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Administrative data

Description of key information

In the key acute oral toxicity study, conducted according to OECD 401 and in compliance with GLP, the LD50 for male and female rats was >2000 mg/kg (Huls, 1998). Clinical symptoms were noticed 30 minutes to six hours after treatment. Abnormal gait, squatting position, sedation, paddling movements, piloerection, diarrhoea and diuresis were observed. From day one until the end of the study (day 14) no other clinical signs were observed. No abnormalities were detected at necropsy.

In the acute inhalation study, conducted in accordance with OECD 403 and in compliance with GLP, the LC50 was determined to be >21.3 mg/l in male and female rats (Muijer, 1998). There were no mortalities or clinical signs of toxicity. Findings at necropsy consisted of abnormalities in the lungs, intestines and testes. Abnormalities of the lungs consisted of petechiae and/or hyalin spots or areas on one or more lobes in most animals. Pale discolouration of the lungs was seen in one male animal.

In the key acute dermal toxicity study, conducted according to OECD 402 and in compliance with GLP, the LD50 for male and female rats was determined to be >2000 mg/kg. (Huls, 1998). There were no clinical signs, signs of local irritation or abnormalities at necropsy.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998/01/26-1998/02/12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
There were no deviations from the protocol.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HsdCpb:WU/SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, 33176 Borchen

- Age at study initiation: young adults

- Weight at study initiation: per sex the weight variation did not exceed +/- 20% of the mean body weight

- Fasting period before study: 16 hours

- Housing: Makrolon type 3 cages, group-caged by sex, each cage containing max. five rats

- Diet: Ssniff R 10 diet in pellete form, ad libitum, except that animals were fasted prior to substance administration for a period of about 16 hours. 3 hours after application food was offered ad libitum.

- Water: tap water, ad libitum

- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 +/- 3

- Humidity (%): 30-70%

- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.11 cm3/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: in the first step three male rats were given a single oral application of the test substance at a limit dose of 2000 mg/kg bw. SInce no mortalities occurred within 24 hours p.a., three female rats were treated the same way.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3M, 3F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Rats were checked at least twice daily for any mortalities. Animals were observed soon after dosing and at frequent intervals for the remainder of the day of dosing (ca. 6 hours). On subsequent days animals were observed once a day. The nature and severity of the clinical signs and time were recorded at each observation. Individual bodyweights were recorded on days 0 (prior to dosing), 7 and 14.

- Necropsy of survivors performed: yes, animals were killed on day 14 by CO2 inhalation

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All animals were subjected to macroscopic examination after opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded for each animal.
Statistics:
No statistical analysis was carried out.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities in response to exposure.
Clinical signs:
Clinical symptoms were noticed 30 minutes to six hours after treatment. Abnormal gait, squatting position, sedation, paddling movements, piloerection, diarrhea and diuresis were observed. From day one until the end of the study (day 14) no other clinical signs were observed.
Body weight:
All animals achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
The macroscopic examination revealed no abnormalities.
Other findings:
No other findings reported.

The oral LD50 value of tetramethylsilane was found to be >2000 mg/kg for male and female rats.

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified according to Regulation (EC) No 1272/2008
Conclusions:
The oral LD50 value of tetramethylsilane was found to be >2000 mg/kg for male and female rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998/09/25-1998/10/09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
other: EEC Directive 92/69/EEC, Annex, Part B
Principles of method if other than guideline:
The dewpoint of the dry pressuirzed air was below -65C and relative humidity was intentionally kept as low as possible. Oxygen concentration and relative humidity were not measured, because of expected damage to the apparatus used by the high tetramethylsilane concentration. Relative humidity was above 70% (up to 74%) for at most 4 hours on 2 days outside the exposure period. During the 4 hour exposure period, generation was intermitted three times for 1 minute to allow exchange of the Tedlar bags. The time lost was compensated by extending the exposure period by 3 minutes. The deviations from the protocol were not considered to have influenced the validity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Wistar (Crl:[WI]WU BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Charles River Wiga, Suzfeld, Germany

- Age at study initiation: ca. 5-6 weeks

- Weight at study initiation: mean weights 316g males, and 196g females

- Fasting period before study: Not specified, but animals had no access to feed or water during the exposure period

- Housing:During exposure animals were housed individually in their holders, which after they were returned to their living cages, 5 males or 5 females to a suspended stainless steel cage, fitted with wire-mesh floor and front.

