Dimethoxymethyloctadecylsilane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Aug 2014 – 29 Sep 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2015

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

Type of study:

Buehler test

Justification for non-LLNA method:

The Buehler type of sensitization test was selected since the test substance is a functional silane and the Local Lymph Node Assay as the preferred alternative has shown to provide false positive results for silicone substances.

Test material

Test material information

Constituent 1

Reference substance name:

Dimethoxymethyloctadecylsilane

EC Number:

274-936-5

EC Name:

Dimethoxymethyloctadecylsilane

Cas Number:

70851-50-2

Molecular formula:

C21H46O2Si

IUPAC Name:

dimethoxymethyloctadecylsilane

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 France, L’Arbresle Cedex, France
- Age at study initiation: approximately 4 weeks old
- Housing: in groups of maximum 5 animals per labelled Noryl cage (Tecniplast; 74 cm x 54 cm x 25 cm height) containing sterilised sawdust as bedding material (Lignocel S 8-15, JRS – J. Rettenmaier & Söhne GmbH + CO. KG, Roshenberg, Germany) and shelters (CS3B02A Play tunnels (90 mm x 5 mm x 125 mm), Datesand, Manchester, UK) as cage enrichment.
- Diet: complete maintenance diet for guinea pigs (MS-H, SSNIFF® Spezialdiäten GmbH, Soest, Germany). Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least twice a week.
- Water: tap water, ad libitum
- Acclimation period: at least five 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 (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

- Range finding study: 10, 20, 50 and 100% (v/v)
- Main study: 100% (neat test material)

Challenge

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

- Range finding study: 10, 20, 50 and 100% (v/v)
- Main study: 100% (neat test material)

No. of animals per dose:

4 in the preliminary irritation test
20 in the test group of main study
10 in the negative control goup of the main study

Details on study design:

RANGE FINDING TESTS:

4 animals were used in total in the range finding test. Two different concentrations (2 animals at 10% and 20%; 2 animals at 50% and 100%) were applied (0.5 ml) per animal to the clipped flank using Metalline patches (2x3) mounted on Medical tape, then held in place with Micropore tape and subsequently Coban elastic bandage. After 6 hours, the dressing was removed and the skin cleaned of residual test substance with water. The resulting dermal reactions were assessed for irritation 24 and 48 hours after removal of the last dressing. Based on the results of this preliminary test the following concentrations were chosen for the main test:
- 100% for the dermal inductions
- 100% for the challenge application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 0.5 ml of the neat test substance
- Control group: 0.5 ml of corn oil
- Site: left flank
- Frequency of applications: every 7 days (days 8 and 15 of the study)
- Duration: days 1-15
- Concentrations: 100% (undiluted)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: 0.1 ml of the neat test substance and 0.1 ml of the vehicle
- Control group: 0.1 ml of the neat test substance and 0.1 ml of the vehicle
- Site: posterior right flank (test substance) and anterior right flank (corn oil)
- Concentrations: 100% (undiluted)
- Evaluation (hr after challenge): 24 and 48 h

Animals used in the main sensitisation assessment were weighed on Day 1 of the study and again on termination of the study following completion of the challenge procedures.

All animals were killed following the end of the experimental procedure. No necropsy examination was performed in these animals.

Challenge controls:

The control group is actually a challenge control.

Positive control substance(s):

yes

Remarks:

The recent reliability check was performed in September 2014: Alpha-hexylcinnamicaldehyde undiluted (induction) and 50% in water (challenge)

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:

1

Total no. in group:

20

Clinical observations:

A grade 1 skin reaction was observed in one experimental animal on day 29 in response to the test substance

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Induction: 100%; challenge: 100%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: A grade 1 skin reaction was observed in one experimental animal on day 29 in response to the test substance.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

Induction: 0%; challenge: 100%

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

A grade 1 skin reaction was observed in one control animal on day 29 in response to the test item

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Induction: 0%; challenge: 100%. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: A grade 1 skin reaction was observed in one control animal on day 29 in response to the test item.

Results 3

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 4

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.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

The test item was investigated for skin sensitising potential in a Buehler Test conducted in accordance with OECD TG 406 and in compliance with GLP. The skin reaction observed in response to the undiluted test substance in one (of the twenty) experimental animals in the challenge phase was considered not indicative of sensitisation, based on the presence of a similar response in one of the control animal. Therefore, the test item is concluded to be not sensitising under the conditions of this test.