undecan-2-one; methyl nonyl ketone

Endpoint summary

Description of key information

Skin Sensitization:

Based on the results in this study the compound does not need to be classified as a skin sensitizer in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

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:

09-March-2002 to 11-July-2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from study report

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted
17 July 1992

GLP compliance:

yes

Remarks:

(incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Existing GPMT study of good quality that was generated before 11 October 2016.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch No.of test material: 05500109421007
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperatt,rre in the dark
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: test material was used as supplied
OTHER SPECIFICS: clear colourless liquid

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK and Harlan UK Limited, Bicester, Oxon, UK. (The animals used in the topical induction sighting study were obtained from Harlan UK Limited and those for the remainder of the study were from David Hall Limited)
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 300 to 450g,
- Housing: oused singly or in pairs in solid-floor polypropylene cages furnished with woodflakes. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Diet: ad libitum, Certified Guinea Pig Diet (Code 5026) supplied by PMI Nutrition International, Nottingham, UK
- Water: ad libitum
- Acclimation period: acclimatisation period of at least five days
- Indication of any skin lesions:
ENVIRONMENTAL CONDITIONS
- Temperature (°C):17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Route:

intradermal

Vehicle:

arachis oil

Concentration / amount:

1% (v/v)

Day(s)/duration:

1 injection, with evaluation after 24 and 48 hours

Adequacy of induction:

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

Route:

intradermal

Vehicle:

other: Freund's Complete Adjuvant 1:1 Distilled water

Concentration / amount:

1% (v/v)

Day(s)/duration:

1 injection, with evaluation after 24 and 48 hours

Adequacy of induction:

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

Route:

intradermal

Vehicle:

other: Freund's Complete Adjuvant 1:1 diluted with Distilled water

Concentration / amount:

0%

Day(s)/duration:

1 injection, with evaluation after 24 and 48 hours

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Undiluted
Loaded WHATMAN No. 4 dressing, 40 mm x 20 mm

Day(s)/duration:

Exposure for 48 h (7 days after intradermal induction)

Adequacy of induction:

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

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

arachis oil

Concentration / amount:

100% and 75% (v/v)

Day(s)/duration:

24 h

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 (Each animal was exposed to the substance 100% on one flank and 75% (v/v) on the other)

Details on study design:

RANGE FINDING TESTS:

Range for Intradermal induction:
- Exposure period: 1 Injection
- Number of animals: 2
- Site: Shoulder (clipped)
- Observation period: 24/48/72 h and 7 Days
- Concentrations: 1% and 5% (v/v) in Arachis Oil

Range for Topical induction:
- Exposure period: 48 h (occusive)
- Number of animals: 2
- Site: flank (clipped)
- Observation period: 1/24/48 h after dressing removal
- Concentrations: 75%, 50% arid 25% v/v in arachis oil BP

Range for Topical challenge:
- Exposure period: 24 h (occusive)
- Number of animals: 2 (Animals were treated identically to the control animals of the main study)
- Site: flank (clipped)
- Observation period: 1/24/48 h after dressing removal
- Concentrations: 75%, 50% arid 25% v/v in arachis oil BP

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal, 1 epicutaneous

Intradermal
- Exposure period: 1 injection
- Test group: 1
- Control group: 1
- Site: shoulder
- Frequency of applications: once
- Observation period: 24/48 h
- Concentrations:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1: 1
b) a 1 % v/v formulation of the test material in arachis oil BP
c) a 1 % v/v formulation of the test material in a 1: 1 preparation of Freund's Complete Adjuvant plus distilled water epicutaneous
- Exposure period: 48 hours (7 days after intradermal induction)
- Test groups: 1
- Control group: 1
- Site: shoulder
- Observation period: 24 h after removal of the patch
- Frequency of applications: once
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: 1
- Control group: 1
- Site: flank (Shorn)
- Observation period: 24/48 h after removal of the patch
- Concentrations: 100% and 75%
- Evaluation (hr after challenge):

OTHER: The challenge sites were swabbed with cotton wool soaked in diethyl ether to remove residual material. The position of the treatment sites was identified by using a black indelible marker-pen.

Challenge controls:

The procedure was identical to that used for the test animals except that the test material was omitted.

Positive control substance(s):

yes

Remarks:

Historical control data: 2-Mercaptobenzothiazole and alpha-Hexylcinnamaldehyde

Positive control results:

Historical data:
- 2-Mercaptobenzothiazole: 100% sensitisation
- alpha-Hexylcinnamaldehyde: 20-50% sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

75% (v/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

75% (v/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% (v/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% (v/v)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Neg.Control

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

Neg. Control

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

other: Not classified Annex I of the CLP Regulation (1272/2008/EC)

Conclusions:

Based on the results in this study the compound does not need to be classified as a skin sensitizer in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

The study was performed to assess the contact sensitisation potential of Methyl Nonyl Ketone in the albino guinea pig. The method was designed to meet the requirements of OECD guideline No. 406, and was performed under GLP. Ten test and five control animals were used for the study. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as: 1 % v/v in arachis oil BP for intradermal induction, undiluted for topical induction, undiluted as supplied and 75% v/v in arachis oil BP for topical challenge. Under the conditions of the test, the test material produced a 0% sensitisation rate.The test material therefore does not need to be classified as a skin sensitizer in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin Sensitization:

