1-Propanethiol, 3-(trimethoxysilyl)-, adduct with 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane (1:1)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-05-20 to 2009-05-26

Reliability:

1 (reliable without restriction)

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

not applicable

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:

3,3,12,12-tetramethoxy-2,13-dioxa-7,8-dithia-3,12-disilatetradecane; 5-(7,7-dimethoxy-2-oxo-8-oxa-3-thia-1-aza-7-silanonan-1-yl)-1-[(7,7-dimethoxy-2-oxo-8-oxa-3-thia-1-aza-7-silanonan-1-yl)methyl]-1,3,3-trimethylcyclohexane; [3-({[(3-isocyanato-3,5,5-trimethylcyclohexyl)methyl]carbamoyl}sulfanyl)propyl]trimethoxysilane; [3-({[(5-isocyanato-1,3,3-trimethylcyclohexyl)methyl]carbamoyl}sulfanyl)propyl]trimethoxysilane

EC Number:

700-534-0

Cas Number:

117172-56-2

Molecular formula:

Not applicable: UVCB substance, see section 1.2 and 1.4. The UVCB substance consits of differnt products consiting of differnt isomers: Product I and Product II cannot analytically be distinguished and moreover, Product I-III are expected to consist of isomers that can neither analytically be identified nor quantified.

IUPAC Name:

3,3,12,12-tetramethoxy-2,13-dioxa-7,8-dithia-3,12-disilatetradecane; 5-(7,7-dimethoxy-2-oxo-8-oxa-3-thia-1-aza-7-silanonan-1-yl)-1-[(7,7-dimethoxy-2-oxo-8-oxa-3-thia-1-aza-7-silanonan-1-yl)methyl]-1,3,3-trimethylcyclohexane; [3-({[(3-isocyanato-3,5,5-trimethylcyclohexyl)methyl]carbamoyl}sulfanyl)propyl]trimethoxysilane; [3-({[(5-isocyanato-1,3,3-trimethylcyclohexyl)methyl]carbamoyl}sulfanyl)propyl]trimethoxysilane

Constituent 2

Reference substance name:

Reaction products of 3- (trimethoxysilyl)propane-1-thiol and 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane (1:1)

IUPAC Name:

Reaction products of 3- (trimethoxysilyl)propane-1-thiol and 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethylcyclohexane (1:1)

Details on test material:

- Name of test material: Intermediate 36
- Colour: light yellow
- Physical state: liquid
- Analytical purity: >99%

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

10; 25; 50; 100 ( % w/v) (25 µL)

No. of animals per dose:

4 animals/treatment group

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Stimulation index values of Intermediate 36 were 55.4, 91.5, 91.8, and 76.6 at treatment concentrations of 100, 50 %, 25 % and 10 %, respectively. A stimulation index of 3 or greater is an indication of a positive result.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

DPM was measured for each pooled group of nodes. The measured DPM values were corrected with the background DPM value (“DPM”). The average of the two measured DPM values of 5 (w/v) % TCA solutions was used as the background DPM value. The results were expressed as “DPN” (DPM divided by the number of lymph nodes) following the industry standard for data presentation. Stimulation index (SI = DPN value of a treated group divided by the DPN value of the negative control group) for each treatment group was also calculated. The DPM for the experimental groups treated with the test substance concentrations 10, 25, 50 and 100 (w/v)% were 68518, 82042, 81768 and 49553, respectively. The DMP for the vehicle control group was 894.

Any other information on results incl. tables

Interpretation of results

The test item is regarded as a sensitiser if both of the following criteria are fulfilled:

- That exposure to at least one concentration of the test item resulted in an incorporation of 3HTdR at least 3-fold or greater than recorded in control mice, as indicated by the stimulation index.

- The data are compatible with a conventional dose response, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

Applicant's summary and conclusion

Interpretation of results:

sensitising

Remarks:

Migrated information

Conclusions:

In conclusion, under the conditions of the present assay Intermediate 36, tested in a suitable vehicle, was shown to have a strong sensitisation potential (sensitiser) in the Local Lymph Node Assay.

Executive summary:

Local Lymph Node Assay according to OECD 429 and Commission Regulation (EC) No 440/2008 of 30 May 2008, B.42 was performed with CBA/J@Rj mice. The aim of this study was to determine the skin sensitisation potential of Intermediate 36 following dermal exposure in the Local Lymph Node Assay. The test item was a light yellow liquid; vehicle compatibility was verified in a

Preliminary Compatibility Test with Acetone: Olive oil 4:1 mixture (AOO). The maximum available concentration was 100% in this vehicle. A Preliminary Irritation/Toxicity test was performed with the test item at concentrations of 100 % and 50 % in the selected vehicle. The applicability and biocompatibility of the test item on the ears of animals at the maximum concentration of test item of 100 % was acceptable. In the main assay twenty female CBA/J@Rj mice were allocated to 6 groups / 4 animals each:

- 3 groups received the appropriate formulation of Intermediate 36 at concentrations of 100 %, 50 %, 25 % and 10 %,

- the negative control group received the vehicle (AOO),

- the positive control group received 25 (w/v) % HCA in AOO

The test item solutions were applied on the dorsal surface of ears of experimental animals (25 l/ear) for three consecutive days (Days 1, 2 and 3). There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by incorporation of tritiated methyl thymidine (3HTdR) and the values obtained were used to calculate stimulation indices (SI).

No mortality or systemic clinical signs were observed during the study. No treatment related effect on the body weights was observed. Erythema and coated fur were observed in the 100 %, 50 % and 25% treated groups, erythema was observed at the 10 % treated group. Stimulation index values of the test item were 55.4, 91.5, 91.8, and 76.6 at treatment concentrations of 100, 50 %, 25 % and 10 %, respectively. α-Hexylcinnamaldehyde (25 (w/v) % dissolved in AOO) was used as a positive control to demonstrate the appropriate performance of the assay. A significant lymphoproliferative response (stimulation index value of 10.1) was noted for the positive control chemical and this result confirmed the validity of the assay.

In conclusion, under the conditions of the present assay Intermediate 36, tested in a suitable vehicle, was shown to have a strong sensitisation potential (sensitiser) in the Local Lymph Node Assay.