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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13.02.96 to 14.02.00
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:
1999
Report date:
2000

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chlorotrimethylsilane
EC Number:
200-900-5
EC Name:
Chlorotrimethylsilane
Cas Number:
75-77-4
Molecular formula:
C3H9ClSi
IUPAC Name:
chloro(trimethyl)silane

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age:  Approximately eight weeks, weighing 183 +/- 31 grams (males) and 141  +/- 12 grams (females) when exposed.
TEST ANIMALS
- Source: Raleigh, North Carolina.
- Age at study initiation: Approximately seven weeks when received.
- Weight at study initiation: Males: 129.1-152.0 g. Females: 152.4-212.2 g.
- Fasting period before study: No data
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven 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: 20.05.98 To: 12.06.98

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Trimethylchlorosilane was introduced into a heated stainless steel J-tube containing a column of stainless steel ball bearings at a controlled rate utilising a FMI pump. Nitrogen, passing through the J-tube at a rate of 8 lpm, served as a carrier gas for vapour generation and transfer of trimethylchlorosilane vapour from the vapour generator to the exposure chamber. Nitrogen was selected for use as an inert carrier gas because of the potential hazards associated with the generation of vapour concentrations above the lower flammability limit for trimethylchlorosilane.
- Exposure apparatus: Wire mesh cages specifically designed for use in the exposure chamber. The exposure caging was circular in shape and divided into ten equal sized triangular-shaped compartments.
- Exposure chamber volume: 175 l
- Method of holding animals in test chamber: The animals were placed into exposure cage compartments, one rat per compartment, arranged in a "staggered by sex" configuration around the exposure caging.
- Source and rate of air: No data
- Method of conditioning air: No data
- Treatment of exhaust air: No data
- Temperature, humidity in air chamber: 23.6-24.6oC and 35.5-38.8%


TEST ATMOSPHERE
- Brief description of analytical method used: Analysis of the chamber atmosphere and trimethylchlorosilane vapour/nitrogen gas carrier stream from the vapour generation system was performed with a Gas Chromatograph utilising both a Thermoconductivity Detector and a Mass Selective Detector.
- Samples taken from breathing zone: yes, trimethylchlorosilane was sampled three times during the course of each exposure period.



Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
1 h
Concentrations:
3171, 4139, 4268 and 5121 ppm (nominal).
918, 1431, 1624 and 1666 ppm (actual)
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
Post dose observation period:  14 days
Exposure duration (for inhalation studies):  One hour (after equilibration, T90 = 6 minutes) using whole body exposure methods
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations immediately after exposure and then daily for 14 days. Body weights were recorded on the day of randomisation and study days 1, 8 and 15.
- Necropsy of survivors performed: yes, on Day 15
- Other examinations performed: Gross examination.
Statistics:
LC50 determined using Spearman-Karber analysis

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4 257 ppm
95% CL:
4 039 - 4 488
Exp. duration:
1 h
Mortality:
See table below
Clinical signs:
other: The principal clinical signs were indicative of  respiratory and ocular effects.  Labored breathing, rales and gasping  were seen in essentially all rats, most frequently early in the study  period.  Some signs of respiratory distress persisted well into 
Body weight:
Body weight loss was apparent in all exposure groups. Recovery of body mass was common in animals that survived to Day 15.
Gross pathology:
Lung and evidence of upper respiratory tract injury were predominant features observed at necropsy.  In general, this consisted of pulmonary consolidation, congestion and/or hemorrhage in  rats that died and ectasia and atelectasis in many of the rats that survived to the scheduled necropsy.  A number of rats also exhibited  corneal opacity, which was considered to be a direct result of exposure  to the test article under the conditions of this study.
Other findings:
Potential target organs:  Respiratory tract (nares and lungs) and eyes (corneas)

Any other information on results incl. tables

Number of deaths at each dose level:

Sex

Dose level (ppm)

No. Deaths

Days to Death

Males

3171

0/5

NA

4139

2/5

3,3

4268

3/5

2,3,4

5121

5/5

3,3,3,3,4

Females

3171

0/5

N/A

4139

0/5

N/A

4268

3/5

2,3,4

5121

5/5

3,3,4,4,4

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a good quality (reliability score 1) acute inhalation study conducted according to OECD test guideline 403, the acute one-hour LC50 , based on nominal concentrations, was determined to be 4257 ppm (nominal).
Executive summary:

Four groups of Fischer 344 rats (5/sex) were exposed by whole-body vapour inhalation to trimethylchlorosilane vapour for one hour followed by a 14 day observation period. Gross necropsies were performed on all animals. The nominal exposure levels were 3171, 4139, 4268 and 5121 ppm. The mortality observed was 0, 2 (males), 6 (3/sex) and 10 (5/sex), respectively. Deaths occurred 2 -4 days after the exposure period. Clinical signs of toxicity were indicative of respiratory (rales, gasping, nasal fluid discharge), and ocular (corneal opacities, lacrimation) effects. In animals that died lung injury was a predominant adverse effect. The LD50 was calculated to be 4257 ppm (nominal).

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