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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
15.11.1996 to 22.12.1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2b The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restriction was that the exposure duration was only one hour.

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:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
one hour exposure duration
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dimethyldichlorosilane
- Substance type: Chloroilane
- Physical state: Colourless liquid
- Stability under test conditions: Stable only in an inert atmosphere, hydrolyses in presence of moisture
- Storage condition of test material: Room temperature in a closed container in a ventilated storage cabinet

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Raleigh, NY
- Age at study initiation: Approximately 8 weeks old
- Weight at study initiation: 170 +/- 21 g (males) and 122 +/- 10 g (females)
- Fasting period before study: No data
- Housing: Individually in suspended stainless steel, wire mesh bottomed 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): 64-79
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 19.11.1996 To: 11.12.1996

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: Plexiglass whole body chamber operated under dynamic conditions
- Exposure chamber volume: 175 litre
- Method of holding animals in test chamber: Just exposure chamber
- Source and rate of air: Room air at approximately 45 air changes per hour to ensure a T99 of approximately six minutes.
- Method of conditioning air: Room air was filtered using HEPA and activated carbon
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: 22 ±2oC, 30-35%, and slight negative pressure.


TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatograph mass spectrometer equipped with an automated Valco injector valve and thermal conductivity detector.
- Samples taken from breathing zone: No data
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GM-MS
Duration of exposure:
1 h
Concentrations:
1309, 2077, 2353 and 2726 ppm (measured); 1500, 2000, 2700 and 2400 ppm (target)
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: Observations were made immediately following exposure and once per day for 14 days. Body weights were measured prior to exposure, and on days 1, 8, and 15.
- Necropsy of survivors performed: yes, all animals had a gross pathological examination.
- Other examinations performed: none reported
Statistics:
The inhalation median lethal concentration, 95% fiducial limits and approximate slope of the dose response curve were calculated using a SAS/STAT Probit procedure. Body weight means and standard deviations were also calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2 092 ppm
95% CL:
> 1 492 - <= 2 240
Exp. duration:
1 h
Mortality:
See table 1 below
Clinical signs:
other: Description, severity, time of onset and duration of clinical signs at each dose level: All rats on the study exhibited various staining/soiling around the nose, mouth and/or eyes and other body surfaces, lacrimation and salivation.  These latter two sig
Body weight:
No weight loss was observed in the 1309 ppm group. However, the majority of surviving animals in the 2077 and 2353 ppm goups had significant weight loss by study day 8. By the end of the observation period, these animals had regained the majority or all of their weight loss.
Gross pathology:
A total of 17 rats survived to the scheduled necropsy.  Various ocular abnormalities (opacity, hemorrhage, dark red areas, rupture, etc.) were seen for 14 of these rats.  Twelve exhibited pulmonary abnormalities, primarily consisting of areas of gray discoloration and red foci.  Ten survivors exhibited various external stains, hair losses and misshapen, shrunken or missing extremities. A total of 23 rats died on the study, but none in the 1309 ppm group.  Necropsy findings seen in more than one-half of the rats that died and in all groups where deaths occurred included various external stains, mattings and hair losses (N = 23), discolored, encrusted, firm and/or obstructed nares/nostrils (N = 22), pulmonary abnormalities consisting of ectasia, congestion, hemorrhage and discoloration (N = 22), gastrointestinal findings consisting of abnormal contents, gaseous distension and empty (N = 22), decreased or absent body fat (N = 19), various ocular abnormalities including corneal opacities, pannus and abnormal anterior chamber contents (n = 15), liver findings of red/congested, small and dark or pale and soft (N = 15) and small and/or dark spleens (N = 12).  In addition, encrustation on the forefeet was seen in 11 rats, but not in the 2353 ppm group.  There were no other remarkable necropsy findings in rats that died. Potential target organs were identified as being the lungs/respiratory tract and eyes.
Other findings:
Responses were generally consistent between males and females except with respect to mortality, where the males appeared to be more sensitive than the females

Any other information on results incl. tables

Table 1 Number of deaths at each dose level:
        Dose level (ppm)  No. Deaths        Days to Death
Males        
        1309                      0               N/A
        2077                      4               6, 6, 6, 7
        2353                      5               4, 5, 6, 7, 9
        2726                      5               3, 4, 4, 5, 7
Females        
        1309                      0               N/A
        2077                      1               7
        2353                      3               6, 6, 7
        2726                      5               5, 5, 5, 5, 6






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Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a good quality acute inhalation toxicity study (reliability score 2) conducted to OECD 403 (except for an exposure duration of one hour), and GLP, the one-hour combined male/female LC50, based on nominal concentrations, was determined to be 2092 ppm with 95% confidence limits of 1492-2240 ppm in rats.
Executive summary:

In a good quality acute inhalation toxicity study (reliability score 2) conducted to OECD 403 (except for an exposure duration of one hour), and GLP, Fischer 344 rats (5/sex/group) were exposed for one hour to 1309, 2077, 2353 and 2726 ppm (nominal concentrations) of dimethyldichlorosilane vapour, and then observed for 14 days. Gross necropsies were performed on all animals, and body weights throughout the study recorded. All animals exposed to 1309 ppm survived until the end of the l4-day observation period. Five animals (four males and one female) died in the group exposed to 2077 ppm. All of the animals exposed to 2726 ppm and eight animals (five males and three females) exposed to 2353 ppm died by the end of the l4 -day observation period. The LC50 was calculated to be 2092 ppm. During the l4 -day observation period, lacrimation, salivation, oil around nose and mouth, and urine staining was noted in all groups. Respiratory effects, effects on activity and green staining of fur were frequently noted in animals exposed to 2077, 2353, and 2726 ppm. Ocular effects such as corneal opacities were noted in animals exposed to 1309, 2077 and 2353 ppm. Test article-related gross pathological findings were noted in lungs, gastrointestinal tract, nasal region, and external body of animals exposed to 2017, 2353 and 2726. With the exception of ocular effects and gray areas on lungs, no significant test substance-related effects were noted in animals exposed to 1309 ppm.