4-[fluoro(dimethyl)silyl]butanenitrile

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 23 - October 26, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

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:

4-[fluoro(dimethyl)silyl]butanenitrile

EC Number:

812-925-4

Cas Number:

1639345-42-8

Molecular formula:

C6H12FNSi

IUPAC Name:

4-[fluoro(dimethyl)silyl]butanenitrile

Test material form:

liquid

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: e.g. Envigo (formed partially from Harlan in September
2015), 5800 AN Venray, The Netherlands
- Age at the beginning of the study: 8–9 weeks
- Housing: IVC cages, type II L, polysulphone cages on Altromin saw fibre bedding (groups of 5 animals)
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum, tap water sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: adequate

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (LLNA)

Vehicle:

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

Concentration:

12.5%, 25% and 50% (v/v) (Based on the results observed in the prescreen test)

No. of animals per dose:

5

Details on study design:

PRE-SCREEN TESTS:
- Compound solubility:
The maximum technically applicable concentration of the test item was found to be 100%.
The maximum technically applicable concentration of the test item in the vehicle was found to be 50% in AOO (Acetone, Sigma-Aldrich, lot no. SZBF3480V, expiry date: 13/04/2017; olive oil highly refined, Sigma-Aldrich, lot no. BCBM3643V, expiry date: 04/12/2016).
Four animals were treated by topical application with the test item on three consecutive days at the following concentrations to the entire dorsal surface of each ear:
Animals no. 1 and no. 2 were treated with a test item concentration of 100% (undiluted)
Animals no. 3 and no. 4 were treated with a test item concentration of 50% (diluted with AOO)
One further animal was treated with 100% AOO and served as negative control.

- Irritation & Systemic toxicity:
Animal no. 1 treated with 100% of the test item did not show any signs of systemic toxicity or signs of irritation at any application site. Animal no. 2 was found dead 4 hours
after application. According to OECD 429 [4] application of 100% of test item was cancelled due to systemic toxicity effects in one animal (animal no. 2).
Neither signs of systemic toxicity nor signs of irritation at any application site could be detected in the animals treated with 50% in AOO (animal no. 3 and 4) and the control
animal (animal no. 5).

Positive control substance(s):

other: 1% phenylenediamine (Sigma-Aldrich, lot no.: WXBB8077V, expiry date 20/03/2017) in AOO was used as positive-control substance

Results and discussion

Positive control results:

Mean stimulation index 10.8 (standard deviation 1.6)

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

EC3

Value:

12.24

Remarks on result:

other: estimated by linear interpolation

Results 2

Parameter:

SI

Value:

3.1

Variability:

0.4

Test group / Remarks:

12.5%

Results 3

Parameter:

SI

Value:

4.8

Variability:

1.6

Test group / Remarks:

25%

Results 4

Parameter:

SI

Value:

8

Variability:

2.0

Test group / Remarks:

50%

Cellular proliferation data / Observations:

Measurement of Ear Thickness: The means of the ear thickness per group showed no relevant difference compared to
the negative control.

EC3 CALCULATION
The EC3 value was estimated by using the two doses closest to the SI value of three. The EC3 value was estimated by log-linear interpolation between these two points on a plane where the x-axis represents the dose
level and the y-axis represents the SI. The point with the higher SI is denoted (a,b) and the point with the lower SI is denoted (c,d). The formula for the EC3 estimate is as follows: EC3=2^{(log2(c)+(3-d)/(b-d)*[(log2(a)-log2(c)]}, by log-transforming the doses

CLINICAL OBSERVATIONS: All animals survived throughout the test period without showing any clinical signs.

BODY WEIGHTS: All animals showed the expected weight development, which includes a weight loss of
up to 2 g throughout the study.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The EC3 value (estimated by linear interpolation) was calculated to be at a test item concentration of 12.24%.
The measurement of the ear thickness did not reveal any relevant increase of the ear thickness in any dosage group.

Executive summary:

A skin sensitization test according to OECD 429 was performed. Based on the results of the prescreen test groups of 5 female CBA/CaOlaHsd mice each were treated with 12.5%, 25% and 50% v/v preparations of the test substance in Acetone/Olive Oil (4:1 v/v) or with the vehicle alone. All animals survived throughout the test period without showing any clinical signs. All animals showed the expected weight development, which includes a weight loss of up to 2 g throughout the study. The means of the ear thickness per group showed no relevant difference compared to the negative control. The EC3 value (estimated by linear interpolation) was calculated to be at a test item concentration of 12.24%. Therefore, 3-Cyanopropyldimethylfluorosilane is considered to be a dermal sensitiser under the test conditions chosen.