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Toxicological information

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:
1996/05/31-1997/07/08
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:
1997
Report date:
1997

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:
Trichloro(ethyl)silane
EC Number:
204-072-6
EC Name:
Trichloro(ethyl)silane
Cas Number:
115-21-9
Molecular formula:
C2H5Cl3Si
IUPAC Name:
trichloro(ethyl)silane
Details on test material:
- Name of test material (as cited in study report): DOW CORNING 1-2252 (Ethyltrichlorosilane)

- Substance type: CHLORO-Si (TRI-Cl)

- Lot/batch No.: BC056016

- Stability under test conditions: Stable in inert atmosphere.

- Storage condition of test material: Stored in a closed container in a ventilated chlorosilane storage cabinet.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Age at study initiation: ca. 6-7 weeks

- Weight at study initiation: 80-100g

- Fasting period before study: Not described.

- Housing: At arrival the animals were placed in individually, sequentially numbered cages. The cages were made of stainless steel with wire mesh bottoms.

- Diet: Certified Rodent Chow ad libitum, except during exposure

- Water: ad libitum, except during exposure

- Acclimation period: The animals were quarantined for one week prior to initiation of study.


ENVIRONMENTAL CONDITIONS

- Temperature: 65-78F (18-26 °C)

- Humidity (%): 40-70

- Air changes (per hr): 10-15

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


IN-LIFE DATES: Not stated.

Administration / exposure

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: PVC and plexiglass whole body chamber

- Exposure chamber volume: 175 litres

- Method of holding animals in test chamber: Animals were contained in the chamber.

- Source and rate of air: The air was supplied by a Nash compressor and filtered with a series of Balston filters. Airflow through the chamber was approximately 45 air changes per hour.

- Method of conditioning air: Dry air flowed through at a controlled rate and the air/vapour mixture passed into the inlet port at the top of the chamber where it was mixed with chamber supply air prior to induction into the chamber.


- Temperature, humidity, pressure in air chamber: A chamber leak test was performed before the start of the study and the chamber was operated under slight negative pressure (~0.6"H2O) to prevent contamination of the work place in case of leaks developing in the system.

-Exposure duration:  One hour plus six minutes (T99) 

TEST ATMOSPHERE

- Brief description of analytical method used: The efficiency of the test article generation system was monitored by measuring the chloride ion concentration at the end of the delivery system from the J-tube with an electrolytic conductivity detector and comparing the result with the chloride ion concentration calculated for the nominal concentration of the test article. A Hewlett Packard 5890 gas chromatograph (GC)/5972 mass spectometer (MS) was used to monitor the test article concentration in the chamber and provide mass spectroscopy analysis of the chamber atmosphere.

- Samples taken from breathing zone: yes, a minimum of three samples were collected for test article analysis during each exposure.




Analytical verification of test atmosphere concentrations:
yes
Remarks:
GM/MS
Duration of exposure:
1 h
Concentrations:
1415, 1156, 1326 ppm (nominal exposure concentration). 691, 537 and 605 ppm (mean test article chamber concentration). The nominal concentration results were significantly higher than the actual concentration results due to the reactivity/hydrolysis of the test article.
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Individual body weights were collected for randomisation purposes prior to exposure. Body weights were also collected on days 1,8 and 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: All surviving rats were observed immediately following exposure and once a day for 14 days following exposure for treatment related signs of toxicity. Signs included but were not limited to any evidence of respiratory, behavioural, nasal and/or ocular changes. Mortality/morbidity check was performed twice daily on weekdays, once a day on holidays/weekends.
Statistics:
The inhalation median lethal concentration (LC50), 95% fiducial limits and approximate slope of the dose curve were calculated using SAS/STAT Probit procedure. Body weight means and standard deviation were also calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 257 ppm
95% CL:
> 1 175 - < 1 320
Exp. duration:
1 h
Mortality:
All animals exposed to the 1415 ppm died during the 14 day observation period with majority dying by study day 3. Two animals (1M, 1F) exposed to 1156 ppm died by study day 5. Six animals (4M, 2F) exposed to 1326 ppm died by study day 3.
Clinical signs:
other: Description, severity, time of onset and duration of clinical signs at each dose level:  Respiratory (labored breathing, rales),  activity (hypoactivity, ataxia) and ocular (closed eyes, lacrimation, porphyrin staining, corneal opacity, dried material and
Body weight:
All surviving animals exposed to 1156 and 1326 ppm gained weight by the end of 14 day observation period. However, mean body weights for surviving females exposed to 1156 ppm and for surviving males and females exposed to 1326 ppm were slightly depressed at the end of the first week.
Gross pathology:
Necropsy findings, included doses affected, severity and number of animals affected:  There were no remarkable gross findings
in rats that survived to the scheduled necropsy.  Frequently noted necropsy findings in the 18 rats that died (all groups) 
included ectasia of the lungs (13), obstruction of the nostrils (13), staining, fluid and/or crusts on the nares (13), dark 
red/congested livers (10), hemorrhage, congestion and/or consolidation of the lungs (3) and discoloration or staining 
of the fur (18).  Other findings in rats that died included blood in the GI tract (9), gaseous distention of the GI tract (3), 
corneal opacity (5), dehydration (4) and a decrease or absence of body fat (2).
Other findings:
Potential target organs (if identified in the report):  Eyes and lungs
If both sexes tested, results should be compared:  Responses between males and females were generally consistent

Any other information on results incl. tables

Table 1: Concentrations, exposure conditions and number of evident toxicity per animals treated

Nominal Conc.(ppm)

Analytical Conc.(ppm)

Number with evident toxicity (#/total)

Males

Females

Combined

 1415

 691

 5/5

5/5

10 

 1156

 537

 1/5

1/5 

 2

 1326

 605

 4/5

 2/5

 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The one-hour combined male/female LC50 (nominal concentrations) was determined to be 1257 ppm with 95%
confidence limits of 1175-1320 ppm in rats.