Trans-2-[4'-[Difluor(3,4,5-trifluorphenoxy)methyl]-3',5'-difluor[1,1'-biphenyl]-4-yl]-5-propyl-tetrahydro-2H-pyran

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-10-19 to 2007-11-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992-07-17

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

96/54/EC

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

This study was available before the implementation of REACH.

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

EC Number:

616-651-4

Cas Number:

787582-75-6

Molecular formula:

C26H2 lF702

Constituent 2

Reference substance name:

APUQU-2-F

IUPAC Name:

APUQU-2-F

Details on test material:

Batch: E06000594
Purity (GC): 99.9 %

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Guinea pig, HsdPoc:DH, females
Breeder: Harlan Winkelmann GmbH, Borchen
Age: about 4 weeks

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Induction 2

Concentration / amount:

undiluted

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Challenge 2

Concentration / amount:

undiluted

No. of animals per dose:

Pretest: 5 females
Group 1: 5 females (negative control group)
Group 2: 10 females (test material group)

Details on study design:

The test item was investigated for skin sensitizing properties in the guinea pig maximization test according to Magnusson and Kligman (1969). A pre-test with intradermal or topical administrations of the vehicles and the test material was performed for selection of the concentrations suitable for the main study. In the main study, 5 females were treated with the vehicles liquid paraffin (intradermal) and polyethylene glycol 400 (group 1), 10 females were treated with the test material (group 2). Induction included intradermal injection of test material preparation in liquid paraffin (10 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene gylcol 400 (200 g/L) for 48 hours on experimental day 8. Challenge by topical application of the test material preparation in polyethylene glycol 400 (100 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 and 72 hours after start of the treatment.

Challenge controls:

Vehicle polyethylene glycol 400 (PEG 400) only.

Positive control substance(s):

yes

Remarks:

α-Hexylcinnamaldehyde periodically investigated

Results and discussion

Positive control results:

The sensitivity of the test system is only checked periodically with α-Hexylcinnamaldehyde. The data of the latest investigation are provided in the study report. At that time a positive reaction of 50% has been determined after induction.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 g/L

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

Results 2

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 g/L

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Results 3

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

100 g/L

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: None.

Results 4

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100 g/L

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 100 g/L. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.

Results 5

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

No. with + reactions:

5

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the given experimental conditions, the test material induced no reactions. According to CLP, the test item is not to be classified as sensitizer.

Executive summary:

The test item was investigated for skin sensitizing properties in the guinea pig maximization test according to Magnusson and Kligman (1969). A pre-test with intradermal or topical administrations of the vehicles and the test material was performed to select the concentrations suitable for the main study. In the main study, 5 females were treated with the vehicles liquid paraffin (intradermal) and polyethylene glycol 400 (group 1), 10 females were treated with the test material (group 2). Induction included intradermal injection of test material preparation in liquid paraffin (10 g/L with and without Freund's complete adjuvant) on experimental day 1, and topical application of test material preparation in polyethylene gylcol 400 (200 g/L) for 48 hours on experimental day 8. Challenge by topical application of the test material preparation in polyethylene glycol 400 (100 g/L) for 24 hours was performed two weeks after topical induction and readings were taken at 48 and 72 hours after start of the treatment. After intradermal injection, the common signs of irritation after injection of Freund's complete adjuvant were observed. The injection sites were swollen and red with subsequent scab formation. The challenge was performed on the right side of the animals. Group 1 (negative control group): After challenge with polyethylene glycol 400, no erythema or edema was observed. A single treatment was performed with test material (100 g/L preparation in polyethylene glycol 400) to exclude primary irritation of the test material concentration. No positive reactions were observed in the treated areas at any time point. Group 2 (test material group): After challenge with test material (100 g/L preparation in polyethylene gylcol 400) no positive skin reactions were observed. This results in 0 % positive reactions after challenge. After challenge, no positive reactions were observed in the areas treated with polyethylene glycol 400 alone at any time. The clinical behaviour of the guinea pigs was normal during the experimental part and all animals survived. The body weight development corresponded to that of the animals of the vehicle group.