2-heptylcyclopentanone

Endpoint summary

Description of key information

Skin sensitisation (OECDTG406): not sensitising

HRIPT (supporting): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 August, 1980 - 08 October, 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability has been presented as 2 because similar to OECD Guideline protocol has been followed but not GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1981)

Deviations:

yes

Remarks:

no positive control animals to demonstrate the sensitivity and reliability of the test.

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An LLNA skin sensitisation study does not need to be conducted because adequate data from an in vivo GPMT skin sensitisation study is available.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Environmental Safety Division Unilever
- Weight at Start: males: 320-342 g; females: 336-368 g

ENVIRONMENTAL CONDITIONS
No data.

Route:

intradermal

Vehicle:

other: 0.01% Dobs/saline

Concentration / amount:

1%

Day(s)/duration:

Single

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Concentration / amount:

10%

Day(s)/duration:

The patch is held in place for 48 hours. Fourteen days thereafter the animals were challenged.

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

other: ethanol

Remarks:

challenge #1, #2, #3 and #4

Concentration / amount:

1%

Day(s)/duration:

24 and 48 hours

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Test animals: 10 (6 males, 4 females)
Control animals: 8 (4 males, 4 females)

Details on study design:

RANGE FINDING TESTS
- Intradermal injections:
Intradermal injections (0.1 mL/site) were made into the clipped flank of four males at concentrations of 0.1, 0.25, 0.5 and 1% of the test substance in 0.01% Dobs/saline. Twenty-four hours later the reactions were examined for size in millimetres (lenght and breadth), erythema and oedema.

- Epidermal application:
Eight millimetre diameter filter paper patches in 11 mm aluminium patch test cups were saturated with concentrations of 5, 10 and 25% in ethanol and the cups were applied to the shaved flanks of four males and weighing approximately 450 g. The patches were held in place by adhesive plaster wound around the trunk. The patches were removed 24 hours after application and the treatment sites examined 24 and 48 hours after removal of the patches.
The resulting reactions were scored for irritation on a scale from 0 to +++. For shoulder induction, a concentration giving slight but definite irritation was selected. The highest concentration which causes no visible irritation was selected for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
1) Intradermal injections
- Concentration: 1%
- Site: the dorsal scapular region
Three pairs of intradermal injections (0.1 mL/site):
1) Freund's complete adjuvant (FCA) 50:50 with 0.01% Dobs/saline
2) Test substance at 1% in 0.01% Dobs/saline
3) Test substance at 2% in 0.01% Dobs/saline in a 50:50 mixture of FCA with 0.01% Dobs/saline

2) Topical applications one week after the injections:
- Concentration: 10% (in ethanol)
- Amount: saturated patch (control animals: ethanol only)
- Area: 8 cm^2
- Exposure period: 48 hours (occlusive)
- Readings: 24 and 48 hours after patch removal

Controls:
Treated controls: At the same time as the test animals were selected, 4 males were selected as treated controls for the first challenge. They were given a mock induction treatment at the same time and in the same way as for the test animals except that test substance was omitted from the injection and application preparations. At first challenge they were treated in exactly the same way as the test substance.
Untretaed controls: At every challenge in the test 4 previously untreated female or male animals and weighing approximately the same as the test animals at that challenge were treated in exactly the same way as the test animals. When animals of similar weight to the test animals were not available, those as close as possible in weight were selected from stock.

B. CHALLENGE EXPOSURE (control and test group)
- Day of challenge: Fourteen days after application of the induction patch. One week after the first challenge a second challenge was made on the opposite flank exactly as for the first challenge. Further challenges and cross challenges may be made on alternate flanks at weekly or greater intervals as required.
- Concentrations: 10%
- Exposure period: 24 hours (occlusive)
- Sites: clipped and shaved flank
- Amount: saturated patch
- Readings: 24 and 48 hours after patch removal

A reaction was considered to be a sensitization reponse if: response produced scattered, mild erythema (faint pink) or greater and there were no reactions in controls or no reaction greater than barely perceptible erythema in controls.

