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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2019-07-26 to 2019-08-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report date:
2019

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
2009
Deviations:
yes
Remarks:
The temperature and relative humidity of housing room have small deviations, not affect the quality and integrity of the study
GLP compliance:
yes (incl. QA statement)
Test type:
fixed concentration procedure
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:
tetravinylsilane
Test material form:
liquid
Specific details on test material used for the study:
Batch No.: 707001
Purity: 98.5%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: SPF (Beijing) Biotechnology Co., Ltd.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 57~64 days
- Weight at study initiation: 330~372g for male rats and 234~239g for female rats
- Fasting period before study: not fasted
- Housing: Animals were raised in suspended, stainless steel cages (L32.0cm ×W28.0cm×H20.0cm) on cage racks (L167.0cm×W70.0cm×H171.0cm). There were 10 cages per layer, and 4 layers per rack. Animals were housed individually after exposure.
- Diet: ad libitum except restraining period
- Water: ad libitum except restraining period
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5°C ~25.9°C
- Humidity (%): 50% ~72%
- Photoperiod: 12 hour light and 12 hour dark

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
>= 1.16 - <= 1.31 µm
Geometric standard deviation (GSD):
>= 2.75 - <= 2.84
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: HOPE-MED 8052Hdynamic snout-only aerosol inhalation instrument (Equipment No. W-23)
- Exposure method:
Before exposure, each rat was restrained in a confined transparent polyacrylic tube. The exposure tubes wereinstalled in the portholes of the inhalation chamber and the chamber was sealed up. Filtered and compressed air was mixed with quantitative test item and aerosol was sent to exposure chamber (0.04m3). The test item moving speed and exposure airflow rate had been adjusted. The aerosol had been continuously generated from generation system on the top of the chamber with an aerosol producer. A slight negative pressure was maintained in outer plenum of chamber to prevent leakage of the test substance into the surrounding area. The exhausted air was removed from the outlet at the bottom of the chamber to absorption unit.
- Particle size distribution determination: Twice, at the beginning and at the end of exposure using Aerosol Instrument for Aerodynamic Particle Sizer® (APS™) 3321

TEST ATMOSPHERE
- Brief description of analytical method used: Actual concentration at the animals' breathing zone was determined by using filter gravimetric analysis. Samples were collected by usingfiber filter fixed in filter holder attached to ESA-3Z auto-sampling device, on which airflow(1 L/min), time (5 min) and volume (5 L) was set. The mass collected filter paper was weighed before (M1) and after collection (M2). The collected mass was calculated by the following formula: (M) = M2-M1. Actual concentration (C, mg/m3) = the collected mass (M, mg)/ the collected volume (V, L) ×1000 L/m3. Frequency of determination was aboutonce per hour.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Maximum attainable concentration: 2270 mg/m3
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were recorded once during the exposure and twice with more than 30 minutes interval after exposure on the exposure day and then once daily for up to end observation.
The animals were weighed in the first 24 hours after arrival, on the day of exposure prior to exposure (day 0), and on day 1, day 3, day 7 and day 14.
- Necropsy of survivors performed: yes, All surviving animals at the end of the study and that which died during the test were subjected to gross necropsy.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2 270 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One male animal was found dead during the exposure on the exposure day, the mortality was 17% (1/6).
Clinical signs:
other:
Body weight:
The body weights of three animals decreased on the Day 1 and increased on the Day 3 after exposure.
The body weight of one animal showed no change on the Day 1 and increased on the Day 3 after exposure.
The body weight of one animal showed increased trendduring the observation period.
Gross pathology:
No abnormalities were found in female and male animals at the gross necropsy.

Any other information on results incl. tables

 Calculated MMAD, GSD and Inhalable Fraction

Actual Concentration

Times

MMAD (µm)

GSD

<4 µm (mass%)

(mg/m3)

2270

First

1.16

2.75

66%

Second

1.31

2.84

63%

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute inhalation LC50 in SD rats for test item was more than 2270 mg/m3 (2.27 mg/L).
Executive summary:

The acute inhalation toxicity of test after being snout only administrated to SD rats for 4 hours was assessed at the maximum attainable concentration of 2270 mg/m3based on OECD 403.

One male animal was found dead during the exposure on the exposure day, the mortality was 17% (1/6).

One male animal showed tremor, dyspnea and convulsion, and one male animal and three female animals showed no abnormalities during the exposure.

The animals showed unkempt fur (4/5), blooding discharge around the nose (4/5), and secretions around the nose and mouth (2/5) on the first and second time observation after exposure on the exposure day.

One male animal showed unkempt fur, and one male animal and three female animals showed no abnormalities on the Day 1 after exposure. All surviving animals (5/5) showed no abnormalities on the Day 2-14 after exposure.

The body weights of three animals decreased on the Day 1 and increased on the Day 3 after exposure. The body weight of one animal showed no change on the Day 1 and increased on the Day 3 after exposure. The body weight of one animal showed increased trend during the observation period.

No abnormalities were found in female and male animals at the gross necropsy.

Based on the results, the acute inhalation LC50in SD rats for test item was more than 2270 mg/m3(2.27 mg/L).

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