Registration Dossier

Administrative data

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:
other: The 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:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Wistar (Crl:[WI]WU BR)
Sex:
male/female
Details on test animals 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


Administration / exposure

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.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21.3 mg/L air
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
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.