- Diet: Commercially available rodent diet (Rat & Mouse No.3 Breeding Diet RM3) from SDS Special Diets Services, Witham, England, ad libitum

- Water: Tap water suitable for human consumption (quality guidelines according to Dutch legislation based on EEC Council Directive 80/778/EEC), ad libitum



ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19.5-21

- Humidity (%): between 46-74

- Air changes (per hr): ca.10

- Photoperiod (hrs dark / hrs light): 12/12


Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: A nose only exposure chamber, to which a gas mixture was drawn from the Tedlar bags via a rotameter using the suction of a compressed air-driven nebulizer put on as a pump.

- Method of holding animals in test chamber: in animal holders

- Source and rate of air: The air flow through the exposure chamber was 24 litres/min during exposure. The setting of the input pressure of the nebulizer was recorded at regular intervals (approximately each half hour) during the generation of the test atmosphere the Tedlar bags were exchanged about every hour and were weighted before and after each period of use. In this way the stability of the generation could be estimated. Since generation was intermitted three times for 1 minute to allow exchange of the tedlar bags, the time lost was compensated by extending the exposure period by 3 minutes. Before exposure, the air consumption of the nebulizer was established for a range of input pressures and although the relation was roughly linear, a more accurate fit could be obtained by using the fine tuning offered by a third order polynomial.

- Method of conditioning air: The inhalation equipment was designed to expose rats to a continuous supply of fresh test atmosphere. The test atmosphere was generated as follows: First, two tedlar bags were each filled with 29 l dry pressurized air and subsequently with 103.2 grams of the test material fluid form which was allowed to evaporate. The air was added to dilute the vapour of the test material and thereby preventing condensation. Subsequently, the gas mixture was drawn alternately from the Tedlar bags to the inhalation chamber via a rotameter using the suction of a compressed air-driven nebulizer put on as a pump. In this way a small stream of test material vapour was mixed with the compressed air consumer by the nebulizer.The nebulizer was placed at the top inlet of the exposure unit. From there, the test atmosphere moved downward towards the animal noses. At the bottom of the unit the test atmosphere was exhausted.


- Temperature, humidity, pressure in air chamber: The temperature was recorded nine times during exposure at regular intervals using a glass/mercury thermometer. Relative humidity was not measured, because it was expected that the test material would damage the probe of the device used for measurement of relative humidity. For the same reason, oxygen concentration was not checked during exposure.


TEST ATMOSPHERE

- Brief description of analytical method used: The actual concentration of vapours is virtually identical to the nominal concentration. Thus the actual concetration was derived from the nominal concentration. The nominal concentration was calculated by carefully weighing the Tedlar bag filled with a mixture of test material and air before and after the experiment. Mean concentrations for each for hour exposure were derived by calculating the weight loss of the Tedlar bags during exposure. The value obtained was corrected to 21.3+/- 1.5g/m3, because of the contribution of the flow containing the test material to the volume of the total airflow.





Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
21.3 g/m3 +/- 1.5
No. of animals per sex per dose:
5M/5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure and at least once daily during the observation period. Body weights were recorded just prior to exposure (day 0) and on days 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: All rats were killed by exsanguination from the abdominal aorta under anasthesia. All rats were necropsied and examined for gross pathological changes.
Statistics:
The mean and standard deviation of tetramethylsilane in the test atmosphere were calculated and corrected to -1% to account for the airflow.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21.3 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: No abnormalities were observed in the animals during the exposure or during the observation period.
Body weight:
Mean overall body weight gain was generally considered to be within the normal range.
Gross pathology:
Findings at necropsy consisted of abnormalities in the lungs, intestines and testes. Abnormalities of the lungs consisted of petechiae and/or hyalin spots or areas on one or more lobes in most animals. Pale discolouration of the lungs was seen in one male animal.
Other findings:
- Potential target organs: lungs and intestines

