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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2017-09-05 to 2017-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetravinylsilane
EC Number:
214-192-0
EC Name:
Tetravinylsilane
Cas Number:
1112-55-6
Molecular formula:
C8H12Si
IUPAC Name:
tetraethenylsilane
Test material form:
liquid
Specific details on test material used for the study:
Lot number: 707001
Purity: 98.6%
Appearance: Colourless tranparent liquid
Storage conditions: Refrigerator (1-10°C) in an air-tight container

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Source: Charles River Laboratories, Japan (Hino Breeding Center)
Age of animals on receipt: Seven weeks
Quarantine/acclimatisation period: Seven days
Age at time of administration: Eight weeks (first and second step; 300 mg/kg bw); Nine weeks (third and fourth step; 2000 mg/kg bw).
Body weight at time of administration: 189.6-195.0g (first step; 300 mg/kg bw dosing); 188.1-195.1g (second step; 300 mg/kg bw dosing); 195.7-203.8g (third step; 2000 mg/kg bw dosing); 186.8-192.4g (fourth step; 2000 mg/kg bw)
Temperature: 21-25°C
Relative humidity: 40-70%
Air changes: 10-15/hour
Photoperiod: 12 hours light/dark cycle
Caging: Stainless steel cages with mesh floor
Housing: Up to 3/cage during acclimatisation; Individual until dosing
Feed: Pellet diet (MF; Oriental Yeast); ad libitum
Water: Chlorinated water (chlorine at 3-5 ppm) by adding sodium hypochlorite to Hita City mains supply; ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
Concentration of dosing formulation: 3.00% w/v (300 mg/kg bw); 20.0% w/v (2000 mg/kg bw)
Dosing volume: 10 mL/kg bw
Rationale for dosing: No toxicity data available therefore first step was 300 mg/kg bw
Animals fasted for 18-19 hours before administration and for 3-4 hours after administration
Dosing based on body weight measured on the day of dosing
Doses:
300 mg/kg bw (first and second step)
2000 mg/kg bw (third and fourth step)
No. of animals per sex per dose:
Three females/dose for each step
Control animals:
no
Details on study design:
Animals dosed with 300 mg/kg bw for the first and second steps were observed continuously for 10 minutes after dosing, 30 minutes and 3 hours after administration and then daily from 1 to 14 days after administration.
Animals dosed with 2000 mg/kg bw for the third and fourth steps were observed continuously for 10 minutes after dosing, 30 minutes, 1, 3 and 5 hours after administration and once on the morning after dosing. Additional observations in the evening were performed the day after dosing for the thirs step and for the first two days after dosing for the fourth step.

Body weights were measured before administration, then 1, 7 and 14 days after dosing.
Animals were subjected to a gross necropsy 14 days after dosing.
Animals were euthanised by bleeding from the abdominal aorta under isoflurane anaesthesia. External surface of the body, all orifices, subcutis, cranial, thoracic, abdominal and pelvic cavities with their contents were observed.
Statistics:
Not required.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Mortality:
No mortalities or moribundities for any treatment.
Clinical signs:
other: At 300 mg/kg bw, mucus stools were observed in four animals 30 minutes or 3 hours after dosing. This finding was attibuted to the effect of the vehicle since this was not dose dependent and historical data show this has occured in 38/135 females following
Gross pathology:
No abnormalities were observed at 300 or 2000 mg/kg bw.
Other findings:
None

Any other information on results incl. tables

Clinical signs

Clinical sign

Dose group

300 mg/kg bw

(first step)

300 mg/kg bw

(second step)

2000 mg/kg bw

(third step)

 

2000 mg/kg bw (fourth step)

 

Salivation

0/3

0/3

0/3

1/3

Mucus stool

1/3

3/3

0/3

0/3

Decreased stool volume

0/3

1/3

0/3

0/3

Decreased spontaneous locomotion

0/3

0/3

3/3

3/3

Decreased respiratory rate

0/3

0/3

3/3

3/3

Incomplete eyelid opening

0/3

0/3

3/3

3/3

Restlessness

0/3

0/3

1/3

1/3

Lacrimation

0/3

0/3

0/3

1/3

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Not classified
Conclusions:
The LD50 cut off value of test item defined as 5000 mg/kg bw or unclassified since no mortalities or moribundities occurred at 2000 mg/kg bw.
Executive summary:

A GLP compliant study was conducted to determine acute oral toxicity of test item according to OECD 423. Three female Crl: CD (SD) rats were initially administered with 300 mg/kg bw. Since no mortalities or moribundities were observed, a further group of three females were dosed with 300 mg/kg bw. Since the findings in this additonal group were consistent with the first treatment group, the dose was increased to 2000 mg/kg bw for a further group of three females. Since no mortalities or moribundities were observed in this group, a further three females were dosed with 2000 mg/kg bw. Clinical signs were observed continuously for the first 10 minutes, then at longer intervals up to 5 hours after dosing and at least once daily up to the end of the observation period of 14 days following test substance administration. Body weight was recorded throughout. The animals were then subject to gross necropsy. External surface of the body, all orifices, subcutis, cranial, thoracic, abdominal and pelvic cavities with their contents were examined. No mortalities or moribundities were observed. A slight decrease in body weight gain was noted in two animals dosed with 2000 mg/kg bw one day after administration. There were no clinical signs at 300 mg/kg bw. At 2000 mg/kg bw, decreased spontaneous locomotion was observed in all six animals from 30 minutes after dosing which persisted until one or two days after administration. Decreased respiratory rate and incomplete eyelid opening was also noted in all six animals within 1 hour of dosing which persisted until the following day for only the second group dosed with 2000 mg/kg bw. Salivation was observed in one animal 30 minutes after administration. Restlessness was noted in two animals and lacrimation in one animal 1 hour after dosing. No other abnormalities were observed three days after dosing or for the remaining observation period for the higher dose animals. No abnormalities were noted during gross necropsy. The LD50 cut off value of test item defined as 5000 mg/kg bw or unclassified since no mortalities or moribundities occurred at 2000 mg/kg bw.