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

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001-03-02 to 2001-05-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

07-1992

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was performed in 2001

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

604-593-2

Cas Number:

147622-85-3

Molecular formula:

C18 H22 F2 O

IUPAC Name:

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

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: 6 weeks
- Weight at study initiation: 315 - 384 g
- Housing: two animals per Makrolon cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22
- Humidity (%): 52 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 25

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

paraffin oil

Concentration / amount:

Group 1 (control): cranial 0.1 mL FCA + NaCl solution; medial 0.1 mL vehicle; caudal 0.1 mL FCA + NaCl solution
Group 2 (test item): cranial 0.1 mL FCA + NaCl solution; medial 0.1 mL test item (5 g/L vehicle); caudal 0.1 mL FCA with test item + NaCl solution (5 g test item/L preparation)

Day(s)/duration:

day 1

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Induction 2

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

Filter patch soaked with 1 mL of the test item preparation or vehicle.
Group 1: liquid paraffin
Group 2: Test item (200 g/L vehicle)

Day(s)/duration:

day 8 (over 48 hours)

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Challenge

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Concentration / amount:

Filter paper soaked with 0.5 mL of the test item preparation or vehicle
Group 1: liquid paraffin
Group 2: Test item (10 g/L vehicle)

Day(s)/duration:

day 22 (over 24 hours)

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Pretest: 5 f
Group 1 (vehicle controls): 10 f
Group 2 (test item): 20 f

Details on study design:

During the induction phase, the guinea pigs were examined on days 2, 3, 7, 11, 12, 15, and 22 of the experimental part for local skin reactions.
Behavior and general condition of all animals were monitored daily.
The challenge sites were investigated for reactions 48 hours after start of the challenge. Further inspections followed 72 hours after start of the challenge.
Body weights were determined prior to the start of the experimental part, on experimental days 8, 15, 22, and at the end of the experimental part.

Positive control substance(s):

yes

Remarks:

The control was carried out with alpha-Hexylcinnamaldehyde

Results and discussion

Positive control results:

see above

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

other: 1st and 2nd reading (48 and 72 hrs after challenge)

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

other: 1st and 2nd reading (48 and 72 hrs after challenge)

Hours after challenge:

48

Group:

test chemical

Dose level:

1 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

Study design

The test item was evaluated for skin sensitizing properties in the guinea pig maximization test according to MAGNUSSON and KLIGMAN (1969). 10 female guinea pigs in the negative control group (group 1) treated with the vehicle liquid paraffin and 20 females in the test material group (group 2) were investigated. Induction included intradermal injection of test material preparation (5 g/L with and without FCA) on experimental day 1, and topical application of test material preparation (200 g/L) on day 8 of the experimental part. Challenge by topical application of the test material preparation (10 g/L) was performed two weeks after topical induction.

Results

After challenge no positive reactions in the test material treated skin sites at both readings were seen.

Conclusion

Under the given experimental conditions, the test item showed no positive responders and has not to be classified as a sensitizer.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the given experimental conditions, the test item showed no positive responders and has not to be classified as a sensitizer.