- Other observations: The tense intestines in 3 male and 1 female animal were remarkable also. Although seldom seen, the relation with exposure is not obvious, but cannot be excluded however. Cryptorchidism as present in 3 out of 5 males cannot be related to exposure in males this age.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute inhalation LC50 value of >21.3 mg/l in rats was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
21 300 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998/04/28-1998/05/12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (No L383A) Part B, Appendix B. 3., Acute Toxicity (dermal)
Principles of method if other than guideline:
There were no deviations from the protocol.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar (Hsd/Win:WU/SPF
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Harlan Winkelmann GmbH, Gartenstrasse 27, 33176, Borchen

- Weight at study initiation: 200-300g

- Fasting period before study:

- Housing: Makrolon Type 3 caages, each containing one rat. The bedding used was soft wood Type HW 300/500 W, produced by JELU-WERK, Ludwigsmuhle, 73494 Rosenberg.

- Diet: Ssniff R 10 diet in pellet form (laboratory standard rat diet), ad libitum, produced by Ssniff Spezialfutter GmbH, 59494 Soest

- Water: Tap water, ad libitum

- Acclimation period: Minimum of 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22 +/- 3

- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal rooms

- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE

- Area of exposure: dorsolumbar region

- % coverage: 10

- Type of wrap if used: gauze, held in place with a semiocclusive dressing encircled firmly around the trunk


REMOVAL OF TEST SUBSTANCE

- Washing (if done): the treated area was cleaned with corn oil and absorbent paper

- Time after start of exposure: 24 hours


TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 3.11 cm3/kg bw

- Concentration (if solution): undiluted

- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5M/5F
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed ca. 30 minutes after dosing and at hourly intervals for the remainder of day 0 ( period of ca 6 hours). On the following 14 days animals were observed once daily and the nature of clinical signs observed were recorded at each observation.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The rats were checked at least twice daily for any mortalities. Thedermal response was observed once a day 24 h p.a. the first time and 14 days p.a. the last ti me. local dermal irritations as well as any other lesions were recorded. All animals were killed on day 14 by CO2 inhalation and subjected to macroscopic examination after opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded for each animal.
Statistics:
No statistical analysis was carried out.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no signs of systemic reaction to treatment.
Clinical signs:
After removal of the dressings 24 hours post application, until the end of the study no skin irritation was observed.
Body weight:
The male rats achieved satisfactory bodyweight gains throughout the study. Two female rats showed minimal bodyweight gain after the first week and one female rat after the second week. At the end of the study four female rats achieved satisfactory bodyweight gains. Variation of bodyweight in this age/bodyweight range is a physiological finding and not substance related.
Gross pathology:
The macroscopic examination on day 14 revealed no abnormalities.
Other findings:
No other findings reported.

The acute lethal dermal dose to rats of tetramethylsilane was found to be greater than 2000 mg/kg bw.

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal LD50 value of >2000 mg/kg bw in rats was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The key acute oral and dermal toxicity studies (Huls, 1998a and Huls, 1998b) were the only available data for those endpoints. The studies were conducted in accordance with appropriate OECD test guidelines and in compliance with GLP, and were therefore assigned Reliability 1.

The key acute inhalation toxicity study (Muijer, 1998) was selected as the most reliable study available for this endpoint. It was conducted according to OECD 403 and in compliance with GLP, and was therefore assigned Reliability 1. An additional non-standard inhalation study is available in which the exposure duration was only 30 minutes.

Justification for classification or non-classification

Based on reliable measured data for the oral, inhalation and dermal routes, tetramethylsilane is not classified for acute toxicity according to Regulation (EC) No 1272/2008.