Tetramethylsilane

Endpoint summary

Description of key information

A combined repeat dose inhalation toxicity study and reproductive/developmental toxicity screening study was carried out for tetramethylsilane according to OECD 422 and in compliance with GLP (DCC, 2005). There were no adverse effects on general systemic, reproductive or developmental endpoints at the highest dose tested, 5000 ppm (ca. 18,000 mg/m3).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Remarks:

combined repeated dose and reproduction / developmental screening

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

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

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation 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.

Duration of treatment / exposure:

6 hours/day 7 days/week
Males: 29 days (including 14 days premating).
Females: 14 days premating, through mating, gestation and up to day for postpartum.
Females, toxicity group: 28 days

Frequency of treatment:

Daily

Dose / conc.:

200 ppm

Remarks:

target concentration

Dose / conc.:

1 000 ppm

Remarks:

target concentration

Dose / conc.:

5 000 ppm

Remarks:

target concentration

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Dose selection rationale: Based on results of a dose range finding study.
- Rationale for animal assignment (if not random): Random
- Rationale for selecting satellite groups: Toxicity group females to assess toxicity without pregnancy.
- Post-exposure recovery period in satellite groups: None

Positive control:

None

Observations and examinations performed and frequency:

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


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: On the day of sacrifice.
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes, overnight
- How many animals: All males and toxicity group females.
- Parameters checked in table No.1 were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On the day of sacrifice.
- Animals fasted: Yes
- How many animals: All males and toxicity group females.
- Parameters checked in table No.1 were examined.


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Prior to the start of exposure and during the fourth week of exposure.
- Dose groups that were examined: all males and toxicity phase females.
- Battery of functions tested: cageside observations, hand-held observations, open field observations, categorical observations, measurements/counts, motor activity.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2) for 10 animals/sex from the toxicity groups.

Other examinations:

None

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.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY: there were no deaths or treatment-related clinical signs of toxicity.


BODY WEIGHT AND WEIGHT GAIN: statistically significant increase in body weight gains observed during week four of toxicity group females. No other significant finding.


FOOD CONSUMPTION: No significant findings.


HAEMATOLOGY: In males, slight but statistically significant decreases in percent monocytes were noted in 1000 and 5000 ppm groups. However, the decrease was not considered to be of toxicological significance because the values were within the laboratory historical controls.


CLINICAL CHEMISTRY: In females there were statistically significant decreases in chloride levels in the 1000 and 5000 ppm exposure groups. The slight decreases were not considered treatment-related because they were within the range typical of this strain and age.


NEUROBEHAVIOUR: No adverse effects in males. A slight but statistically significant (p<0.02), decrease was noted in the female 200 and 1000 ppm exposure groups compared to the control group, in which a slight increase was noted. There were no other findings.


ORGAN WEIGHTS: Slight but statistically significant increase in mean spleen weights was observed in the 5000 ppm group females. There was no correlation with histopathological changes.


GROSS PATHOLOGY: No adverse findings.


HISTOPATHOLOGY: There were no findings clearly attributable to treatment. There were some minor, adaptive changes in the liver.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 5 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed

Critical effects observed:

no

Conclusions:

In an inhalation OECD 422 study conducted to GLP (reliability score 1) the NOAEL for systemic toxicity of the adult rats was at least 5000 ppm (the highest concentration tested).

Executive summary:

In an inhalation OECD 422 study conducted to GLP (reliability score 1) the NOAEL for systemic toxicity of the adult rats was at least 5000 ppm (the highest concentration tested).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

18 000 mg/m³

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for repeated dose toxicity is the only available study for this endpoint. The study was conducted in accordance with an appropriate OECD test guideline and in compliance with GLP, and was therefore assigned Reliability 1. A range-finding study is also available.

Justification for classification or non-classification

There are no data to suggest that tetramethylsilane should be classified for specific target organ toxicity following repeated exposure according to Regulation (EC) No 1272/2008.

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