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Description of key information

The purpose of this study was to determine the sensitising potential of (Chloromethyl)diethoxymethylsilane in the modified local lymph node assay in mice.

The study was performed according to OECD 429. However, an alternative method was used employing the lymph node weight and lymph node cell count to assess proliferation of lymphocytes. In addition, the acute inflammatory skin reaction is measured by ear weight determination of circular biopsies of the ears and ear thickness measurements on test day 1 and test day 4 to identify skin irritation properties of the test item. It is important to determine if a positive test result is due to the skin irritation potential of the test item or due to its sensitising properties.

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 ofα-hexyl cinnamic aldehyde in acetone/olive oil (4:1, v/v)) was employed.

 

Stimulation indices (SI):

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

 

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.

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 test item is classified to be sensitizing to the skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in chemico
Type of information:
other: read-across to LLNA
Adequacy of study:
weight of evidence
Study period:
2019-04-15 until 2019-06-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
In-vivo-study performed due to work safety (external toll production)
Qualifier:
according to
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)
Positive control results:
The reliability control worked as expected (test report)
Key result
Parameter:
other: not applicable
Value:
ca. 0

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on these data, the test item has to be classified as a skin sensitiser (Xi, R43) according to 67/584/EEC and (Cat 1B) according to EC/1272/2008.