3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]propane-1,2-diol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 October, 2014 - 20 October, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2010)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

(2003)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Food and Agricultural Materials Inspection Centre (FAMIC), 12 Nousan, Notification No 8147, April 2011, including the most recent partial revisions.

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:

3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]propane-1,2-diol

EC Number:

807-413-2

Cas Number:

70280-68-1

Molecular formula:

C13H34O5Si3

IUPAC Name:

3-[3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy]propane-1,2-diol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): X-22-1927
- Appearance: Clear light yellow liquid
- CAS Number: 70280-68-1

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: 20 - 24 g
- Housing: Animals were group housed in labeled makrolon cages.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

0, 25, 50 and 100%

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
Two test substance concentrations were tested; a 50% and 100% concentration. The highest concentration was the maximum concentration as required in the test guidelines.
The test system, procedures and techniques were identical to those used in the main study except that the assessment of lymph node proliferation and necropsy were not performed. Two young adult animals per concentration were selected. Each animal was treated with one concentration on three consecutive days. Animals were group housed in labeled Makrolon cages (MII type, height 14 cm). Ear thickness measurements were conducted using a digital thickness gauge (Kroeplin C110T-K) prior to dosing on Days 1 and 3, and on Day 6.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: DPM values are presented for each animal and for each dose group. A Stimulation Index (SI) is calculated for each group using the individual SI values. The individual SI is the ratio of the DPM/animal compared to DPM/vehicle control group.
If the results indicate a SI ≥ 3, the test substance may be regarded as a skin sensitizer.

ANIMAL ASSIGNMENT
Three groups of five animals were treated with one test substance concentration per group. One group of five animals was treated with vehicle.

TREATMENT PREPARATION AND ADMINISTRATION:
Test substance preparation: The test substance formulations (w/w) were prepared within 4 hours prior to each dosing. No adjustment was made for specific gravity of the vehicle. Homogeneity was obtained to visually acceptable levels.
Rationale for vehicle: The vehicle was selected on the basis of maximizing the solubility using the test substance data provided by the sponsor and trial formulation results performed at WIL Research Europe.

Induction - Days 1, 2 and 3; Excision of nodes - Day 6; Tissue processing for radioacitivity - Day 6; Radioactivity measurements - Day 7; Performed according to test guidelines.

Observations:
Mortality/Viability: Twice daily.
Body weights: On Day 1 (pre-dose) and Day 6 (prior to necropsy).
Clinical signs: Once daily on Days 1-6 (on Days 1-3 between 3 and 4 hours after dosing).
Irritation: Once daily on Days 1-6 (on Days 1-3 within 1 hour after dosing) according to the following numerical scoring system. Furthermore, a description of all other (local) effects was recorded.

Necropsy: No necropsy for gross macroscopic examination was performed according to protocol.

Positive control substance(s):

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

Statistics:

Not performed.

Results and discussion

Positive control results:

The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe B.V. is an appropriate model for testing for contact hypersensitivity. See attached document 'Reliability check'.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The SI values calculated for the substance concentrations 25, 50 and 100% were 3.1, 4.5 and 8.1, respectively.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Mean DPM/animal values for the experimental groups treated with test substance concentrations 25, 50 and 100% were 1725, 2463 and 4468 DPM, respectively. The mean DPM/animal value for the vehicle control group was 549 DPM.

Any other information on results incl. tables

Results Pre-screen test:

No irritation and no signs of systemic toxicity were observed in any of the animals examined.

Variations in ear thickness during the observation period were less than 25% from Day 1 pre-dose values.

Based on these results, the highest test substance concentration selected for the main study was a 100% concentration.

Other results - main study:

No irritation of the ears was observed in any of the animals examined.

 

The majority of auricular lymph nodes were considered normal in size, except for the node(s) of three animals treated at 100% which appeared larger in size as compared to the other groups.

No macroscopic abnormalities of the surrounding area were noted for any of the animals.

 

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an LLNA skin sensitisation study, performed according to OECD 429 test guideline and GLP principles, X-22-1927 was considered to be a skin sensitiser, as the SI appeared to be ≥ 3 when tested up to and including 100%.

Executive summary:

X-22-1927 was tested in an LLNA skin sensitisation study, performed according to OECD 429 test guideline and GLP principles.

No irritation of the ears was observed in any of the animals examined. The majority of auricular lymph nodes were considered normal in size, except for the node(s) of three animals treated at 100% which appeared larger in size as compared to the other groups.

No macroscopic abnormalities of the surrounding area were noted for any of the animals. The SI values calculated for the substance concentrations 25, 50 and 100% were 3.1, 4.5 and 8.1, respectively. These results show that the test substance elicits a SI≥3. The EC3 value (the estimated test substance concentration that will give a SI =3) was established to be between 0 and 25%. Since the mean SI value (3.1) of the group treated at 25% was close to 3 the EC3 value was considered to be approximately 25%. Based on the results, X-22-1927 should be classified as skin sensitisation (Category 1B) and labeled with H317: May cause an allergic skin reaction according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.