4-[4-(3,4-Difluorophenyl)-cyclohexyl]-cyclohexanone

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 20, 2003 - March 17, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex to Directive 92/69/EEC:
Annex to Commission Directive of 31st July 1992 adapting to technical progress for the seventeenth time Council Directive 67/ 548/ EEC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances
Official Journal of the European Communities L383 A, Vol. 15, 29. December 1992.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4'-(3,4-difluorophenyl)-[1,1'-bi(cyclohexane)]-4-one

EC Number:

605-495-2

Cas Number:

167948-98-3

Molecular formula:

C18H22F2O

IUPAC Name:

4'-(3,4-difluorophenyl)-[1,1'-bi(cyclohexane)]-4-one

Test animals

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: 3.10 kg (range from 2.81 to 3.31)
- 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): 19 - 20°C
- Humidity (%): 41 - 54%
- 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:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL per animal

Duration of treatment / exposure:

4 hours

Observation period:

24, 48, 72 hours after removal of patches

Number of animals:

3 female rabbits

Details on study design:

TEST SITE
- Area of exposure: back
- Type of wrap if used: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 4 h

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 the guideline and Draize:
Grading scale for evaluation:
Erythema and eschar formation: Scores
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema:3
Severe erythema to eschar formation preventing grading of erythema: 4

Maximum possible: 4

Edema formation: Scores
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (raised approx. 1 mm): 3
Severe edema (raised more than 1 mm and extending beyond area of exposure): 4

Maximum possible: 4

Total possible irritation score (maximum): 8

Mean score = Mean grading for erythema or edema of all the rabbits per time point
Mean cumulative score = Mean grading of all readings for erythema and edema per time point
Mean score per animal = Mean grading for each animal of erythema or edema (24, 48, and 72 hours after removal of the patches)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No skin irritating potential could be detected.

Other effects:

None

Any other information on results incl. tables

Clinical findings

After a single application to the intact dorsal skin of rabbits, for a 4 hours period of exposure under semiocclusive conditions, no signs of irritation were observed in the treated areas. No signs of clinical toxicity were detected.

Mortality

All animals survived the observation period.

Body weight

Body weight development of the treated rabbits was inconspicuous.

The individual local findings were:

Animal No.		Local findings on day
		1	2	3	4	5	6	7	8
		(1h)	(24h)	(48h)	(72h)
3	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
9	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0
11	Erythema	0	0	0	0	0	0	0	0
	Edema	0	0	0	0	0	0	0	0

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No skin irritating potential could be detected.

Executive summary:

The purpose of this assay was to identify the skin irritation/corrosion potential of the test item when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man. The test material was spread onto patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Then, examinations were performed daily for further 7 days. Under the conditions of the present study no signs of irritation were seen. The evaluation of all animals yields a zero mean score. The test item was not irritating to the skin in this assay.