Trimethylvinylsilane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12.12.2017-18.01.2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

yes

Remarks:

techincal reason: the starvation was prolonged for 7 minutes. This deviation did not influence the quality or the integruty of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

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:

Trimethylvinylsilane

EC Number:

212-042-9

EC Name:

Trimethylvinylsilane

Cas Number:

754-05-2

Molecular formula:

C5H12Si

IUPAC Name:

trimethylvinylsilane

Specific details on test material used for the study:

purity: 99.59%

Test animals

Species:

rat

Strain:

Wistar

Remarks:

WISTAR rats Crl: WI(Han) (full barrier)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: purchased from commercial supplier
- The animals were derived from a controlled full-barrier maintained breeding system (SPF)
- Age at the beginning of the study: 8 – 10 weeks old
- Sex: female (non-pregnant and nulliparous)
- Body weight on the day of administration:
-- Step 1: 159 – 173 g
-- Step 2: 149 – 165 g
-- Step 3: 167 – 173 g
- Number of animals: 3 per step

HOUSING AND FEEDING CONDITIONS
- Full barrier in an air-conditioned room
- Temperature: 22 ± 3 °C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- 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)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.

Doses:

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

No. of animals per sex per dose:

3 per step

Control animals:

no

Details on study design:

Preparation of the Animals:
The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to approximately 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Observation Period:
The animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Weight Assessment:
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15

Clinical Examination:
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.
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.

Pathology:
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Evaluation of Results:
Results were interpreted according to OECD Guideline 423, Annex 2 and GHS.
Individual reactions of each animal were recorded at each time of observation.
Toxic response data was recorded by dose level.
Nature, severity and duration of clinical observations was described.
Body weight changes were summarised in tabular form.
Necropsy findings were described.
With few exceptions, data was captured using the validated departmental computerised system E WorkBook (version 10.1.2, ID Business Solutions Ltd.).

The deviation ftom the study plan did not influence the quality or integrity of the present study (the starvation period prior to administration of the test item was slightly prolonged).

Statistics:

not applicable

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: 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, piloerection, half eyelid-closure, ataxia and hunched posture. All symptoms recovered within up to 2 days post-dose.

Gross pathology:

No specific gross pathological changes were recorded for any animal

Other findings:

Not specified

Any other information on results incl. tables

Results per Step

Step	Sex / No.	Starting Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths
1	Female / 1 - 3	300	3	0
2	Female / 4 - 6	2000	3	0
3	Female / 7 - 9	2000	3	0

LD50 Cut-Off

Starting Dose (mg/kg bw)	Number of animals	Number of intercurrent deaths	LD50 Cut-Off (mg/kg bw)
300	3	0	5000
2000	6	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of Vinyltrimethylsilane after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): 5000 mg/ kg bw

Executive summary:

This study has been performed in order to investigate the toxic properties of the test substance after a single oral administration.

One group of three female WISTAR Crl: WI(Han) rats was treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight (step 1). No compound-related mortality was recorded for any animal of step 1. Based on these results further testing was performed.

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 2000 mg/kg body weight (step 2 and 3). No compound-related mortality was recorded for any animal of step 2 and 3.

The study was performed in accordance to OECD TG 423 and in compliance to GLP.

All animals used in the study after their entrance were allowed to acclimatise to the laboratory conditions for at least 5 days.

The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

The test item showed no mortality but acute oral toxicity characteristics after a single dose administration. 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, piloerection, half eyelid-closure, ataxia and hunched posture. All symptoms recovered within up to 2 days post-dose.

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, piloerection, half eyelid-closure, ataxia and hunched posture. All symptoms recovered within up to 2 days post-dose.

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

At necropsy, no macroscopic findings were observed in any animal of any step.

Under the conditions of the present study, a single oral application of the test item Vinyltrimethylsilane to rats at a dose of 300 mg/kg body weight was associated with signs of toxicity but not mortality.

Under the conditions of the present study, a single oral application of the test item Vinyltrimethylsilane to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity but not mortality.

The median lethal dose of Vinyltrimethylsilane after a single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): 5000 mg/ kg bw.