Tetramethylsilane

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02.12.2003 to 27.05.2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD guideline 422

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylsilane

EC Number:

200-899-1

EC Name:

Tetramethylsilane

Cas Number:

75-76-3

Molecular formula:

C4H12Si

IUPAC Name:

tetramethylsilane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc.
- Age at study initiation: 9 weeks minimum
- Weight at study initiation: Males: 289.6 to 339.7 g; females: 183.3 to 244.1 g.
- Fasting period before study: No
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Six days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 64-79
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.04.2004 To: 09.08.2004

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2000 l stainless steel and glass Rochester-style inhalation chambers.
- Method of holding animals in test chamber: stainless steel exposure caging (four layers of 20 animal compartments).
- Source and rate of air: Room air
- Method of conditioning air: Air passed through HEPA and activated charcoal filters before delivery to the chamber. Moisture was added to maintain relative humidity.
- System of generating particulates/aerosols: Not applicable
- Temperature, humidity, pressure in air chamber: 22±3oC, 50±20%,
- Air flow rate: No data
- Air change rate: 10-15 air changes/hour
- Method of particle size determination: Not applicable.
- Treatment of exhaust air: No data


TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatograph with flame ionisation detection
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The test atmosphere from each chamber was sampled by an automated sampling system. The test atmosphere was continuously pulled from the chamber and delivered to the analyser. Analysis was by gas chromatograph with flame ionisation detection (GC/FID) and each chamber was evaluated at least once per hour during the exposure period.

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: Continuous until proof of mating.
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy.
- Further matings after two unsuccessful attempts: No
- After successful mating each pregnant female was caged (how): Individually in home cage.

Duration of treatment / exposure:

6 hours/day
Males: 29 days (including 14 days premating).
Females, reproductive group: 14 days premating, through mating, to gestation day 19 (termination day four postpartum).
Females, toxicity group: 28 days

Frequency of treatment:

Daily

Duration of test:

approximately 46 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

200 ppm

Remarks:

target concentration

Doses / concentrations 2

Dose / conc.:

1 000 ppm

Remarks:

target concentration

Doses / concentrations 3

Dose / conc.:

2 000 ppm

Remarks:

target concentration

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Dose selection rationale: Based on the results of a range-finding study.
- Rationale for animal assignment (if not random): Random

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Mortality, morbidity and moribundity noted at least twice daily (all animals). Clinical observations made once per day (all animals).


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once before the first exposure, and weekly thereafter (all animals).


BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were determined before the first exposure and at least weekly thereafter, and the day of necropsy. Pregnant females were weighed on gestation days 0, 7, 14 and 20, within 24 hours after parturition, and on day 4 postpartum.


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data

Fetal examinations:

- External examinations: Yes, all per litter
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No

Statistics:

All data analysis was conducted using SAS version 8.2. Statistically significant probabilities were reported for p-values of <0.05, 0.02 and 0.01.

Indices:

Mean gestation length, mean number of implantation sites, mean number of corpora lutea, mean mating and fertility indices. Mean litter size, mean live litter size, mean litter weight, mean ratio live births/litter size.

Historical control data:

No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
There was no significant toxicity in dams.

Effect levels (maternal animals)

1

Key result

Dose descriptor:

NOAEL

Effect level:

>= 5 000 ppm

Basis for effect level:

other: maternal toxicity

2

Key result

Dose descriptor:

NOAEL

Effect level:

>= 5 000 ppm

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no adverse effects on the offspring.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 5 000 ppm

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In an inhalation OECD 422 study conducted to GLP (reliability score 1) the NOAELs for general systemic toxicity of the dams and developmental toxicity were both at least 5000 ppm (the highest concentration tested) in rats.

Executive summary:

In an inhalation OECD 422 study conducted to GLP (reliability score 1) the NOAELs for general systemic toxicity of the dams and developmental toxicity were both at least 5000 ppm (the highest concentration tested) in rats.