4-cyclohexyl-4-methylpentan-2-one

Endpoint summary

Description of key information

The substance is not skin 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:

28.06.1991 - 22.07.1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

May 1981
Reference: B. Magnusson and A. M. Kligman: "The identifieation of contact allergens by animal assay. The guinea pig maximization test" (I Invest. Dermatol., 52, 268-276, 1969) and "Allergie Contact Dermatitis in the Guinea Pig" (Thomas Publishers, Springfield, Illinois, 1970).

Deviations:

yes

Remarks:

no skin reaction after intradermal induction

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The test was done before LLNA as first-choice method for in vivo testing was set into force.

Specific details on test material used for the study:

Test material is a formulation of 10% in white vaseline.

Species:

guinea pig

Strain:

other: Pirbright white Bor:DHPW (SPF)

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: male : 349 - 458 g, female : 305 - 387 g
- Housing: up to maximum 5 animals per cage (Macrolon type IV) with "LIGNOCEL 3/4 Fasern" bedding
- Diet: ad libitum, Ssniff-G pellets
- Water: ad libitum, drinking water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature: 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.

Route:

intradermal

Vehicle:

peanut oil

Concentration / amount:

5%

Day(s)/duration:

Day 0/single injections

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

10%

Day(s)/duration:

Day 7/48 h

Adequacy of induction:

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

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

peanut oil

Concentration / amount:

5%

Day(s)/duration:

Day 21/24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

20 (test group and control)

Details on study design:

RANGE FINDING TESTS:
Intradermal Injection:
- Solvent: water and Freund's complete adjuvant (FCA; Sigma, 8024 Deisenhofen)
- Concentration: 5% of test substance (= a factor 2 dilution of the original 10% formulation in white vaseline)
- Amount animals: 2
- Recordings: 48 h after treatment
- Result: no specific findings

Dermal Application:
- Concentration: 10, 7.5 and 5% of test substance (= undiluted 10% formulation in white vaseline, a factor 1.33 and factor 2 dilution of the original 10% formulation in white vaseline)
- Procedure: closed patch by means of an occlusive bandage
- Amount animals: 2 per concentration
- Recordings: 48 h post application
- Results: 10%: slight erythema; 7,5%: partly slight erythema; 5%: no skin irritation

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2;
1: 3 pairs of intradermal injections: symmetrically in 2 rows an either side of the spine
2: 7 days later: test article was spread in a thick layer which was firmly secured by an occlusive dressing
- Exposure period: 48 h (epicutaneous)
- Site:
1: 4 x 6 cm clipped shoulder region
2: 4 x 5 cm same area
- Test group:
Intradermal:
1 .0.1 mL FCA (diluted w/w in water)
2. 0.1 mL test article diluted in peanut oil (final concentration: 5%, a factor 2 dilution of the original 10% formulation in white vaseline)
3. 0.1 mL test article emulsified in FCA/water (final concentration: 5%, a factor 2 dilution of the original 10% formulation in white vaseline)
Epicutaneous: undiluted test substance (concentration: 10%)
- Control group:
Intradermal:
1 .0.1 mL FCA (diluted w/w in water)
2. 0.1 mL vehicle (undiluted)
3. 0.1 mL vehicle (emulsified w/w with FCA)
Epicutaneous: vehicle

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 14 days after second stage induction
- Site: 5 x 5 cm on each flank, sealed for 24 h under an occlusive dressing
- Concentrations: maximal non-irritating concentration to the left flank and the vehicle to the right flank
- Evaluation (hr after challenge): 24 and 48 hours


SCORING SYSTEM:
0: No reaction
1: Scattered mild redness
2: Moderate and diffuse redness
3: Intense redness and swelling

Positive control substance(s):

yes

Remarks:

2,4-dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer)

Positive control results:

The reaction to the positive contml substances 2,4-dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) is tested periodically. The last test with an acceptable level of response to each of these substances was performed in April, 1991.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction intradermal: 0%; Challenge: 5%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Induction intradermal: 0%; challenge: 5%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

Induction intradermal: 5%; challenge: 5%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

Induction intradermal: 5%; challenge: 5%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: CLP criteria not met

Conclusions:

No animal showed an allergic response, the test article is not sensitising.

