Isononyl alcohol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Recent, well conducted study acc. to GLP and OECD guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Test material

Test material information

Constituent 1

Reference substance name:

Nonanol N

IUPAC Name:

Nonanol N

Constituent 2

Reference substance name:

Isononyl alcohol

EC Number:

248-471-3

EC Name:

Isononyl alcohol

Cas Number:

27458-94-2

Molecular formula:

C9H20O

IUPAC Name:

3,5,5-trimethylhexan-1-ol

Details on test material:

- Name of test substance: NONANOL N
- Test-substance No.: 07/0724-1
- Batch identification: Nonanol N vom 18.10.2007
- CAS No.: 27458-94-2
- Purity: > 99.9 area-% (analytical report No.: 07L00308)
- Homogeneity: The test substance was homogeneous by visual inspection.
- Storage stability: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

- Test species / strain / quality: Guinea pigs / Dunkin Hartley, Crl:HA
- Reasons for the selection of the test species: The guinea pig has been the animal of choice for predictive sensitization tests for several decades.
- Age on day 0: 5 – 9 weeks
- Sex: Female
- Supplier: Charles River Laboratories, Research Models and Services, Germany GmbH, Stolzenseeweg 32 – 36, 88353 Kisslegg
- Arrival in the testing facility: Acclimatization period (21 days before the first test-substance application)
- Identification: Ear tattoo
- Body weight on day 0: 401 g – 461 g

HOUSING CONDITIONS
- Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 20 – 24°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
- Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
- Type of cage: Plastic cages from Tecniplast Deutschland GmbH (type 3020W009) with perforated base; floor area: 4000 cm²
- Enrichment: Wooden gnawing blocks (Typ NGM E-022); Abedd ® Lab. and Vet. Service GmbH Vienna, Austria
- Number of animals per cage: 5
- Feeding: Kliba Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland ad libitum
- Drinking water: Tap water ad libitum

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Induction 2

Concentration / amount:

undiluted

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Challenge 2

Concentration / amount:

undiluted

No. of animals per dose:

Groups Number of animals
Control group 1 10
Control group 2 10
Test group 20

Details on study design:

RANGE FINDING TESTS
In accordance with the cited Guidelines a slightly irritating concentration should be used in the main test for induction whereas the maximum non-irritant concentration should be applied for challenge.
- Amount applied: 0.5 mL of the test substance / test-substance preparation was applied to each animal.
- Occlusive dressing: 2 x 2 cm gauze patches (6 layers surgical gauze Ph. Eur. from Lohmann GmbH & Co. KG) containing the test substance / test-substance preparation were applied to the skin of the flanks under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 4 cm from Russka), patches of Idealbinde (5 x 5 cm from Pfälzische Verbandstoff-Fabrik) and Fixomull® Stretch (adhesive fleece) from Beiersdorf AG.
- Duration of exposure: 6 hours
- Application site: Right and left flank
- Application frequency: One application
-Number of test animals: 2 per test-substance concentration
-Readings: 1, 24 and 48 h after removal of the patch

MAIN STUDY
- Body weight determination: Individual body weights on day 0 and on the last day of observation (with the exception of the 2nd control group).
- Mortality: Twice each workday (beginning and end) and once on Saturdays, Sundays and on public holidays.

A. INDUCTION EXPOSURE
3 inductions were conducted.
- Amount applied: 0.5 mL of the test substance was applied to each animal.
- Occlusive dressing: 2 x 2 cm gauze patches (6 layers surgical gauze Ph. Eur. from Lohmann GmbH & Co. KG) containing the test substance were applied to the skin of the flank under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 4 cm from Russka), patches of Idealbinde (5 x 5 cm from Pfälzische Verbandstoff-Fabrik) and Fixomull® Stretch (adhesive fleece) from Beiersdorf AG.
- Duration of exposure: 6 hours
- Application site: Intact flank
- Application frequency: Three times at weekly intervals; days 0, 7 and 14 on the same application site
- Readings: 24 h after the removal of the patch
The control groups were not treated, since the test substance was applied undiluted and thus no vehicle was used.


B. CHALLENGE EXPOSURE
The challenge was carried out 14 days after the third induction.
- Amount applied: 0.5 mL of the test substance was applied to each animal. Occlusive dressing: 2 x 2 cm gauze patches (6 layers surgical gauze Ph. Eur. from Lohmann GmbH & Co. KG) containing the test substance were applied to the skin of the flank under an occlusive dressing. The dressing consisted of rubberized linen patches (4 x 4 cm from Russka), patches of Idealbinde (5 x 5 cm from Pfälzische Verbandstoff-Fabrik) and Fixomull® Stretch (adhesive fleece) from Beiersdorf AG.
- Duration of exposure: 6 hours
- Application site: Intact flank
- Readings: 24 and 48 h after the removal of the patch
The test group and control group 1 were treated with the test substance (control group 2 remained untreated).

Positive control substance(s):

not required

Remarks:

However, a separate study is performed twice a year in the laboratory. The positive controls with Alpha-Hexylcinnamaldehyde, techn. 85% showed that the test system was able to detect sensitizing compounds under the laboratory conditions chosen.

Results and discussion

In vivo (non-LLNA)

Results

Group:

test chemical

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Group: test group. No with. + reactions: 0.0. Total no. in groups: 20.0.

Any other information on results incl. tables

CLINICAL OBSERVATIONS AND ASSESSMENT OF FINDINGS

Pretest for selection of epidermal induction and challenge concentration:

The undiluted test substance and a 50% test substance preparation in acetone were tested. After application of both concentrations no skin irritation could be observed.

MAIN STUDY

Induction:

The inductions with the undiluted test substance caused the following skin reactions:

Skin findings	Test group Inductions
	1st	2nd	3rd
Grade 0 Grade 1	20/20 -	20/20 -	15/20 5/20

x/y: number of animals with findings / number of animals tested (reading 24 h after removal of the

patch)

Challenge:

The challenge with the undiluted test substance did not cause any skin reactions neither in animals of the control group 1 nor in test group animals 24 and 48 hours after removal of the patch.

Control group 2 that had been intended for a potential rechallenge, was not treated and therefore not reported.

Body weights:

The expected body weight gain was generally observed in the course of the study.