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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:
01.12.95 to 31.12.95
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an 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:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
one hour exposure period due to corrosivity of test substance
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Trichloro(vinyl)silane
EC Number:
200-917-8
EC Name:
Trichloro(vinyl)silane
Cas Number:
75-94-5
Molecular formula:
C2H3Cl3Si
IUPAC Name:
trichloro(vinyl)silane

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: Approximately 6 weeks old when received
- Weight at study initiation: 75-100 g when received
- Fasting period before study: No data
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Ad libitum, except during exposure
- Water (e.g. ad libitum): Ad libitum, except during exposure
- Acclimation period: One week


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-78
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 5.12.95 To: 27.12.95

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: not applicable
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: Wire mesh caging
- Source and rate of air: Filtered room air at 44-45 air changes per hour.
- Method of conditioning air: HEPA and activated carbon
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Slight negative pressure, temperature was monitored but no information in study report, humidity was controlled to influence the hydrolysis of the test substance.


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatograph and mass spectrometer.
- Samples taken from breathing zone: no information, but probably not as animals free to move in chamber.


Analytical verification of test atmosphere concentrations:
yes
Remarks:
four samples during each exposure
Duration of exposure:
1 h
Remarks on duration:
Exposure period was shorter than guideline recommendation of 4 hours due to corrosive nature of test substance.
Concentrations:
500, 575 665 and 832 (Mean chamber concentration). Nominal chamber concentrations (1186, 1681, 1605 and 1989, respectively) were significantly higher than the actual concentrations due to hydrolysis of the test substance.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were once per day for 14 days (twice per day for mortality). Body weights measured on Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination of all animals.
Statistics:
The inhalation median lethal concentration (LC50), 95% fiducial limits, and approximate slope of the dose response curve were calculated using a SAS/STAT Probit method.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 1 611 ppm
95% CL:
>= 1 505 - <= 1 724
Exp. duration:
1 h
Remarks on result:
other: PREFERRED VALUE - based on nominal chamber concentrations
Sex:
male/female
Dose descriptor:
LC50
Effect level:
631 ppm
95% CL:
589 - 689
Exp. duration:
1 h
Remarks on result:
other: based on mean chamber concentrations.
Mortality:
All animals at the highest dose died. Six and three animals died at 665 ppm and 575 ppm, respectively. No animals died at the lowest dose.
Clinical signs:
other: Respiratory, eye and nasal effects and soiling were observed in all groups. Activity effects were also noted in animals exposed to 575, 665 and 832 ppm of the test material. Respiratory effects in all groups included labored breathing, rales and gasping. 
Body weight:
A majority of the surviving animals gained weight by the end of the 14-day observation period. However, weight loss was noted in surviving animals exposed to 575 and 665 ppm at the end of the first week. 
Gross pathology:
No significant test article-related gross pathological findings were noted in animals at the terminal sacrifice. Test article-related gross pathological findings noted in a majority of animals which died during the 14-day observation period included hemorrhage, congestion and/or consolidation of the lungs, discoloration and/or staining of hair, and/or staining of hair due to porphyrin pigment. Blood in the gastrointestinal tract and discoloration of extremities was noted in a majority of animals which died that were exposed to 832 ppm and a few of the animals which died that were exposed to 575 and 665 ppm of the test material.

Any other information on results incl. tables

Number of deaths at each dose level:

Sex

Dose level - actual chamber concentrations (ppm)

No. Deaths

Males

500

0/5

575

2/5

665

4/5

832

5/5

Females

500

0/5

575

2/5

665

4/5

832

5/5

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a good quality acute inhalation study conducted according to OECD 403 and GLP (reliability score 1), with the exception that the exposure period was 1-hour due to the corrosive nature of the test substance, the LC50 for trichloro(vinyl)silane was 1611 ppm in rats.
Executive summary:

In a good quality acute inhalation study conducted according to OECD test guideline 403 and GLP, Sprague-Dawley rats were exposed to trichloro(vinyl)silane at mean chamber concentrations of 500, 575, 665 and 832 ppm (nominal chamber concentrations 1186, 1681, 1605 and 1989, respectively), for one hour (reduced exposure duration due to corrosive nature of test substance). All animals exposed to the highest concentration died. Six and three animals died at 665 ppm and 575 ppm, respectively. No animals died at the lowest concentration. Respiratory (labored breathing, rales and gasping), eye (corneal opacities, alopecia around eyes, drainage/discharge from eyes, dried material eyes and closed or partially closed eyes) and nasal (dried material/crustation on and around the nose) effects and soiling were observed in all groups. Hypoactivity, ataxia and lethargy were also noted in animals exposed to 575, 665 and 832 ppm of the test material. There were no significant test article-related clinical signs noted at the end of the 14 day observation period. The majority of the surviving animals gained weight by the end of the 14-day observation period. However, weight loss was noted in surviving animals exposed to 575 and 665 ppm at the end of the first week. No significant test article-related gross pathological findings were noted in animals at the terminal sacrifice. Test article-related related gross pathological findings noted in a majority of animals which died during the 14-day observation period included hemorrhage, congestion and/or consolidation of the lungs, discoloration and/or staining of hair, and/or staining of hair due to porphyrin pigment. Blood in the gastrointestinal tract and discoloration of extremities was noted in a majority of animals which died that were exposed to 832 ppm and a few of the animals which died that were exposed to 575 and 665 ppm of the test material.

In the original study the one-hour LC50 value was calculated to be 631 ppm based on actual chamber concentrations. However, the LC50 based on mean chamber concentrations ignores the contribution from hydrolysis products. Therefore, in an amendment to this study Spearman-Karber analysis was conducted using nominal chamber concentrations and mortality data to produce an LC50 value of 1611 ppm, with 95% confidence interval of 1505 -1724 ppm. This is the preferred LC50 for this study.