Diethoxy(methyl)silane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 Mar - 05 May 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

On April 28, 1999, the temperature and humidity of the animal room were not recorded for the Group 4 rats. A pre-exposure analytical sample of the chamber concentration prior to Group 1 animal exposure was not taken as required by the protocol.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diethoxy(methyl)silane

EC Number:

217-982-3

EC Name:

Diethoxy(methyl)silane

Cas Number:

2031-62-1

Molecular formula:

C5H14O2Si

IUPAC Name:

diethoxy(methyl)silane

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Y-1205
- Physical state: clear liquid
- Stability under test conditions: Presumed stable for 3 weeks
- Storage condition of test material: at room temperature, Nitrogen Headspace

Test animals

Species:

rat

Strain:

other: Sprague-Dawley (Crl:CD VAF/Plus)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Kalamazoo, Michigan, USA
- Weight at study initiation: 271 - 324 g (males), 195 - 227 g (females)
- Age at study initiation: 8 weeks
- Housing: Animals were individually housed in suspended, stainless steel, wire-mesh cages.
- Diet: Certified Rodent chow #5002, PMI Nutrition International, Inc., St. Louis, Missouri, USA, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: 7 – 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3 – 23.3
- Humidity (%): 30 – 62
- Air changes (per hr): at least 12
- Photoperiod (hrs dark / hrs light): 12/12

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: glass and acrylic chamber with an acrylic antechamber
- Exposure chamber volume: 0.152 m³
- Source and rate of air: airflow was 31 L/min
- Method of conditioning air: The vapor exposure atmosphere was generated using an in-house designed vapor exposure chamber with a glass bead-column generation system. The vapor generation system operated as follows: Test article was delivered from a 50 mL gas-tight syringe through 1/8" Teflona tubing by a syringe pump at a constant rate of approximately 59 µL/min (198 ppm group) and 464 - 580 µL/min (2312 ppm group) to a chromatography column containing glass beads. For the 4731 ppm group, a digital FMI pump was used instead of a syringe pump. The FMI pump was calibrated to determine the appropriate setting for the required flow rate. Compressed air, metered by a flowmeter at approximately 15 L/min, flowed counter current, vaporizing the test article. Concentrated vapors of the test article were diluted with additional compressed air to achieve the desired concentration. The dilution air was metered with a flowmeter at the rate of 16 L/min. The test article vapor laden air stream was then delivered to the exposure chamber through a stainless steel "T" to aid chamber distribution.
- Treatment of exhaust air: Prior to the exposure, samples were taken from the animal breathing zone of the chamber to show that the test article was evenly distributed. Samples taken from the exposure chamber were analyzed during a test trial prior to the initial Group 1 animal exposure.
- Temperature, humidity, air chamber: 21 °C, 28 - 42% (test chamber)

TEST ATMOSPHERE
- Samples taken from breathing zone: yes
- Brief description of analytical method used: A Miran infrared (IR) spectrometer monitored the chamber atmosphere for Y-1205. The IR was used to continuously monitor chamber concentrations and make real-time adjustments during the exposures. Atmosphere samples were drawn into the IR at a constant rate from the breathing zone of the animals. The IR response was displayed on a multimeter and recorded at approximately hourly intervals. Test article chamber levels were determined from a calibration curve. In addition, samples of the Y-1205 exposure atmospheres were collected hourly and analyzed using the Sponsor-supplied gas chromatography (GC) method. Samples were collected approximately once per hour during the exposures. Actual chamber concentration of Y-1205 and ethanol were determined by GC. Because ethanol is a hydrolysis product of Y-1205, GC analysis of ethanol in the chamber atmosphere provided an indication of the exposure atmosphere integrity (a stable, non-fluctuating atmosphere during exposure duration) and the test article hydrolysis. Purity analysis was conducted on the neat test article collected before each exposure to ensure purity was 92% or higher.

CLASS METHOD
- Rationale for the selection of the starting concentration: The exposure levels were selected by the Sponsor, or in consultation with the Sponsor, on the basis of available data from previous studies with structurally analogous materials.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(GC)

Duration of exposure:

4 h

Concentrations:

337, 2688 and 8091 ppm (males/females, nominal concentration)
198, 2312 and 4731 ppm (males/females, analytical concentration)
1.10, 12.90 and 26.4 mg/L (males/females, calculated analytical concentration at 20°C using a MW of 134.25 g/mol)

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: All animals received a detailed clinical examination just prior to exposure, immediately upon removal from the chamber, at 1,2, and 4 hours post-exposure, and once daily thereafter. All rats received an ophthalmoscopic examination prior to exposure and within 60 minutes post-exposure. Neurobehavioral observations were conducted once daily on days 2 - 15. Body weight measurements were measured and recorded just prior to exposure on day 1 and on days 2, 3, 5, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: All major organs in the thoracic and abdominal cavities were observed for gross abnormalities, all gross lesions were saved, and the carcasses were discarded.

Statistics:

The means and standard deviations were calculated for body weights.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

26.4 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: calculated analytical concentration using at 20°C using a MW of 134.25 g/mol

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

4 731 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred in the groups exposed to 198 ppm and 2312 ppm Y-1205 vapors. The mortality for animals exposed to 4731 ppm Y-1205 vapors was 50% (2 males, 3 females).

Clinical signs:

other: Test article-related clinical signs observed during all the exposures included decreased activity and body surface staining. Signs of toxicity observed post-exposure and during the 14 day observation period for the 2312 ppm groups were hair loss, body sur

Body weight:

Group mean body weights were moderately affected by exposure to Y-1205. In general, surviving animals lost weight immediately post-exposure, then gained weight to exceed their pre-exposure weight by the end of the 14 day observation period.

Gross pathology:

There were no organ specific test article-related macroscopic observations noted in these animals. One 4731 ppm male rat that died on study was thin, indicating that the animal was not eating and simply confirming the systemic toxicity induced by the compound. Also, a single 4731 ppm female that died on study was noted to have red discoloration of the lungs. This is a common finding in animals found dead on study. Since this finding was only noted in 1 high dose animal, it is doubtful that this represents a test article-induced lesion. The small testis and epididymis noted at 4731 ppm occurred in the same male rat and only the left testis and epididymis were affected. These findings, and the pelvic dilatation in the kidney, are commonly occurring lesions in rats of this age and strain and are not considered to be test article-related.

Other findings:

No ophthalmoscopic abnormalities were observed in the rats exposed to 198 or 2312 ppm of Y-1205. The rats exposed to 4731 ppm of Y-1205 were normal prior to exposure and 9 of the 10 rats had pupillary constriction (pinpoint miosis) post-exposure.

Any other information on results incl. tables

Table 1: Mortality data

Cumulative Group Mortality data
Group	Number of animals (M/F)	Day death occurred						Cumulative Mortality
		1		4		9		Males	Females	Combined
		M	F	M	F	M	F
1	5/5	0	0	0	0	0	0	0	0	0
3	5/5	0	0	0	0	0	0	0	0	0
4	5/5	0	3	1	0	1	0	2	3	5

M= males

F= females

Group 1: 198 ppm, group 3: 2312 ppm, group 4: 4731 ppm

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 conclusion, under the conditions of the present study conducted in manner similar to OECD 403 and GLP, the LC50 is > 26.4 mg/L for both male and female rats. The test substance does not need to be classified for acute inhalation toxicity.