Nonanedioic acid, 1,9-bis(2-octyldodecyl) ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Oct - 14 Nov 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

(1992)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

(2003)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

GROUPE INTERMINISTRIEL DES PRODUITS CHIMIQUES, IVRY-SUR-SEINE, France

Type of study:

Buehler test

Justification for non-LLNA method:

Experience with other fatty acid esters indicates that the LLNA (OECD guideline 429) tends to give false positive results for this group of substances. Therefore, a study according to OECD guideline 406 was performed.

Test material

Test material information

Constituent 1

Reference substance name:

1,9-bis(2-octyldodecyl) nonanedioate

EC Number:

618-295-5

Cas Number:

897626-46-9

Molecular formula:

C49 H96 O4

IUPAC Name:

1,9-bis(2-octyldodecyl) nonanedioate

Details on test material:

- Name of test material (as cited in study report): Nonanedioic acid, 1,9-bis(2-octyldodecyl) ester
- code number: PH-12/0487
- Physical state: yellowish, clear liquid
- Homogeneity: the test item appeared to be homogeneous
- Analytical purity: 96.3 area-% determined by GC-analysis
- Lot/batch No.: CD11150001
- Production date: 25 Apr 2011
- Expiration date of the lot/batch: 23 Mar 2013
- Storage condition of test material: in glass bottle at room temperature
- Date received: 24 Sep 2012

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CHARLES RIVER, L’ARBRESLE, France
- Age at study initiation: 4 weeks
- Weight at study initiation: 229 g-276 g
- Housing: The animals were housed in groups of 2 in polycarbonate containers. The flooring of the cages was covered with dust-free wood shavings and the top fitted a stainless steel lid containing with a feeding device and drinking device of 500 mL.
- Diet: SAFE, 106, ad libitum
- Water: tap water from public distribution system, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Induction 2

Concentration / amount:

Induction: 100%
Challenge: 100%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

paraffin oil

Challenge 2

Concentration / amount:

Induction: 100%
Challenge: 100%

No. of animals per dose:

- 3 (range finding test)
- 20 (test group), 10 (negative control group)

Details on study design:

RANGE FINDING TESTS:
Three guinea pigs were treated with the test item placed onto the selected treatment sites and covered with an occlusive dressing (25mm x 25mm gauze patches hydrophilic Codex of 8-layer Gazin® from Lohmann & Rauscher held in contact with the skin by means of 50 mm wide hypoallergenic micropore™ adhesive tape from 3M and Blenderm™ from 3M) for a period of 6 hours at 4 different concentrations: 100%, diluted at 75% (v/v), 50% (v/v) and 25% (v/v) in liquid paraffin. The animals treated at the concentrations of 100%, 75%, 50% and 25% received 0.5 mL of the corresponding preparation. A macroscopic evaluation of the cutaneous reactions was conducted 24 and 48 hours after removal of the occlusive dressings and rinse with distilled water. The skin reaction was observed and recorded.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 100% test item
- Control group: vehicle
- Site: scapular zone
- Frequency of applications: every 7 days (Days 0, 7, 13)
- Duration: 13 days
- Concentrations: 100% test substance

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: 100% test item (left flank) and patch only (right flank)
- Control group: 100% test item (left flank) and patch only (right flank)
- Site: dorso-lumbar zone, an application on either side of the spine
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48

OTHER:
- After patch removal, the treated areas with the test item at 100% were rinsed with vehicle

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

yes

Remarks:

α-Hexylcinnamaldehyde CAS 101-86-0, the latest 3 tests were carried out on 11 July 2011, 20 Sep 2011, and 22 May 2012

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

induction: 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 100%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

induction: 100%; challenge: 100%

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 100%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

induction: 0%; challenge: 100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 5

Group:

positive control

Remarks on result:

other: no data available

Any other information on results incl. tables

Preliminary study:

24 and 48 hours after removal of the occlusive dressings, no skin reaction was noted with the tested concentrations 100%, 75%, 50% and 25%. In view of these results, the concentration selected was 100% for the 3 inductions of the main study and the concentration selected was 100% for the challenge phase.

Induction phase:

No cutaneous reaction was recorded during the induction phase.

Challenge phase:

No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item at 100%.

No cutaneous intolerance reaction was recorded in animals from the negative control group.

Mortality:

No mortality was registered during the main test.

Body weights:

No abnormalities and no differences in the body weight between the control and the treated group were observed.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified