Trimethoxypropylsilane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 Feb 1990 to 21 Feb 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)

Version / remarks:

adopted 12 May 1981

Deviations:

yes

Remarks:

Deviations unlikely significantly to affect the outcome of the study: excursions from recommended relative humidity and temperature; limited reporting of clinical observations.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trimethoxypropylsilane

EC Number:

213-926-7

EC Name:

Trimethoxypropylsilane

Cas Number:

1067-25-0

Molecular formula:

C6H16O3Si

IUPAC Name:

trimethoxy(propyl)silane

Test animals

Species:

rat

Strain:

other: Wistar derived Crl:WI(WU)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, GERMANY
- Age at study initiation: 7 weeks
- Weight at study initiation: mean - 218 g (males), 166 g (females)
- Fasting period before study: none stated
- Housing: (after exposure) 5 males or 5 females per suspended stainless steel cage
- Diet: standard diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): during exposure: mean 22.6; after exposure: 22 ± 3 (excursion 18.5 for 1 h)
- Humidity (%): during exposure: mean 79 ± 15 (relative humidity was above 70% for about 2 hours, during the rest of the exposure humidity was between 30 and 70%); after exposure: 30 - 70 (excursions 29, 74, 95 for 1 h on each occasion)
- Air changes (per hr): during exposure: 38; after exposure: 10
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1990-02-07 To: 1990-02-21

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: horizontal glass chamber; animals separated by perforated stainless steel plates
- Exposure chamber volume: 16 L (total volume)
- Method of holding animals in test chamber: see above
- Source and rate of air: 0.6 m³/h; flow velocity 34 m/h; ventilation frequency 38/h
- System of generating particulates/aerosols: heated air bubbled through heated test material at 35° C, passed through heated Pall filter (30° C) to remove aerosol as far as possible
- Method of particle size determination: to determine aerosol content: 11-stage cascade impactor
- Treatment of exhaust air: no details
- Temperature, humidity, pressure in air chamber: (mean of hourly measurements) 22.6° C; 79 ± 15%; pressure unstated

TEST ATMOSPHERE
- Brief description of analytical method used: hourly GC analysis
- Samples taken from breathing zone: yes

TEST ATMOSPHERE: 22.2 ± 6.9 g/m³ (4 measurements); nominal 59.8 g/m³; particle size tabulated (about 1% of the total test atmosphere consisted of aerosol).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Single exposure concentration:
22.2 ± 6.9 g/m³ (measured)
59.8 g/m³ (nominal)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily; body weights prior to exposure and on observation days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

None relating to LC50.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22 200 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

One of each sex died during exposure. One male died on observation Day 4 (see Table 2, Any other information on results incl. tables).

Clinical signs:

other: See field "Any other information on results incl. tables"

Body weight:

Body weights were generally not affected. Body weights were reduced in two females on Days 14, or 7 and 14 (see Attachment for tabulated data).

Gross pathology:

The lungs of the three animal that died during treatment or observation were discoloured red, spotted or swollen. No abnormalities were found in the remaining animals autopsied on Day 14.

Other findings:

None reported.

Any other information on results incl. tables

Clinical Signs

During the first 15 minutes of exposure animals were restless. Their eyes were half-closed and breathing was irregular. From 30 minutes and onward, rats seemed to be in narcosis, their breathing became deep and irregular. Directly after exposure, rats were still in narcosis. They showed dyspnoea and moist rales.

The first day of the 14-day observation period revealed wet nose and a dirty fur in several of the surviving rats. Thereafter, no abnormalities were observed. Just before death on Day 4 of the observation period, the male animal demonstrated lethargy, showed flabby muscles, incoordination, piloerection and a visually increased breathing frequency.

Exposure concentration and aerodynamic particle size

The mean actual concentration turned out to be 22.2 ± 6.9 g/m³. The standard deviation resulted from four measurements. The corresponding nominal concentration was 59.8 g/m³.

Particle size analysis is given in Table 1. The 50 percent accumulation point for the distribution was between 2.4 and 2.8 µm. However, the concentration of aerosol measured in this way turned out to be 0.2g/m³, indicating that a negligible amount of about one percent of the total test atmosphere consisted of aerosol.

Table 1: Aerodynamic particle size distribution

Aerodymamic diameter (µm)	Distribution % of total mass (22.2 g/m³)
<1	1.0
1	4.5
1.4	2.5
1.8	15.1
2.4	12.2
2.8	10.8
3.1	18.3
3.4	26.5
3.8	4.4
4.2	0.7
>4.2	3.9

Table 2: Concentrations, exposure conditions and mortality per animals treated

Nominal Conc. (g/m³)	Analytical Conc. (g/m³ ± SD )	Mortality (dead/total)
		Males	Females	Combined
59.8	22.2 +/- 6.9	2/5	1/5	3/10

 

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In an acute inhalation study according to OECD 403 and in accordance with GLP (reliability score 1) the LD50 for trimethoxy(propyl)silane was in excess of 22200 mg/m³ in the rat.