Registration Dossier

Administrative data

Description of key information

In the key oral and inhalation acute studies clinical signs were recorded that were considered to be attributable to the corrosive properties of hydrogen chloride, formed by the rapid hydrolysis of the parent substance, dichloro(dimethyl)silane. The acute inhaled LC50 value from the key study was derived from a 1 hour exposure period, so this value was adjusted (divided by 2) to account for the shorter exposure period. Other oral and inhalation acute studies showed effects consistent with the key studies.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08.08.1989 to 22.08.1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: 7-10 weeks
- Weight at study initiation: Average maximum weights: Males 174 g; females 167 g
- Fasting period before study:
- Housing: Type III Macrolon cages (5 per cage)
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Four days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 50±10
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: Not clear - needs translation
Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
VEHICLE - might be more information, but cannot translate
- Concentration in vehicle: No data
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw


DOSAGE PREPARATION (if unusual): Not clear from German report
Doses:
125, 500, 707 and 1000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed twice daily, body weights measured before dosing, and on day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed:gross examinations performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
595 mg/kg bw
Mortality:
All animals in the 1000 mg/kg bw group died approximately one hour after application. After 707 mg/kg bw animals died between three hours and five days. No animals died in the 125 and 500 mg/kg bw group.
Clinical signs:
Clinical signs for the 500 and 707 mg/kg bw were ruffled coat and general poor condition. At 1000 mg/kg bw rats showed ruffled fur, laboured breathing and sedation. The symptoms were mild to moderate, occurred approximately 30 minutes after dosing, and lasted for up to three days or until death. After 125 mg/kg bw ruffled fur was the only clinical sign observed. All surviving animals were asymptomatic by day 4.
Body weight:
Needs translation
Gross pathology:
Gastrointestinal tract dark red or black, red pancreas, brown mottled liver in the 707 and 1000 mg/kg bw.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study (reliability score 1) conducted to the now deleted OECD 401 and GLP, the LD50 for dichloro(dimethyl)silane was 595 mg/kg bw in rats.
Executive summary:

In an acute oral toxicity study (reliability score 1) conducted to the now deleted OECD 401 and GLP, dichloro(dimethyl)silane (in paraffin oil) was administered by oral gavage to Wistar rats (five/sex/dose) at doses of 125, 500, 707 and 1000 mg/kg bw. Animals were then observed for 14 days, twice daily. Body weights were measured before dosing, and on days 7 and 14. All animals were examined macroscopically. All animals in the 1000 mg/kg bw group died approximately one hour after application. After 707 mg/kg bw animals died between three hours and five days. No animals died in the 125 and 500 mg/kg bw group. Clinical signs for the 500 and 707 mg/kg bw were ruffled coat and general poor condition. At 1000 mg/kg bw rats showed ruffled fur, laboured breathing and sedation. The symptoms were mild to moderate, occurred approximately 30 minutes after dosing, and lasted for up to three days or until death. After 125 mg/kg bw ruffled fur was the only clinical sign observed. All surviving animals were asymptomatic by day 4. Necropsy revealed dark red or black gastrointestinal tract, red pancreas, brown mottled liver in the 707 and 1000 mg/kg bw. The LD50 was calculated to be 595 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
595 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15.11.1996 to 22.12.1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The restriction was that the exposure duration was only one hour.
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
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
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: The animals were loaded into the exposure caging using a staggered by sex arrangement. This exposure caging was circular and divided into approximately 10 equally sized pie-shaped sections. Cage diameter was 21 inches and 6 inches high.
- 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 (nominal); 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.
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 groups 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 grey 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), discoloured, 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

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






.

Interpretation of results:
Category 3 based on GHS criteria
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 grey areas on lungs, no significant test substance-related effects were noted in animals exposed to 1309 ppm.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
5 521 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Dichloro(dimethyl)silane is rapidly hydrolysed to dimethylsilanediol and hydrogen chloride in the presence of moisture, so the adverse effects observed following acute exposure by all routes were considered to be due to local corrosive effects of the hydrogen chloride.

In the key oral acute study (Bayer AG, 1990) the main clinical signs were mild to moderate ruffled coat, general poor condition, laboured breathing and sedation and occurred approximately 30 minutes after dosing, and lasted for up to three days or until death. The oral LD50 was defined as 595 mg/kg. In the key inhalation study (Dow Corning Corporation, 1997) clinical signs were staining/soiling around the nose, mouth and/or eyes and other body surfaces, lacrimation, salivation, respiratory effects (laboured breathing, rales), partial or complete eye closure, and unilateral or bilateral ocular/corneal opacities. The LC50 value of 2092 ppm from the study was derived from a whole body one-hour vapour inhalation, therefore this value was adjusted (divided by 2) to account for the short exposure period and so becomes 1046 ppm which is equivalent to 5521 mg/m3.

Other oral and inhalation acute studies showed effects consistent with the key studies.


Justification for classification or non-classification

Based on the available data dichloro(dimethyl)silane is classified as acute toxic Cat. 4 (oral) and acute toxic Cat. 3 (vapour) according to Regulation (EC) No 1272/2008.