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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:
1998/11/19-2000/10/03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD guideline and in compliance with GLP.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Principles of method if other than guideline:
A modification involving an increased chamber airflow rate (44-46 changes per hour), an expanded chamber temperature range (22± 3°C vs. 22 ± 2°C) and a shortened (1 hour vs. 4 hours) exposure period.
GLP compliance:
yes
Test type:
other: 1 hour LC50
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

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

- Source: Charles River Laboratories, Raleigh, North Carolina, RO2 Facility

- Age at study initiation: ca. 7 weeks

- Weight at study initiation: 117.8-144.5g females, 142.8-182.9g males

- Fasting period before study:

- Housing: During the in-life phase of the study, the animals were housed in animal room #218 within Dow Corning Corporation's Health and Environmental Sciences Laboratory. Animals were individually housed in clean suspended wire-mesh cages (ca.7"x10"x7") during both the quarantine and the in-life phase of the study. The animals were transferred to clean cages at least once every two weeks.

- Diet: Certified Rodent Chow #5002, ad libitum except during exposure period.

- Water: Reverse osmosis purified waster was provided ad libitum, except during the exposure period via automatic watering system.

- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 64-79

- Humidity (%): 30-70

- Air changes (per hr): 10-15

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


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: The test substance was introduced into a heated (100-120°C) stainless steel J-tube containing column of stainless steel ball bearings at a controlled rate utilizing a FMI pump. Nitrogen, passing through the J-tube at a rate of 8 litres per minute, served as the garrier gas for vapour generation and transfer of dimethylhydrogenchlorosilane vapour from the vapour generator to the exposure chamber.

- Exposure chamber volume: 175 litres

- Method of holding animals in test chamber: A wire mesh cage specifically designed for use in the exposure chamber. The exposure caging was circular in shape and divided into 10 equal sized triangular -shaped compartments. The animals were placed into the exposure compartments, one rat per compartment, arranged in a 'staggered by sex' configuration around the exposure caging.

- Source and rate of air:The dimethylhydrogenchlorosilane vapour/nitrogen gas carrier stream (compressed air) in the chamber in-let tube to form the test atmosphere. The total airflow into the chamber was ca. 130 lpm as calculated from the differential pressure across an orifice plate located in the lower portion of the chamber inlet.

- Temperature, humidity, pressure in air chamber: The chamber was operated at a slight negative pressure relative to the room. Chamber atmosphere flow rate, temperature and relative humidity were monitored continuously and recorded at intervals of ca. 10 min. A control chamber was set up just for the purpose of estimating chamber temperature and relative humidity.


TEST ATMOSPHERE

- Brief description of analytical method used: Analysis of the chamber atmosphere and dimethylhydrogenchlorosilane vapour/nitrgoen gas carrier stream from the vapour generation system was performed with a gas chromatograph utilising both a thermoconductivity detector and a mass detector.

- Samples taken from breathing zone: yes , the chamber atmosphere was sampled for analysis once just prior to conclusion of the exposure period.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
1 h
Concentrations:
4108, 4179, 4409 and 4589 ppm (nominal)
No. of animals per sex per dose:
Four groups of ten rats (5F, 5M)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Directly after the exposure the animals were transported to the animal room and placed back into their housing caging. During this process each animal was evaluated and clinical observations recorded. Animals were then monitored for an additional 14 days. Clinical observations were recorded daily. Body weights were recorded on the day of randomization and on days 1, 8 and 15.

- Necropsy of survivors performed: yes, animals that survived to the end of the observation period were euthanized and gross necropsy performed. Animals that died prior to the scheduled necropsy were placed into a cold room and a necropsy performed as soon as was practical.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
The mortality data and associated nominal chamber vapour concentrations were used to calculate the LC50 value using probit analysis.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4 478 ppm
Exp. duration:
1 h
Mortality:
Unscheduled deaths were observed at all exposure levels. All unscheduled deaths occurred within 13 days after exposure.
Clinical signs:
other: Respiratory effects (rales, gasping) and ocular effects (lacrimation, corneal opacity) were apparent upon the removal of the animals from the exposure chamber.
Body weight:
Body weight loss was apparent in all exposure groups. Recovery of body mass was common to those animals capable of surviving to study day 15.
Gross pathology:
The primary gross necropsy findings for animals in the unscheduled death category were indicative of animals that had experienced significant lung injury and food/water depravation. Many of the animals surviving to the scheduled necropsy showed no gross pathological signs of injury.
Other findings:
- Potential target organs: The lungs were identified as a potential target organ in the report.   Also, although not specifically identified in the report, clinical signs  and necropsy findings were consistent with the eyes being target organs.

- Other observations: Responses were generally consistent between males and females.

Any other information on results incl. tables

Table 1: Concentrations, exposure conditions and mortality per animals treated

Nominal

Conc. (ppm)

Mortality (# dead/total)

Males

Females

Combined

 4108

 1/5

1/5 

2/10

4179

1/5

1/5

2/10

 4409

 3/5

3/5

6/10

 4589

3/5 

2/5 

5/10 

 

The principle clinical signs were indicative of respiratory/pulmonary and  ocular effects.  Labored breathing, rales and gasping were seen in  

essentially all rats,with the onset of these signs occurring almost  exclusively on the day of exposure.  Some signs of respiratory distress  

persisted well into the post-exposure observation period.  Essentially  all rats were hypoactive and had salivation on the day of exposure; these  

signs generally resolved shortly thereafter.  Nearly all rats had corneal  opacity, generally first observed on the day of exposure.  Ocular  opacities 

persisted to the end of the observation period in more than  one-half of the survivors (as confirmed at necropsy).  Approximately  one-half of the rats 

had lacrimation of short duration early in the  observation period.  Nasal cartilage that was scabbed or absent was seen  in approximately one-half 

of the surviving rats late in the observation  period.  Many signs indicative of stress and/or general unthriftiness  (staining, soiling, encrustation) 

were observed frequently throughout the  study and in all groups.  Signs tended to resolve in survivors as the  observation period progressed, 

however, few survivors appeared fully  normal clinically at the end of the post-exposure observation period.

A total of 25 rats survived to the scheduled necropsy.  Necropsy findings  in more than one-half of the survivors and in all groups were missing,  

misshapen or shrunken extremities (N = 18), various external staining and  hair loss (N = 15), unilateral or bilateral ocular opacities or other  

ocular abnormalities (N = 14), missing or absent nasal pad tissue (N =  13) and consolidation and/or gray discoloration of the lungs (N = 13).   

In addition, seven survivors were observed to have encrustation of the  forefeet.  Fifteen rats died on the study.  Necropsy findings in more  than 

one-half of these rats and in all groups were various external  staining and hair loss (N = 15), pulmonary congestion, consolidation,  hemorrhage, 

ectasia and/or discoloration (N = 13), unilateral or  bilateral ocular opacities or other ocular abnormalities (N = 12), body  fat decreased or absent 

(N= 12), encrustation of the feet (N = 11),  gaseous distension of the gastrointestinal tract (N = 11), obstructed  nostrils (N = 9) dehydration (N = 9) 

and abnormal gastrointestinal tract  contents (N = 8).  In addition, a dried and firm nose, missing, misshapen  or shrunken extremities, nasal 

staining or encrustation and eyelids that  were crusted shut were noted for 6, 6, 5 and 4 rats that died  respectively.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The one-hour combined male/female LC50 value of 4478 ppm (8.66 mg/L) with 95% confidence limits of 4281-63,276 ppm in rats (based on nominal concentrations) was determined in a reliable study conducted according to an appropriate test protocol and in compliance with GLP.