4-[fluoro(dimethyl)silyl]butanenitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 10 - June 16, 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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

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:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Weight at study initiation: step 1: 146 – 165 g; step 2: 147 – 178 g; step 3: 143 – 156 g
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw
fibre bedding
- Diet: Free access to Altromin 1324 maintenance diet for rats and mice
- Water: 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

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

step 1: 300 mg/kg bw
step 2: 300 mg/kg bw
step 3: 2000 mg/kg bw

No. of animals per sex per dose:

3 females per step

Control animals:

no

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). As soon as
symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs
once daily until the end of the observation period. All abnormalities were recorded. The animals were weighed on day 1 (prior to the administration) 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. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma..

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Mortality:

Step 1: female, 300 mg/kg bw; number of animals: 3, number of deaths: 1
Step 2: female, 300 mg/kg bw, number of animals: 3, number of deaths: 0
Step 3: female: 2000 mg/kg bw; number of animals: 3, number of deaths: 3

Clinical signs:

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg
bw were reduced spontaneous activity, moving the bedding, hunched posture, slow movements,
ataxia, piloerection, eyes half closed, eyes closed and salivation. The clinical signs persisted until
intercurrent death on day 2 or on day 3 of treatment.
The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg
bw were reduced spontaneous activity, moving the bedding, recumbency, hunched posture, wasp
waist, piloerection and eyes half closed. In the surviving animals (5 out of 6), all symptoms
recovered within the next day.

Body weight:

Throughout the 14-day observation period, the weight gain of the surviving animals was within the
normal range of variation for this strain.

Gross pathology:

Macroscopic findings of surviving animals:
At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.
Macroscopic findings of animals not having survived until the end of the observation period:
Necropsy revealed either mucous or blood with or without residual test item in the stomach.
Additionally, in most of the animals which had died intercurrently, either blood or a gaseous
distension were found in the intestine.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of the present study, a single oral application of the test item 3-
Cyanopropyldimethylfluorosilane to rats at a dose of 300 mg/kg body weight was associated with
signs of toxicity and mortality.
Under the conditions of the present study, a single oral application of the test item 3-
Cyanopropyldimethylfluorosilane to rats at a dose of 2000 mg/kg body weight was associated with
signs of toxicity and mortality.
The median lethal dose of 3-Cyanopropyldimethylfluorosilane after a single oral administration to
female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 500 mg/ kg bw

Executive summary:

The acute toxic class method according to OECD Guideline No. 423 was performed with the test item. It is the princicple of the acute toxic class methode that, based on a stepwise procedure with the use of a minimum number animals per step, sufficient information is obtained on the acute toxicity of the test item to enbale its classification.

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was dissolved in the vehicle corn oil at a concentration of 0.03 g/mL and administered at a dose volume of 10 mL/kg. One group of three female WISTAR Crl: WI(Han) rats was treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved in the vehicle corn oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

One animal treated with the test item at a dose of 300 mg/kg and all animals treated with the test item at a dose of 2000 mg/kg were found dead on day 2 or on day 3 of treatment. All remaining animals survived until the end of the study showing signs of toxicity on the day of treatment. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, moving the bedding, hunched posture, slow movements, ataxia, piloerection, eyes half closed, eyes closed and salivation. The clinical signs persisted until intercurrent death on day 2 or on day 3 of treatment. The most relevant clinical findings in the animals treated with the test item at a dose of 300 mg/kg bw were reduced spontaneous activity, moving the bedding, recumbency, hunched posture, wasp waist, piloerection and eyes half closed. In the surviving animals (5 out of 6), all symptoms recovered within the next day.

Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain. Macroscopic findings of surviving animals: At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Macroscopic findings of animals not having survived until the end of the observation period: Necropsy revealed either mucous or blood with or without residual test item in the stomach. Additionally, in most of the animals which had died intercurrently, either blood or a gaseous distension were found in the intestine.

According to the acute toxic class method regime, no further testing was required.

Therefore, according to OECD Guideline 423, a sufficient estimation of the acute oral toxicity of the test item is provided.