed with some drops of Aqua pro injectione to ensure good contact with the skin. Afterwards, the test material was spread onto patches and applied to the intact skin of previously shaven rabbits for 4 hours under semi-occlusive conditions. The study was performed initially with one animal and followed by the confirmatory test with two further animals. The first examination of the treated skin followed 1 hour after patch removal. Thereafter, examinations were performed daily for a further 7 days. Under the conditions of the present study, no signs of irritation were seen. Body weight development of the treated rabbits was inconspicuous. Thus, no skin irritating potential could be detected for the test item.

 

Eye irritation

The test material was tested for its eye irritating properties according to OECD 405 under GLP conditions. Prior to testing, the hen's egg test on the chorioallantoic membrane was performed and no irritating potential could be detected. The test for primary eye irritation was performed initially with one animal and followed by the confirmatory test with two further animals. For the test of primary eye irritation, the test material was applied into the conjunctival sac of rabbits. The first examination of the eyes followed 1 hour after instillation. The other examinations of the eyes were performed daily for a further 7 days. No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. In two animals redness (score 1) was observed one hour after treatment. No abnormalities were detected in the untreated eyes. No relevant eye irritating potential could be detected. The test material should not be classified as an eye irritant.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item does not require classification for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP).