4-[fluoro(dimethyl)silyl]butanenitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 22 - July 20, 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:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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

Test animals

Species:

rat

Strain:

other: WISTAR rats Crl: WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Weight at study initiation: males: 237 – 242 g, females: 205 – 232 g
- Housing: The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw
fibre bedding
- Diet: ad libitum, Free access to Altromin 1324 maintenance diet for rats and mice
- Water: ad libitum, Free access to tap water, sulphur acidified to a pH value of approximately 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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Approximately 24 hours before the test, the fur was removed from the dorsal area of the trunk using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact
skin were used.
No less than 10% of the body surface was cleared for the application.
The test item was held in contact with the skin by a dressing throughout a 24-hour period. This consisted of a semi-occlusive dressing made of a porous gauze and non-irritating tape and was fixed
with an additional dressing in a suitable manner.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing (at least once during the
first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the
animals were observed for clinical signs once daily until the end of the observation period. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Gross necropsy of survivors performed: yes
- Other examinations performed: Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All signs of irritation were reversible within the observation period.

Mortality:

No mortality occured.

Clinical signs:

No signs of systemic toxicity were observed.
Erythema up to grade 2 was observed in all animals. Crust was observed in 1 of 5 male and 3 of 5 female animals. Desquamation was observed in 5 of 5 male and 3 of 5 female animals. No oedema was observed. All signs of irritation were reversible within the observation period.

Body weight:

A slight weight loss was recorded for 2 out of 5 female animals (no. 27 and 28) during the first week,
but all of the female animals showed weight gain during the second week. The effects on weight
development might be secondary to the dressing, and toxicological relevance of this finding cannot
clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the
euthanasia injection, no specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, single dermal application of the test item 3-Cyanopropyldimethylfluorosilane to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity but signs of irritation.

Executive summary:

The test item was administered topically at a single dose (2000 mg/kg BW) by applying uniformly over an area which was approx. 10% of the total body surface. 5 male animals (WISTAR Crl: WI(Han) rats) as well as 5 female animals (WISTAR Crl: WI(Han) rats) were used.

Test item was held in contact by an semi-occlusive dressing with the skin throughout a 24-hour period. This consisted of a semi-occlusive dressing made of a porous gauze and non-irritating tape and was fixed with an additional dressing in a suitable manner.

At the end of the exposure period the residual test item was removed using aqua ad injectabilia (AlleMan Pharma, lot no. 511535, expiry date: 01/2018).

A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). At the end of the observation period the animals were sacrificed and necropsy was carried out to record gross pathological changes.

No signs of systemic toxicity were observed. Erythema up to grade 2 was observed in all animals. Crust was observed in 1 of 5 male and 3 of 5 female animals. Desquamation was observed in 5 of 5 male and 3 of 5 female animals. No oedema was observed. All signs of irritation were reversible within the observation period. Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animals.

Therefore, according ot OECD Guideline 402, a sufficient estimation of the acute dermal toxicity of the test item is provided.