Positive control substance(s):

no

Key result

Reading:

other: 1st, 2nd, 3rd and 4th reading

Hours after challenge:

24

Group:

other: treated and untreated controls

Dose level:

1%

No. with + reactions:

0

Total no. in group:

8

Key result

Reading:

other: 1st, 2nd, 3rd and 4th reading

Hours after challenge:

48

Group:

other: treated and untreated controls

Dose level:

1%

No. with + reactions:

0

Total no. in group:

8

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

10

Key result

Reading:

other: 2nd and 4th reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

other: 2nd and 4th reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

other: 3rd reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

10

Key result

Reading:

other: 3rd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1%

No. with + reactions:

1

Total no. in group:

10

Irritation in the preliminary study

- As faint pink to pale pink erythema and oedema was observed with 1% in the four animals, this concentration was selected as the intradermal induction concentration.

- At the topical induction of 10% test substance all 4 animals showed barely perceptible erythema 24 hours after treatment. 48 hours after treatment 2 animals showed scattered, mild erythema (faint pink), 1 animal showed barely perceptible erythema and 1 animal showed no effects. For the challenge 1% was determined to be the highest non-irritant concentration.

Interpretation of results:

other: Not a skin sensitizer.

Remarks:

According to Regulation (EC) No 1272/2008 and its updates

Conclusions:

In a guinea pig maximisation test performed equivalent to OECD 406 guideline, the substance is not considered a skin sensitizer.

Executive summary:

The skin sensitisation potential of the substance was investigated by performing a guinea pig maximisation test equivalent to OECD 406 guideline. No reliable positive controles were included. A concentration of 1% was used for the intradermal induction, 10% for the epidermal induction and 1% for the challenge. One animal showed a positive effect (scattered, mild erythema) 48 hours after patch removal in challenge 1 and 3. In challenge 3 in one other animal, a positive effect (scattered, mild erythema) was observed 24 hours after patch removal. This is considered not biologically relevant as one treated control animal also showed a positive effect. In the 8 control animals no positive effects were observed 24 and 48 hours after patch removal. Based on the faint reactions in this study, the substance is not considered a sensitizer.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation:

The skin sensitisation potential of the substance was investigated by performing a guinea pig maximisation test equivalent to OECD 406 guideline. No reliable positive controls were included. A concentration of 1% was used for the intradermal induction, 10% for the epidermal induction and 1% for the challenge. One animal showed a positive effect (scattered, mild erythema) 48 hours after patch removal in challenge 1 and 3. In challenge 3 in one other animal, a positive effect (scattered, mild erythema) was observed 24 hours after patch removal. This is considered not biologically relevant as one treated control animal also showed a positive effect. In the 8 control animals no positive effects were observed 24 and 48 hours after patch removal. Based on the faint reactions in this study, the substance is not considered a sensitizer.

HRIPT:

In a repeated insult patch test, 0.2 mL of 2.5% test substance in Ethanol:DEP (1:3) was applied to the upper back (between the scapulae) and was allowed to remain in direct skin contact for a period of 24 hours. Occluded patches (3.63 cm^2) were applied to the same site on Monday, Wednesday and Friday for a total of 9 applications during the induction period.

Following approximately a 2-week rest period, the challenge patches were applied to previously untreated test sites on the back. After 24 hours, the patches were removed by a CRL technician and the test sites were evaluated for dermal reactions. The test sites were re-evaluated at 48 and 72 hours. The application of 2.5% test substance in Ethanol:DEP (1:3) did not cause irritation or sensitisation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Respiratory sensitisation can be assessed using human data such as indicated in R7.3.5.2 of the ECHA guidance (2015) that indicate respiratory reactions e. g. from consumer experience or occupational exposure. In case no such data are available the respiratory sensitisation can be assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-2, 2015), which says that if the substance is a non skin sensitiser, than it is unlikely to be a respiratory sensitiser.

Justification for classification or non-classification

The substance is negative in the Maximisation skin sensitisation study and therefore classification of this substance for skin and respiratory sensitisation is not warranted according to EU CLP ( (EC) No. 1272/2008 and its updates).