Registration Dossier

Administrative data

Description of key information

Skin sensitisation (OECD 406): not sensitizing

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
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted
17 July 1992
GLP compliance:
yes (incl. certificate)
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
Remarks:
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
Remarks:
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 group
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 group
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 group
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 group
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
Remarks:
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:

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 atopical 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).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the results in this study methyl nonyl ketone 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).