1. The study was performed to assess the contact sensitisation potential of Methyl Nonyl Ketone in the albino guinea pig. The method was designed to meet the requirements of OECD guideline No. 406, and was performed under GLP. Ten test and five control animals were used for the study. Two phases were involved in the main study; an induction of a response by intradermal injection and topical application and a topical challenge of that response. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as: 1 % v/v in arachis oil BP for intradermal induction, undiluted for topical induction, undiluted as supplied and 75% v/v in arachis oil BP for topical challenge. Under the conditions of the test, the test material produced a 0% sensitisation rate.The test material therefore does not need to be classified as a skin sensitizer in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

2. Magnusson & Kligman test was carried out to assess the dermal sensitization potential of methyl nonyl ketone (CAS: 112 -12 -9) in guinea pigs. 10 Hartley guinea pigs/sex were used for the main study and a group of 5 guinea pigs served as controls. The concentrations used for the main study were determined in a pre screening test.For intradermal induction: 0.1 ml/injection site using concentrations of 1% and 5% v/v in arachis oil BP. The highest concentration that caused only mild to moderate skin irritation, well tolerated systemically was selected. Topical induction: 2 guinea pigs were treated with the undiluted test material and 3 preparations of the test material (75%; 50%; 25% in arachis oil BP). Application was made to the clipped flanks under occlusive dressing for 48h. The highest concentration that caused only mild to moderate dermal irritation was selected. Topical challenge: the undiluted test material and 3 preparations (75%, 50% and 25% in arachis oil BP) were applied under occlusive dressing for 24 h. the highest non-irritant concentration and one lower concentration were selected for the topical challenge stage of the main study.In the main study, on day 0 3 injections of 0.1 ml were injected on the test site, a) Freund complete adjuvant plus distilled water (1/1) b) a 1% v/v formulation of the test material in arachis oil BP and c) a 1% v/v formulation of test material in a 1/1 preparation of Freund’s complete adjuvant plus water. Then on day 7 undiluted test chemical was applied topically to guinea pig skin for 48 hours. After a suitable rest period, challenge exposure was performed, where the guinea pigs were challenged with 75%v/v of the test chemical in arachais oil BP for 48 hours. The test sites were observed for signs of dermal sensitization after the challenge exposure.0% sensitization rate was recorded in the guinea pigs after the challenge exposure. Hence, methyl nonyl ketone was considered to be not a skin sensitizer.

3. A human maximization test was carried out to assess the dermal sensitization potential of methyl nonyl ketone (CAS no.: 112 -12 -9). Methyl nonyl ketone 5% in petrolatum was applied to the skin of 25 human volunteers and observed for signs of dermal sensitization (duration of exposure, observation period not specified).Methyl nonyl ketone 5% in petrolatum did not induce any sensitization reactions on the skin of 25 human volunteers. Hence, methyl nonyl ketone was considered to be not sensitizing to skin.

4. Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration (ICC) and application challenge concentration (ACC)] of Methyl nonyl ketone (CAS no.: 112 -12 -9). Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization study and 4 previously untreated animals of the same sex were used as challenge controls. The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ]. The ICC and ACC for methyl nonyl ketone was determined to be 0.5% and 10% respectively. In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included. At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls. No signs of contact sensitization were observed at 0. 5% ICC and 10% ACC concentrations. Hence, methyl nonyl ketone was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

5. Modified Draize Technique was employed to determine the concentrations suitable\ for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of the read across chemical Octan-2 -one (CAS no.: 111 -13 -7). Hartley strain albino guinea pigs bred were used for the study. Four guinea pigs of same sex were used for the preliminary irritation study and 10 guinea pigs were used for the main sensitization studyand 4 previously untreated animals of the same sex were used as challenge controls.The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC) ].The ICC and ACC for the test chemical was determined to be 1% and 20% respectively.In the induction phase, 0.1 ml aliquots of test substance at 2.5 times the ICC were injected intradermally at 4 sites which overlie the 2 auxillary and 2 inguinal lymph nodes. After a rest period of 14 days, each animal was challengedintradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC: the topical application was made by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered. Twenty-four hours later the reactions were scored and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.At each challenge with controls, 4 previously untreated animals of the same sex were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale and individual reactions were considered positive if (a) they were + or greater and (b) there were no erythema reactions in controls. No signs of contact sensitization were observed at 1% ICC and 20% ACC concentrations. Hence, the test chemical was considered to be non-sensitizing to the skin of albino Hartley guinea pigs.

6. Maximization test was carried out to find skin sensitization of the read across substance Acetate C-8 (CAS no.: 112 -14 -1). The test was carried out on 24 volunteers. The material Acetate C-8 was tested at a concentration of 8% in petrolatum, no sensitization reaction was observed. Therefore,the substance Acetate C-8 can be considered as non-sensitizing to human.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of the target substance it can be concluded that the test substance Methyl nonyl ketone (CAS no.: 112 -12 -9) was non-sensitizing to the skin and can be considered as non-sensitizing substance according to the CLP criteria.