Trimethoxyoctylsilane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08.01.1990 to 22.02.1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxyoctylsilane

EC Number:

221-338-7

EC Name:

Trimethoxyoctylsilane

Cas Number:

3069-40-7

Molecular formula:

C11H26O3Si

IUPAC Name:

trimethoxyoctylsilane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Wiga, Sulzfeld, FRG.
- Age at study initiation: 7-11 weeks
- Weight at study initiation: 260-170 g
- Fasting period before study: No data
- Housing: In between exposures in suspended stainless steel cages (5 animals/cage), and during exposure housed individually
- Diet (e.g. ad libitum): Ad libitum (except during exposure when food was not available)
- Water (e.g. ad libitum): Ad libitum (except during exposure when food was not available)
- Acclimation period: From arrival to start of study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 08.01.1990 to 22.02.1990

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

other: whole body for first part of study and nose-only for second part.

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body: horizontally placed, all glass cylinder, separated from other animals by a perforated stainless steel plates. Ports in the middle and at the end of the cylinder allowed sampling of the test substance. Nose-only: nose-only inhalation chamber type 8132 P2. Only the nose of the rats was protruding into the exposure chamber.
- Source and rate of air: No information on source. Rate for whole body exposure 10 l/min, for nose
- System of generating particulates/aerosols: the test atmosphere was generated by bubbling the total flow of heated air through the heated test substance. In this way the air flow became saturated with test substance. Since the concentration obtained in this way was not sufficiently high, test atmospheres for the other concentrations were generated in a different way. A sample of test substance was poured into a flask. A roller pump passed metered amounts of the test substance from the flask to a Lee 150H nebuliser connected at the top of the chamber. The air volume through the nebuliser was at maximum. The generated aerosol was diluted with clean air from the compressed air system. The aerosol was directed downwards through the mixing chambers towards the noses of the animals.
- Method of particle size determination: 11-stage cascade impactor.
- Treatment of exhaust air: Passed out from the bottom of the chamber - no further details .
- Temperature, humidity, pressure in air chamber: Whole body: 19.8 ±0.3oC, 80 ±4%, slight negative pressure. Nose-only: 18.2 oC, 69%, slightly positive pressure.

TEST ATMOSPHERE
- Brief description of analytical method used: The actual mass concentration of the test substance in the test atmosphere was determined each hour by means of gas chromatography.
- Samples taken from breathing zone: no data

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Mean actual concentrations: 0.9, 2.36, 2.53 and 6.2 g/m3.
Corresponding nominal concentrations: 3.5, 9.8, 15.4 and 27.6 g/m3.

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were visually inspected during the exposure period, and once daily during the observation period. Body weights were recorded just prior to exposure and at days 7 and 14.
- Necropsy of survivors performed: yes, at the end of the observation period, all surviving rats were killed and examined for gross pathological changes.

Statistics:

The LC50 was calculated using Probit analysis.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

7.5 other: g/m3

Based on:

test mat.

95% CL:

>= 4.3 - <= 29.7

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

1.9 other: g/m3

Based on:

test mat.

95% CL:

>= 1 - <= 3.1

Exp. duration:

4 h

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.9 other: g/m3

Based on:

test mat.

Exp. duration:

4 h

Mortality:

See Table 1. All deaths occurred within days 1-3.

Clinical signs:

other: During exposure to 0.9 g/m3 animals showed hunched appearance, piloerection and mostly closed eyes. Breathing patterns were superficial and irregular during the first hour of exposure. Then, breathing patterns became more regular concomitant with a decrea

Body weight:

All four surviving rats exposed to 6.2 g/m3 showed severe body weight reduction seven days after exposure. However, body weight gain was observed 14 days after exposure in three out of four rats. Exposure to 0.9 g/m3 resulted in body weight gain reduction in male rats 14 days after exposure, and in decreased body weight or reduced body weight gain in female rats 7 and 14 days after exposure. Body weight gain of the other survivors exposed to 2.53 or 2.36 g/m3 was generally not affected by exposure.

Gross pathology:

At autopsy, dark-red discoloured, and sometimes swollen or darkly spotted, and/or edematous lungs were found in animals that died, or were killed in extremis after exposure to 6.2 g/m3. Furthermore, grey-white spots were observed on the lung lobes of three female rats. Exposure to 2.53 g/m3 revealed rusty-brown discoloured lungs. Red discoloured lungs were found in rats exposed to 2.36 g/m3. In the other rats that were killed in extremis no abnormalities were observed. In all surviving rats autopsied at the end of the 14-day observation period, no abnormalities were found, except for spotted lungs in one male exposed to 6.2 g/m3.

Other findings:

None

Any other information on results incl. tables

The 50% accumulation point for all four distributions was around 2.4 µm. All distributions showed a similar pattern: about 60% (exposure to 6.2 g/m³) to 89% (exposure to 0.9 g/m³) of the particles were between 1.8 and 3.4 µm in diameter.

Table 1 Summary of concentrations and mortality data

Group	Concentration (g/m3)		Mortality
	Actual	Nominal	Males (number tested/deaths)	Female (number tested/deaths)
A	0.9 ± 0.32	3.5	5/0	5/0
B	6.2 ± 0.6	27.6	5/1	5/5
D	2.53 ± 0.64	15.4	5/0	5/4
E	2.36 0.31	9.8	5/1	5/3

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In an inhalation study conducted according to OECD Test Guideline 403 and in compliance with GLP (reliability score 1) the LC50 for trimethoxyoctylsilane was 7.5 and 1.9 g/m3 for males and females, respectively. The combined LC50 was 3.9 g/m3. Clinical effects included reduced body weights, slow breathing, piloerection and signs of ataxia.