Silane, triethyl[[4-(triethylsilyl)-3-butyn-1-yl]oxy]-

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 June 2014 to 14 July 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted following OECD/EU guideline "Principles on Good Laboratory Practice (GLP) (as revised in 1997), ENV/MC/CHEM (98) 17" and in accordance with GLPStudy material is well characterized.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approx 9 weeks old
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: labeled Makrolon cages
- Diet: free access to pelleted rodent diet
- Water: ad libitum
- Acclimation period:

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

IN-LIFE DATES:

To: 18 June 2014
Completion : 14 July 2014

Vehicle:

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

Concentration:

In the pre-screen study: Two test substance concentrations were tested; a 100% and 50% concentration. The highest concentration was the maximum concentration as required in the test guidelines (undiluted for liquids, 50% for solids).

In the main study, three experimental groups of five female CBA/J mice were treated with test substance concentrations of 10, 25 or 50% w/w on three consecutive days, by open application on theears. Five vehicle control animals were similarly treated, but with vehicle alone (Acetone/Olive oil (4:1 v/v)).

No. of animals per dose:

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

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: not indicated
- 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.
- Lymph node proliferation response:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: LLNA
- Criteria used to consider a positive response: If the results indicate a SI ≥ 3, the test substance may be regarded as a skin sensitizer.

TREATMENT PREPARATION AND ADMINISTRATION: 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.
Correction of the purity/composition of the test substance is not applicable, since the test method requires a logical concentration range rather than specific dose levels to be dosed.
Administration:
Induction - Days 1, 2 and 3
The dorsal surface of both ears was topically treated (25 μL/ear) with the test substance concentration, at approximately the same time on each day.

Excision of the nodes - Day 6
Each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) (Merck, Darmstadt, Germany) containing 20 μCi of 3H-methyl thymidine (PerkinElmer Life and Analytical Sciences, Boston, MA, US).

Positive control substance(s):

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

Positive control results:

The six-month reliability check with Alpha-hexylcinnamaldehyde indicates that the Local Lymph Node
Assay as performed at WIL Research Europe is an appropriate model for testing for contact
hypersensitivity.

Parameter:

SI

Remarks on result:

other: The SI values calculated for the substance concentrations 10, 25 and 50% were 0.8, 1.7 and 4.8, respectively. SI results in table below

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Mean DPM/animal values for the experimental groups treated with test substance concentrations 10, 25 and 50% were 243, 539 and 1511 DPM, respectively. The mean DPM/animal value for the vehicle control group was 315 DPM. DPM values are presented for each animal and for each dose group in table below (other information)

 

Relative size lymph nodes, radioactivity counts (DPM) and Stimulation Index (SI)

 

Group	TS (%)^1	Animal	Size nodes^2 Left  Right	DPM^3/animal	Mean DPM ± SEM^4	Mean SI ± SEM
1	0	1 2 3 4 5	n            n n            n n            n n            n n            n	209 287 286 333 459	315 ± 41	1.0      0.2
2	10	6 7 8 9 10	n            n n            n n            n n            n n            n	218 188 245 336 227	243 ± 25	0.8 ± 0.1
3	25	11 12 13 14 15	n            n n            n n            n n            n n            n	289 526 1015 502 362	539 ± 127	1.7 ± 0.5
4	50	16 17 18 19 20	n            n n            n n            n n            n n            n	1008 2142 1168 2430 805	1511 ± 325	4.8 ± 1.2

1.     TS=test substance (%w/w).

2.     Relative size auricular lymph nodes(-,--or---:degree of reduction,+,++ or +++: degree of enlargement, n: considered to be normal).

3.     DPM=Disintegrations per minute

4.     SEM=Standard Error of the Mean

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

These results indicate that the test substance could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test substance concentration that will give a SI =3) of 35.4% was calculated.

Based on these results:
- according to the recommendations made in the test guidelines (including all amendments), Bis-Tes (dried) would be regarded as skin sensitizer.
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments), Bis-Tes (dried) should be classified as skin sensitizer (Category 1B).
- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), Bis-Tes (dried) should be classified as skin sensitizer (Category 1B) and labeled as H317: May cause an allergic skin reaction.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Migrated from Short description of key information:
One key study, an in-vivo local lymph node assay conducted following OECD and EU guidelines and under GLP conditions.

Justification for selection of skin sensitisation endpoint:
ASSESSMENT OF CONTACT HYPERSENSITIVITY TO BIS-TES (DRIED) IN THE MOUSE (LOCAL LYMPH NODE ASSAY) . Conducted according to OECD and EU guidelines and under GLP conditions.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

ASSESSMENT OF CONTACT HYPERSENSITIVITY TO BIS-TES (DRIED) IN THE MOUSE (LOCAL LYMPH NODE ASSAY) . The results indicate that the test substance could elicit a SI ≥ 3. The data showed a dose-response and an EC3 value (the estimated test substance concentration that will give a SI =3) of 35.4% was calculated. Therefore the test substance would be classified as a skin sensitizer 1.