Executive summary:

The aim of the current study was to assess the contact sensitizing potential of the test item, according to the OECD test guideline 406 with particular reference to the publications by B. Magnusson and A. M. Kligman (1969 and 1970).

 

The potential skin sensitizing properties were assessed in the guinea pig maximization test using 20 test and 20 control animals. Following induction exposure to the test article or the vehicle, the animals were subjected two weeks later to a challenge exposure with the test article. Allergic responses to the challenge procedure were evaluated 24 and 48 hours after the end of the exposure period.

In the range finding study no specific findings were observed after intradermal injection of 50% test material (actual concentration of test substance 5%). After dermal application of 100% (actual concentration 10% in white vaseline) of the test item slight erythema was observed, while a concentration of 50% (actual concentration 5%) did not show any signs of skin irritation. These were the tested concentrations in the main study (intradermal induction: 5%, epicutaneous induction: 10%; epicutaneous challenge: 5%). In the main study the sensitization rate at 24 h and 48 h after challenge was 0%. At day 17 p.a. one guinea pig of the test group died, however, this was due to a disease of the respiratory tract and independent of the treatment.

According to the CLP Regulation (EC) No 1272/2008 the sub-categories for a skin sensitiser are as follows:

Sub-category 1A: Substances showing a high frequency of occurrence in humans and/or a high potency in animals can be presumed to have the potential to produce significant sensitisation in humans. Severity of reaction may also be considered. The obtained data from the maximsation animal test can be used in the classification for sub-category 1A (Table 3.4.3): >= 30% responding at =< 0.1% intradermal induction dose or >= 60% responding at > 0.1% to =< 1% intradermal induction dose

Sub-category 1B: Substances showing a low to moderate frequency of occurrence in humans and/or a low to moderate potency in animals can be presumed to have the potential to produce sensitisation in humans. Severity of reaction may also be considered. The obtained data from the maximisation animal test can be used in the classification for sub-category 1B (Table 3.4.4): >= 30% to <60% responding at > 0.1% to =< 1% intradermal induction dose or >= 30% responding at > 1% intradermal induction dose

Since no animal showed an allergic response, the test article does not have to be classified as sensitising.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

For this endpoint there is one study available in which the contact sensitizing potential of the test item was assessed according to the OECD test guideline 406 in a guinea pig maximization test using 20 test and 20 control animals. Following two induction stages (intradermal and epicutaneous), the animals were subjected two weeks later to a challenge and allergic responses were evaluated 24 and 48 hours later. The test item is a formulation of 10% test substance in white vaseline.

 

In the range finding study no specific findings were observed after intradermal injection of 50% of the test item (actual concentration of test substance 5%). After dermal application of 100% (actual concentration 10%) of the test item slight erythema was observed, while a concentration of 50% (actual concentration 5%) did not show any signs of skin irritation. These were the tested concentrations in the main study (intradermal induction: 5%, epicutaneous induction: 10%; epicutaneous challenge: 5%). Peanut oil was used as vehicle. In the main study the sensitization rate at 24 h and 48 h after challenge was 0%. At day 17 p.a. one guinea pig of the test group died, however, this was due to a disease of the respiratory tract and independent of the treatment.

 

Since no animal showed an allergic response, the test substance does not have to be classified as sensitising.

Justification for classification or non-classification

According to the CLP Regulation (EC) No 1272/2008 the sub-categories for a skin sensitiser are as follows:

Sub-category 1A: Substances showing a high frequency of occurrence in humans and/or a high potency in animals can be presumed to have the potential to produce significant sensitisation in humans. Severity of reaction may also be considered. The obtained data from the maximisation animal test can be used in the classification for sub-category 1A (Table 3.4.3): >= 30% responding at =< 0.1% intradermal induction dose or >=60% responding at > 0.1% to =< 1% intradermal induction dose

Sub-category 1B: Substances showing a low to moderate frequency of occurrence in humans and/or a low to moderate potency in animals can be presumed to have the potential to produce sensitisation in humans. Severity of reaction may also be considered. The obtained data from the maximisation animal test can be used in the classification for sub-category 1B (Table 3.4.4): >= 30% to <60% responding at > 0.1% to =< 1% intradermal induction dose or >= 30% responding at > 1% intradermal induction dose.

The test substance does not have to be classified as sensitising.