Oxacycloheptadecan-2-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 August 2009 - 08 September 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

24 April 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

Commission Regulation No. 440/2008

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Pentadecan-15-olide

EC Number:

203-354-6

EC Name:

Pentadecan-15-olide

Cas Number:

106-02-5

Molecular formula:

C15H28O2

IUPAC Name:

oxacyclohexadecan-2-one

Test material form:

solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: soluble in acetone/olive oil 4:1

In vivo test system

Test animals

Species:

mouse

Strain:

CBA/Ca

Remarks:

(CBA/CaOlaHsd)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-23 g
- Housing: individuall in suspended solid-floor polypropylene cages furnished with softwood woodflakes
- Diet (e.g. ad libitum): 2014 Teklad Global Rodent diet, Harlan Teklad, Blackthorn, Bicester, Oxon, UK, ad libitum
- Water (e.g. ad libitum): mains tap water, ad libitum
- Acclimation period: at least 5 days
- Indication of any skin lesions: none

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 (target)
- Humidity (%): 30-70 (target)
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12
- IN-LIFE DATES: From: 26 August 2009 To: 8 September 2009

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

50% w/w in the prelimianry study
50%, 25% and 10% w/w in the main study

No. of animals per dose:

Preminary study: 1
Main study: 4 females/dose

Details on study design:

PRE-SCREEN TESTS:
- Irritation: no excessive local irritation
- Systemic toxicity: there were no signs of systemic toxicity during 6 days post-administration

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: The proliferation response of lymph node cells was expressed as the number of radioactive disintegrations per minute per lymph node and as the ratio of 3HTdR incorporation into lymph node cells of test nodes relative to that recorded for the control nodes (Stimulation Index).
The test material is regarded as a sensitizer if at least one concentration of the test material results in a threefold or greater increase in 3HTdR incorporation compared to control values. Any test material feiling to produce a threefold or greater increase in 3HTdR incorporation will be classified as a non-sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION: The test mateial was freshly prepared as a solution in acetone/olive oil 4:1. The mice were treated by daily application of 25 µL of the test material at a concentration of 50%, 25% and 10% of the test material to the dorsal surface of each ear for three consecutive days. The test material forulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
A further group of four mice received the vehicle alone in the same manner.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Not applied.

Results and discussion

Positive control results:

Hexyl cinamic aldehyde produced SI of 8.34 at 15% (v/v) in acetone/olive oil (project number 0039/1080, study dates 24 April 2009-30 April 2009).

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

1.34

Test group / Remarks:

10% cyclohexadecanone

Results 2

Key result

Parameter:

SI

Value:

1.92

Test group / Remarks:

25% cyclohexadecanone

Results 3

Key result

Parameter:

SI

Value:

2.56

Test group / Remarks:

50%

Cellular proliferation data / Observations:

CELLULAR PROLIFERATION DATA:
DPM:
Vehicle 15727.81
10% cyclohexadecanone: 20996.87
25% cyclohexadecanone: 30196.62
50% cyclohexadecanone: 40312.02

DETAILS ON STIMULATION INDEX CALCULATION
DPM/Node:
Vehicle: 1965.98
10% cyclohexadecanone: 2624.61
25% cyclohexadecanone: 3774.58
50% cyclohexadecanone: 5039.00

CLINICAL OBSERVATIONS:
There were no clinical signs noted.

BODY WEIGHTS
There were no mortalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the reliable OECD 429 guideline study performed with 50%, 25% and 10% test substance in acetone/olive oil (4:1 v/v), oxacyclohexadecan-2-one is not sensitizing to skin.

Executive summary:

In the GLP-compliant OECD 429 guideline study, oxacyclohexadecan-2 -one at concentrations 10%, 25% and 50% was found to be not sensitizing to skin . The Stimulation Indices were 1.34, 1.92 and 2.56 for 10%, 25% and 50% solutions, respectively. No mortalities occurred and no clinical signs were noted. The potisive control hexyl cinnamic aldehyde produced a Stimulation Index 8.34 at 15% in acetone/olive oil (4:1 v/v). Based on these results, classification of oxacyclohexadecan-2-one for skin sensitization is not warranted.