2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 12, 1991 - January 1, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Buehler, E.V., Delayed Contact Hypersensitivity in the Guinea Pig., Arch. Dermat. 92: 171-175, 1965.

Deviations:

yes

Remarks:

The humidity was 52-80% rather than 40-70%. This is not thought to have affected the results.

GLP compliance:

not specified

Type of study:

Buehler test

Justification for non-LLNA method:

This test was performed before the LLNA method was adopted as the preferred method.

Test material

Test material information

Constituent 1

Reference substance name:

2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

EC Number:

268-706-3

EC Name:

2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

Cas Number:

68133-79-9

Molecular formula:

C15H24O

IUPAC Name:

2-(3,7-dimethylocta-2,6-dienyl)cyclopentan-1-one

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Davidson Mill Farm, Jamesburgh, New Jersey 08831, USA
- Weight at study initiation: 354 - 529 g
- Housing: Stainless steel wire mesh cages, elevated, 1-3 animals per cage
- Diet (e.g. ad libitum): Wayne Guinea Pig Formula ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3-21.9 degrees C
- Humidity (%): 52-80%
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark
- IN-LIFE DATES: From: December 4, 1991 To: January 9, 1992

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.4 mL

Day(s)/duration:

9 inductions were performed

Adequacy of induction:

highest technically applicable concentration used

Challenge

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

0.4 mL

Day(s)/duration:

24 hrs

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: A screening assessment was performed with animals exposed to 10, 25, 50, 75, and 100% test substance is white mineral oil. As there was only minimal reaction to the 100% substance (one animals showed exfoliation at 24 hrs after the third application), and no reactions at any of the lower concentrations, the full concentration of 100% was used.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 9
- Exposure period: 18 days
- Test groups: 10 animals
- Site: left flank
- Frequency of applications: every other day
- Duration: first induction 24 hrs, inductions 2-9 6 hrs
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 33
- Exposure period: 24 hrs
- Test groups: 10 animals
- Control group: 5 animals
- Site: right flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 hrs

Challenge controls:

5 naive animals

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (0.1% in 50% ethanol and 0.9% saline solution)

Results and discussion

Positive control results:

The positive control was determined to be a dermal sensitizer in albino guinea pigs.

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

other: 1st and 2nd readings

Hours after challenge:

48

Group:

test chemical

Dose level:

0.4 mL

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No reactions were noted after the challenge.

Results 2

Reading:

other: 1st and 2nd readings

Hours after challenge:

48

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

None

Results 3

Reading:

other: 1st and 2nd reading

Hours after challenge:

48

Group:

positive control

Dose level:

0.1% 1-chloro-2,4-dinitrobenzene

No. with + reactions:

6

Total no. in group:

6

Clinical observations:

Erythema (score of up to 3), edema (score of up to 2)

Any other information on results incl. tables

Skin Sensitization – Induction Phase: Reading after Each Application

 

Animal	1	2	3	4	5	6	7	8	9
1 – Erythema	1	0	0	1, Exfoliation	1, Exfoliation	2	Eschar	Eschar, Application site moved*	Eschar*
1-Edema	0	0	0	0	0	0	0	0	1
2-Erythema	1	0	0	1	1	1	1	2	1
2- Edema	0	0	0	0	0	0	0	1	1
3- Erythema	2	0	Exfoliation	1	1	2	2, Exfoliation	2, Exfoliation	2
3- Edema	0	0	0	0	0	0	0	1	2
4 – Erythema	2	1	1, Exfoliation	1, Exfoliation	1, Exfoliation	2	2	2	2, Exfoliation
4 – Edema	0	0	0	0	0	0	0	1	1
5 – Erythema	1	0	2, Exfoliation	2, Exfoliation	2, Exfoliation	2	Eschar	2, Application site moved	1
5 – Edema	0	0	0	0	0	0	0	1	1
6 – Erythema	1	0	0	1	1	2	2	Eschar	1, Application site moved
6 – Edema	0	0	0	0	0	0	0	0	0
7 – Erythema	0	0	0	0	0	1	2	1	1, Exfoliation
7 – Edema	0	0	0	0	0	0	0	0	0
8 – Erythema	0	0	0	2	2	2	2, Exfoliation	2, Exfoliation	2, Exfoliation
8 – Edema	0	0	0	0	0	0	0	1	1
9 – Erythema	0	0	0	1	1	2	2, Exfoliation	2, Exfoliation	2
9 – Edema	0	0	0	0	0	0	0	0	1
10 – Erythema	2	1	2, Exfoliation	1	1	1	2	2	2
10 - Edema	0	0	0	0	0	0	0	0	1

* Due to technician error, the original induction site was scored instead of the new test site.

Skin Sensitization Challenge Phase

 

Animal	24 hrs	48 hrs
Induced Animals
1 – Erythema	2	1
1-Edema	0	0
2-Erythema	2	1
2- Edema	0	0
3- Erythema	2	0
3- Edema	0	0
4 – Erythema	2	1
4 – Edema	0	0
5 – Erythema	3	2
5 – Edema	2	0
6 – Erythema	3	2
6 – Edema	2	0
7 – Erythema	2	1
7 – Edema	0	0
8 – Erythema	2	2
8 – Edema	1	0
9 – Erythema	3	2
9 – Edema	2	0
10 – Erythema	4	2
10 - Edema	2	1
Naïve Controls
1 – Erythema	1	0
1-Edema	0	0
2-Erythema	0	0
2- Edema	0	0
3- Erythema	0	0
3- Edema	0	0
4 – Erythema	0	0
4 – Edema	0	0
5 – Erythema	0	0
5 – Edema	0	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance is not sensitizing to the skin.

Executive summary:

The skin sensitization potential of the test substance was determined in a test using guinea pigs according to the method developed by Buehler. 10 guinea pigs were given 9 dermal induction exposures, and then after two weeks, given a challenge exposure to 0.4 mL of pure test substance. 5 naive control animals were used as a negative control, and a postive control experiment was performed as well. The postive and negative control results were valid. No skin reactions were seen in any animal in the test group during the challenge phase. The test substance is therefore not sensitizing to skin.