Bis(4-fluorophenyl) ketone

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-11-14 - 2006-01-06

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline comparable study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

This study was already available at the time of the dossier completion.

Test material

Test material information

Constituent 1

Reference substance name:

Bis(4-fluorophenyl) ketone

EC Number:

206-466-3

EC Name:

Bis(4-fluorophenyl) ketone

Cas Number:

345-92-6

Molecular formula:

C13H8F2O

IUPAC Name:

bis(4-fluorophenyl)methanone

Constituent 2

Reference substance name:

4,4'-Difluorobenzophenone

IUPAC Name:

4,4'-Difluorobenzophenone

Details on test material:

- Test substance: bis(4-fluorophenyl) ketone
- Supplier: Environmental Resource Management
- Purity: 99 %,
- Physical state: white powder
- Storage conditions: To be stored at room temperatur (18 - 25 °C), away from sources of heat and sunlight. Keep the container tightly closed.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ORGANISMS: 
- Source: Qianming Experimental Animal Feed Factory, Shenyang
- Strain: Dunkin-Hartley
- Sex: adult female rabbits
- Weight at study initiation: 260 - 330 g
- Controls: 10 animals; vehicle during induction
- Diet: ad libitum
- Water: ad libitum
- Temperature (°C): 22 °C +/- 4° C
- Humidity (%): 55 % +/- 10 %
- Illumination: natural lights
- Noiseness: <= 60 dB
- Number of test animals: 20
- Housing: Ten animals were housed in each 80 x50 x20 cm plastic cage; cages and feeders were changed and sanitized weekly

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: aceton

Induction 2

Concentration / amount:

Induction: 0.2 g / per animal
Challenge: 0.05 g / per animal; the challenge dose was near and under the highest Non-irritating dose.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: aceton

Challenge 2

Concentration / amount:

Induction: 0.2 g / per animal
Challenge: 0.05 g / per animal; the challenge dose was near and under the highest Non-irritating dose.

No. of animals per dose:

20 females (test) / 10 females (control)

Details on study design:

- Dose preparation and grouping
Four groups were selected including induced test substance group, non-induced test substance group, induced positive control group, and non-induced positive control group. In induced test substance group, the induction dose was 0.2 g/animal per time and challenge dose was 0.05 g/animal per time. 2,4-Dinitrochlorobenzene (DNCB) was employed as the positive control substance, diluted with 80 % ethanolto the concentrations of 1.0 % and 0.1 % as induction dose and challenge dose respectively.
The preliminary skin irritation test showed that the challenge dose of 0.05 g/animal per time was near and under the highest Non-irritating dose.
- Induction schedule
One day prior to being dosed, an area of 3 x 3 cm left back of each animal in induced test substance group was clipped using electrical hair clippers and then shaved using an electric shaver. Two layers of filter paper (2 x 2 cm) applied with 0.2 g of 4,4'-Difluorobenzophenone were plastered on the application site, then the application site was covered with one layer of polyethylene sheet and four layers of gauze. The entire trunk of each animal was then wrapped with a polyethylene sheet and secured with adhesive tape. After six hours, the patch was removed and the application site was rinsed completely with warm water. The same method was repeated on 7 and 14 days after the first administration. The same way was used in non-induction group, but acetone (0.2 ml) was applied.
- Challenge exposure
Thirteen days after completion of the closed patching in induction, an area of 3 x 3 cm right back of each animal in induced test substance group and non-induced test substance group was clipped using electrical hair clippers and then shaved using an electrical shaver. On the following day, 0.05 g of 4,4'-Difluorobenzophenone was plastered on the application site following the same way. After six hours, the patch was removed and the application site wa srinsed completely with warm water. All animals were examined continuosly for twelve days. If no skin sensitization was observed, another challenge exposure was performed again in induced test substance group 28 days after the completion of the closed patching in induction.
- Positive control exposure
Induced positive control goup: 0.2 ml of 1.0% DNCB solution applied in induction exposure and 0.2 ml of 0.1% DNCB solution applied in challenge exposure.
Non-induced positive control group: 0.2 ml of 80% ethanol solution applied in induction exposure and 0.2 ml of 0.1% DNCB solution applied in challenge exposure. The same methods were performed as the methods in the test substance group.
- Measurement of body weight
The body weight of all animals were mesured on the first day of induction exposure at the termination of the test.
- Clinical test
Animals were observed for their clinical signs once every day.
- Skin reaction
The plasterd sites for challenge were observed for skin reaction 24 and 48 hours after patch removal.
Examination:
0 = no reaction
1= scatter mild redness
2 = moderate redness
3 = intense redness and swelling

Challenge controls:

Treatment: vehicle during induction

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorobenzene (DNCB)

Results and discussion

Positive control results:

- Induced positive control group: both erythema and edema were seen on the skin regions of three animals, thereinto about half with edema were seen on the skin regions of two animals where DNCB had been applied for one challenge throughout the observeation.
- Non-induced positive control group: no abnormalities were observed on the skin regions of all animals where DNCB had been applied for once challenge throughout the observation.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.05 g

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no sensitization

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.05 g. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no sensitization.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.05 g

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no sensitization

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.05 g. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no sensitization.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Based on the results, the test substance 4,4'-Difluorobenzophenone showed no skin-sensitizing effect on guinea pigs under the conditions of the study.

Executive summary:

In accordance to the Buehler Test, 4,4'-Difluorobenzophenone was tested for its skin sensitizing effect on adult guinea pigs. 50 female animals were selected and allocated in four groups randomly, twenty of them in induced test substance group, each ten of them in non-induced test substance group, as well as in induced positive control group and in non-induced positive control group. 2,4 -Dinitrochlorobenzene (DCNB) were employed as positive control substance. Dosage: 0.2 g test substance per animal for induction and 0.05 g test substance per animal for challenge. The challenge dose was near and under the highest Non-Irritating dose. The clinical signs and skin reactions on the infected sites of all animals in four groups were observed, and the sensitization rates were claculated at 24 h and 48 h after removal of the patch.

Acoording to the results of the test, the sensitizing rates of animals in induced test substance group and induced positive control group were 0% and 100%, respectively. Therefore, based on the study results, the test substance 4,4'-Difluorobenzophenone was concluded to have no skin-sensitizing effect on guiena pigs under the experimental conditions of this study.