Tetrapropyl orthosilicate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1991/07/23 - 1991/08/28

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP. Read across to the registered substance is considered scientifically justified; the read across is considered to be reliability 2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

other: LC50

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetraethyl orthosilicate

EC Number:

201-083-8

EC Name:

Tetraethyl orthosilicate

Cas Number:

78-10-4

IUPAC Name:

tetraethyl orthosilicate

Test animals

Species:

rat

Strain:

other: Wiskf(SPF71)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: HOECHST AG, Kastengrund, SPF-Zucht

- Age at study initiation: 8-10 weeks

- Weight at study initiation: Male rats weighed 193-234 g at the time of dosing and  female rats weighed 190-202 g at dosing. 

- Housing: the animals were housed in aan airconditioned room in Makrolon type 4 cages, 5 animals per cage

- Diet: Rat diet Altromin 1324, ad libitum

- Water: tap water, ad libitum




ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 +/- 2C

- Humidity (%): 50 +/- 20%

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: The test substance was injected into the chamber at constant velocity through an infusion apparatus at one end of the chamber.

- Exposure chamber volume: 60 litres

- Method of holding animals in test chamber: The animals were in a stainless steel and glass cylinder, with plastic tubes leading to the exposure cylinder designed so that the animal's noses fit inside.

- Source and rate of air: The air supply was kept constant at 800 l/h through a calibrated rotameter.

- Method of conditioning air: A suction device at the bottom of the inhalation chamber enabled the air to be paseed through, attached to a water bottle, a Buehler filter and a bottle of calcium chloride.

- System of generating particulates/aerosols: The primary aerosol formation took place in the generation flasks, and the smaller particles were passed into the inhalation chamber through a riser pipe.

- Method of particle size determination:  Determination of the particle size was only possible at the highest concentration because the test substance was mostly in the gaseous phase as the concentrations decreased.

- Treatment of exhaust air: Exhaust air was extracted and neutralised.

- Temperature, humidity, pressure in air chamber: An air monitoring system (Hartmann & Braun) continuously recorded CO, CO2, O2, humidity and temperature in the exposure chamber.


TEST ATMOSPHERE

- Brief description of analytical method used: For the determination of the test material concentration in the inhalation chamber, 31 liters of the test atmosphere during a 60 minute period of the exposure period was analysed by passing it through a series of connected gas wash bottles which were completely filled with 70, 60 and 50 ml absolute ethanol residing in a cold bath. The distribution of aersol particle size was determined using an Anderson-Cascade Impactor 3 (Anderson Samples Inc, Atlanta). Mean relative abundances of aerodynamic diameter were determined . The device was operated at a vacuum flow rate of 9.5 litres/minute, from which a flow velocity of 1.25 m/secon was calculated.

- Samples taken from breathing zone: yes



TEST ATMOSPHERE (if not tabulated)

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.8 micrometers / 1.7.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas chromatography using an FID as a detector.

Duration of exposure:

4 h

Concentrations:

5.74, 9.98, 10.40 and 16.83 mg/liter

No. of animals per sex per dose:

5M, 5F per dose, except no females at the 5.74 mg/liter dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Rats were observed for clinical symptoms during the 4 hour exposure period and then twice per  
day for 14 days post exposure. Body weights were determined prior to dosing and on days 8 and 15 of the study.  

- Necropsy of survivors performed: yes

Statistics:

The LC50, 95% confidence limits were calculated according to Fieller and Sidak and probit analysis was carried out on the mortality data according to Finney and Weber.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

10 mg/L air

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

> 16.8 mg/L air

Exp. duration:

4 h

Mortality:

Deaths first occurred on or just before the 3rd test day. Please see Table 1.

Clinical signs:

other: The animals showed  reactions involving motor behavior and respiration, palpebral stenosis extending to full lid closure with encrusted blood covered eyelid rims,  shivering and tonic cramping. Cyanosis and decreased reflexes occurred in individual animal

Body weight:

Body weights were decreased during the study but by the completion of the study, all the animals exceeded their initial weight. 

Gross pathology:

Necropsy results from animals which died during the study showed red and orange coloured lungs, release of froth upon incision of the lungs and  lung spotting. Spotting or light colouration of the lungs were found in every female rat sacrificed at the end of the study. There were no macroscopic findings in the male rats sacrificed at the end of the study.

Other findings:

Surviving female animals were reported to have mottled lungs, whereas this was not seen in the males.

Any other information on results incl. tables

Table 1: Concentrations, exposure conditions and mortality per animals treated

Analytical Conc. (mg/L)	Mortality (# dead/total)
	Males	Females	Combined
5.74	1/5	-	1/5
9.98	2/5	0/5	2/10
10.40	3/5	1/5	4/10
16.83	4/5	1/5	5/10

 

Value [LC50] with 95 % confidence limits was: 10.0 mg/l for male rats and 16.8 mg/l for female rats. 

Applicant's summary and conclusion

Interpretation of results:

other: not specified

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

The LC50 value of 10.0 mg/l in male rats and >16.8 mg/l in female rats was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.