(chloromethyl)diethoxymethylsilane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019-04-15 until 2019-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2010

Deviations:

no

GLP compliance:

yes

Remarks:

Freie und Hansestadt Hamburg, Behörde für Gesundheit und Verbraucherschutz, 20539 Hamburg, Germany

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

(chloromethyl)diethoxymethylsilane

EC Number:

218-657-9

EC Name:

(chloromethyl)diethoxymethylsilane

Cas Number:

2212-10-4

Molecular formula:

C6H15ClO2Si

IUPAC Name:

(2-chloro-1,1-diethoxyethyl)silane

Test material form:

liquid

Details on test material:

Purity approx. 99% (GC)

In vivo test system

Test animals

Species:

mouse

Strain:

NMRI

Remarks:

NMRI / Crl:NMRI

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Weight at study initiation: 25-35 g
- Housing: semi-barrier in an air-conditioned room
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: adequate


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3 °C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 12 h dark, 12 h light

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

50, 75 and 100 %

No. of animals per dose:

six

Details on study design:

Stimulation indices were calculated for the lymph node cell count, lymph node weight, ear weight and ear thickness by dividing the average values per group of the test item treated animals by the vehicle treated ones.
Values above 1.4 (lymph node cell count to identify sensitisation) or 1.1 (ear weight to identify irritation) are considered positive (these values were fixed empirically during the interlaboratory validation of this method (Ehling et al. 2005a and 2005b)).
Two concentrations of (Chloromethyl)diethoxymethylsilane (50% and 75%), dissolved in acetone/olive oil (4:1, v/v) (w/w) and the undiluted test item (100%) were tested in six female NMRI mice per group and compared to a vehicle control group.
Acetone/olive oil (4:1, v/v) was selected as recommended by the OECD guideline and it provided a most suitable solution of the test item both for administration and adherence to the mouse ear of such high concentrations. It was also used as negative reference item.
In addition, a positive control group (20% solution v/v of α-hexyl cinnamic aldehyde in acetone/olive oil (4:1, v/v)) was employed.
In the main study treatment with the test item at the concentration of 50% did not reveal any statistical significantly increased values for the lymph node cell count and lymph node weight. The stimulation indices of the lymph node cell count did not exceed the threshold level of 1.4.
The threshold level for the ear weight of 1.1. was not exceeded and no increase of the ear thickness was observed, i.e. no irritating properties were noted.
Administrations of 75% of undiluted test item led to an increase (significant at p <= 0.05) of the stimulation index of the lymph node cell count above the threshold level of 1.4 indicating sensitizing properties. No increase was noted in the stimulation index of the ear weight at a concentration of 75% and for the undiluted test item, in addition, the respective indices did not exceed the threshold level of 1.1, i.e. no overall irritating potential was noted.
The positive control group caused the expected increases in lymph node cell count and lymph node weight (significant at p <=0.01). Therefore, the study can be regarded as valid. No signs of systemic intolerance were recorded.

Positive control substance(s):

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

Results and discussion

Positive control results:

The reliability control worked as expected (test report)

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Remarks:

based on lymph node cell count

Value:

1.412

Test group / Remarks:

75%

Results 2

Key result

Parameter:

SI

Value:

1.543

Test group / Remarks:

100%

Results 3

Key result

Parameter:

SI

Value:

1.242

Test group / Remarks:

25%

Any other information on results incl. tables

Parameter	Group 1 negative control	Group 2, 50%	Group 3, 75%	Group 4, 100%	Group 5, positive control
Lymph node cell count	1.000	1.242	1.412	1.543	1.451**
Lymph node weight	1.000	1.104	1.313	1.417**	1.708**
Ear weight	1.000	1.000	0.989	0.946	1.065
Ear thick-ness, TD4	1.000	1.000	0.976	0.984	1.107

** significantly different from control at P<= 0.01

Applicant's summary and conclusion

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

The substance is sensitizing to the skin.

Executive summary:

In conclusion, under the present test conditions, (chloromethyl)diethoxymethylsilane at the concentration of 50% (w/w) in acetone/olive oil (4.1, v/v) did not reveal any skin sensitizing properties in the local lymph node assay. The 75% concentration and the undiluted test item reveled signs of skin sensitization but no irritating potential, and therefore the teste item is classified to be sensitizing to the skin.