4-propylcyclohexanone

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-04-24 to 1990-06-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Type of study:

open epicutaneous test

Justification for non-LLNA method:

The guinea pig test method described in OECD TG 406 provide suitable information for hazard identification.

Test material

Test material information

Constituent 1

Reference substance name:

4-propylcyclohexanone

EC Number:

406-810-4

EC Name:

4-propylcyclohexanone

Cas Number:

40649-36-3

Molecular formula:

C9H16O

IUPAC Name:

4-propylcyclohexan-1-one

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Iva: PDH

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: no information
- Age at study initiation: about 4 weeks
- Weight at study initiation: 212 (186-251) g
- Housing: individual in Makrolon cages type IV
- Diet: Altromin Standard Diet TPF 3012; ad libitum
- Water: Tap water; ad libitum
- Acclimation period: 7 days
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-30 °C
- Humidity (%): 40-62%
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, open

Vehicle:

paraffin oil

Concentration / amount:

0.1 mL/ 3 and 10% test item

Day(s)/duration:

once daily for 21 days

Adequacy of induction:

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

Challenge

Challenge 1

No.:

#1

Route:

epicutaneous, open

Vehicle:

paraffin oil

Concentration / amount:

1, 3 and 10 % test item

Day(s)/duration:

day 22

Adequacy of challenge:

highest non-irritant concentration

Challenge 2

No.:

#2

Route:

epicutaneous, open

Vehicle:

paraffin oil

Concentration / amount:

1, 3 and 10% test item

Day(s)/duration:

day 36

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

6

Details on study design:

RANGE FINDING TESTS: According to the recommendations of KLECAK a pretest to determine the threshold concentration after single application was done with 3, 10 and 30 % preparations. The concentrations of 10 and 30 % did induce skin irritation and thus the concentrations of 3% and 10% were choosen as concentrations for the sensitization study.

MAIN STUDY
A. INDUCTION EXPOSURE
- Test groups: 0.1 mL test material preparation
- Control group: treated with vehicle (liquid paraffin) only
- Site: shaved back
- Frequency of applications: Once daily
- Duration: 21 days
- Concentrations: 3% and 10% (group 3 and 4)

B. CHALLENGE EXPOSURE
- No. of exposures: single
- Day(s) of challenge: day 22 (challenge I) and day 36 (challenge II)
- Control group: vehicle
Half of the untreated control animals (group 1) were treated on challenge I and the rest on challenge II with the test material preparations and the vehicle to exclude primary irritation.
- Site: shaved left flank (challenge I) and shaved right flank (challenge II)
- Concentrations: Each animal of the different test groups was challenged with 3 different test material concentrations (i.e. with 1, 3, and 10 %)
- Evaluation (hr after challenge): During the induction phase guinea-pigs were investigated for skin reactions daily, about 24 hours after application of the test material always. After challenge they were examined 24, 48 and 72 hours after administration.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: second challenge

Results 3

Key result

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: second challenge

Results 4

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 5

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

3%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: second challenge

Results 6

Key result

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

3%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 7

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 8

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: second challenge

Results 9

Key result

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

6

Remarks on result:

other: second challenge

Results 10

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 11

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 12

Key result

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

6

Remarks on result:

other: second challenge

Results 13

Group:

positive control

Remarks on result:

not measured/tested

Any other information on results incl. tables

Findings in the induction phase

Due to the test material and the vehicle the skin at the treatment sites showed erythema and/or scales in the induction phase (Groups 2-4).

Findings after first challenge

After the first challenge none of the guinea-pigs of the test material or control groups showed any positive skin reactions.

Findings after second challenge

After the second challenge one of six animals of group 4 (induction with 10% test material) showed positive skin reactions after exposure to all tested concentrations of 1, 3, and 10 % (Table 1).

Table 1: Results of second challenge

Time after challenge (h)	24				48				72
Concentration (g ad 100 mL)	0	1	3	10	0	1	3	10	0	1	3	10
375	0	0	0	0	0	0	0	0	0	0	0	0
376	0	0	0	0	0	+	+	+	0	+	0	+
377	0	0	0	0	0	0	0	0	0	0	0	0
378	0	0	0	0	0	0	0	0	0	0	0	0
379	0	0	0	0	0	0	0	0	0	0	0	0
380	0	0	0	0	0	0	0	0	0	0	0	0

0= negative/ questionable

+ = positive

Clinical findings, body weight and mortality

All the guinea-pigs behaved normally and were without clinical symptoms during the study period. The body weight development was normal and no animal died.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Under the given experimental conditions of the Open Epicutaneous Test according to OECD TG 406 the test substance showed a sensitizing potential.

Executive summary:

A study according OECD TG 406 was conducted to test for skin sensitising properties in guinea-pigs in the Open Epicutaneous Test (OET). A Pretest was performed to determine the threshold concentration after single application with 3, 10 and 30% preparations. The concentrations of 10 and 30% did induce skin irritation. 3% was the maximum feasible non-toxic, non irritant concentration in the preliminary test. Thus the concentrations of 3% and 10% were chosen as concentrations for the sensitisation study.

Four groups with 6 female guinea-pigs, each, were investigated in the sensitisation study:
Group 1 (untreated control) and group 2 (vehicle control: liquid paraffin) were treated to exclude primary irritation.
Group 3 was treated with 0.1 mL of 3 % test material preparation, and Group 4 with 0.1 mL of 10 % test material preparation, during the induction phase.
During this period (21 days of daily treatment) erythema and/or scales were observed on the treated skin in Groups 2-4.
After the first challenge (performed at the left flanks on day 22 of the study) with test material concentrations of 1, 3, and 10 %, none of the different challenge sites in any of the guinea-pigs showed a positive skin reaction.
After the second challenge (on day 36 of the study) with the same concentrations, one of six animals from group 4 showed positive skin reactions after 48 hours to the 1, 3, and 10 % test material preparations.
This animal has to be regarded as sensitised.
Thus under the given experimental conditions the test substance, showed a sensitising potential, even at the maximum non irritant concentration of 3%.