Isobutylisopropyldimethoxysilane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 January to 26 January 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with OECD Guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isobutylisopropyldimethoxysilane

EC Number:

402-580-4

EC Name:

Isobutylisopropyldimethoxysilane

Cas Number:

111439-76-0

Molecular formula:

Hill formula: C9H22O2Si

IUPAC Name:

dimethoxy(2-methylpropyl)(propan-2-yl)silane

Details on test material:

Substance: Isobutylisopropyldimethoxysilane TZ 01748 (Schering Code-No.: ZK 119.649)
Batch no,: FT 87/183
The liquid product ZK 119.649 contained 98. 5% dimethoxyisobutylisopropylsilane.
When stored in a closed container under exclusion of humidity, ZK 119.649 is stable for at least one year.

Test animals

Species:

rat

Strain:

other: Wistar-Han-Schering

Sex:

male/female

Details on test animals or test system and environmental conditions:

animal strain: Wistar-Han-Schering rat
animal quality: barrier sustained
animal number: 20 M, 20 F
breeder: Schering AG
body weight: 124-147g (M), 109-131g (F)
identification: ear slits
randomization: by lot
acclimatization: 7 days
caging conditions: conventional
cage type: Makrolon, typ<=> II with wiremesh bottom
feed type: pelleted Altromin R
type of drinking water: tap water
feeding time, watering time: ad libitum, except during exposure period
room temperature, minimum: 22°C
romm temperature, maximum: 22°C
relative humidity, minimum: 48 %
relative humidity, maximum: 74 %
light period: artificial lighting (12-hours day/night-rhythm)

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

Inhalation equipment
The dynamically operated inhalation system consisted of a generator unit to enrich air with vapour of ZK 119.649 and an exposure unit for nose-only exposure of the rats.

Generation of ZK 119.649 vapour-air mixtures
Dried compressed air was passed through a fine-particle filter, a pressure-stabilizer, a regulator and a ROTA flow meter. Then it was led through two special gas-washing bottles (70 mm diameter) with D1 sintered frits (d = 48 mm), connected in series. The bottles were filled with ZK 119.649 at a height of about 50 mm and kept at 20°C (+ 0.2°C) in a thermostated water-bath. For generation of graduated, defined mixtures of ZK 119.649 with
air, a second flow of air, processed and regulated as above, could be admixed in the requisite proportions, so that total volume flows of 1000 1 x h-1 (at 20°C, 1013 mbar) per chamber were accomplished. Before mixing with fresh air, aerosol particles were eliminated by an "on line" fiber glass filter (MILLIPORE, pore size less than or equal to 0.3 uM) from the generator line.

Exposure unit
The cylindric inhalation chambers of the Kimmerle type (60 L volume) were composed of an upper aerosol dispersion part and a lower exposure part with acrylic animal restraint tubes. The tubes were radially mounted to the chambers and designed such that only the noses of the animals were in contact with the aerosol flow in the chamber (nose-only exposure system). The exhaust air from the chamber was drawn under slight vacuum through a gas washing bottle with granulated charcoal (about 200 g) at a flow rate of 1000 1/h (+/- 5% at 20°C, 1013 mbar) which was controlled by a flow-meter.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.66 g x m-3
2.7 g x m-3
3.3 g x m-3
4.0 g x m-3

Higher concentrations were not tested, because exposure at a practically saturated vapour concentration of 4.4 g x m ZK 119.649 had already produced mortality after 125 min in a previous inhalation hazard test.

No. of animals per sex per dose:

5 male + 5 female per dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test animals were observed repeatedly during exposure and three times after exposure on day 1 (day 1 = day of exposure). During the following observation period until day 14, a careful clinical examination and an additional check for dead and moribund animals were performed once daily. Body weights were recorded on day 1 (prior to treatment), 8 and 14 .
- Necropsy of survivors performed: yes. All animals were sacrificed at the end of the observation period (day 14) and autopsied. All gross pathological changes were recorded.
- Other examinations performed: clinical signs, body weight.

The actual chamber concentrations of the product were determined by gas chromatography.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4 000 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths during the exposure or in the 14 day observation period.

Clinical signs:

other: Prominent clinical findings during exposure were irregular respiration in all groups and respiratory distress and drawn in flanks at the two high concentrations. Additionally in one animal each at the highest concentration marked sialorrhea and spontaneou

Body weight:

No definite effects of exposure on weight gain were observed.

Gross pathology:

At necropsy, no exposure related macroscopic alterations were found.

Other findings:

None

Any other information on results incl. tables

In summary, the following prominent clinical signs were regarded as effects of exposure to ZK 119.649:

During exposure:

in all groups: irregular respiration

in group 4 and 5: respiratory distress, drawn in flanks

in group 5: in one animal each: marked sialorrhea, spontaneous total spasmodic twitches

After exposure:

in all groups: ruffled and wet, sticky fur

in group 3: slight apathy

in group 4 and 5: slight to severe apathy, atactic gait

additionally in

group 5: spontaneous total tremor, prone position conscious (in 1 M)

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An acute inhalation toxicity study was conducted with the test substance in agreement with the test guidelines of the OECD (no. 403, adopted May 12, 1981). The LC50 of the test substance (as aerosol) for male and female rats may be given as follows: LC50 (4 h) > 4.0 g/m3.

Executive summary:

An acute inhalation toxicity study was conducted with the test substance in agreement with the test guidelines of the OECD (no. 403, adopted May 12, 1981). The LC50 of the test substance (as aerosol) for male and female rats may be given as follows: LC50 (4 h) > 4.0 g/m3.