2,11-Dioxa-3,10-disiladodecane, 3,3,10,10-tetramethoxy-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1993-01-20 to 1993-02-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted according to the appropriate OECD test guideline and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Remarks:

no significant deviations

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

87135-01-1

Molecular formula:

C12H30O6Si2

Constituent 2

Reference substance name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

EC Number:

617-969-6

Cas Number:

87135-01-1

Molecular formula:

(CH3O)3Si(CH2)6Si(OCH3)3 C12 H30 O6 Si2

IUPAC Name:

3,3,10,10-tetramethoxy-2,11-dioxa-3,10-disiladodecane

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River breeding labs (no further details)
- Age at study initiation: 6-9 wk
- Weight at study initiation: 155-205 g
- Fasting period before study: fasting during exposure
- Housing: 1/stainless steel cage with wire mesh bottom
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 50 +/-20
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/ 12h

IN-LIFE DATES: From: 1993-01-20 To: 1993-02-03

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: 450 litre stainless steel and glass exposure chamber.
- Method of holding animals in test chamber: none stated.
- Source and rate of air: the chamber was operated under dynamic conditions; chamber air was ambient air which had been filtered (hepa and charcoal filters); airflow through the chamber was approximately 12-15 air changes/h.
- Method of conditioning air: the test material was introduced into the chamber though a specially designed glass J-tube. The material was metered into the J-tube with a Harvard Apparatus syringe pump. Instrument air was filtered with a Matheson filter and dried with a Zeks Air Drier, Model 24HSBA100, then introduced into the J-tube at a controlled rate. Glass beads in the J-tube and heating tape (temperature of the air in J-tube was approximately 65°C) were used to help vaporize the test material. The test material was then passed into the inlet port at the top of the chamber.
- Method of particle size determination: n/a
- Treatment of exhaust air: the exhaust air was filtered by hepa and charcoal filters and then passed through a water cyclone before being exhausted through the roof of the building.
- Temperature, humidity, pressure in air chamber: chamber temperature, relative humidity, and airflow measurements were recorded every five minutes during the exposure period with the Camile8 Data Acquisition System. Temperature and humidity in the chamber was kept in the range of 23-28°C and 25-42% relative humidity, respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: none during study
- Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

no

Remarks:

nominal concentration determined from weight measurements

Duration of exposure:

4 h

Concentrations:

Male and female rats were exposed to a target concentration of 0.033 mg/L (2.5 ppm) for 4h. Measured target concentration was 0.042 mg/l.

The saturated vapour concentration of the test material at room temperature is approximately 5.0 ppm. The target concentration of 2.5 ppm was considered the highest concentration that could be reasonably produced given the test generating equipment and exposure chamber.

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: animals were observed daily during the 14-day post­ exposure period for mortality or overt signs of toxicity. Each animal was examined daily during weekdays for any treatment related effects including any evidence of respiratory, dermal, behavioural, nasal or ocular changes suggestive of local irritancy of the test material.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (see above), body weight (Individual body weights of animals were determined prior to exposure, and on days 8 and 15 of the study), organ weights (no), histopathology (no).

Statistics:

Prior to exposure, animals were weighed and those within the acceptable weight range were randomized by the AESLECT program of the Xybion TOX/PATH System and assigned to the exposure group. No further details.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.042 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: The test concentration was considered the highest that could be reasonably produced given the test generating equipment and exposure chamber.

Mortality:

No deaths (see table 1,below).

Clinical signs:

other: No clinical signs (see table 1,below).

Body weight:

There were no apparent effects on body weight gains or food consumption. (The appendix containing these data was not included in the 10 pages of this report that were presented and have been reviewed.)

Gross pathology:

Gross pathologic examination of the animals during terminal sacrifice did not reveal any evidence of test article-related tissue change in males and four of the five female animals. One female animal exhibited a slightly enlarged thymus with multiple red foci. The significance of this finding in one out of ten exposed animals is unknown at this time.

Any other information on results incl. tables

Table 1: Concentration, mortality, evident toxicity

Nominal Concentration by weight (mg/l)	Mortality male	Mortality female	Number with evident toxicity (males and females/total))	Summary of necropsy findings
0.042	0/5	0/5	0/10	1/10*

* 1 female with thymus enlarged and with multiple red foci

Applicant's summary and conclusion

Interpretation of results:

other: exposure concentration too low to classify

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A reliable study conducted in compliance with the standard guideline of the time and in accordance with GLP, found the 4-h LC50 to be greater than 0.042 mg/l in male and female rats.