Registration Dossier

Administrative data

Description of key information

The key acute oral study was conducted according to OECD 423 (Acute Toxic Class method), giving an LD50 for male and female rats in the range > 200 - < 2000 mg/kg when dosed in corn oil (Laboratory of Pharmacology and Toxicology, 2002). Clinical signs observed included reduced motility, ataxia, reduced muscle tone, dyspnoea, lateral position and ptosis at the higher dose level. At the lower dose level no animals showed any signs of systemic toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

The key acute inhalation study was conducted according to OECD 403, giving an LC50 of 1352 ppm  for one-hour, whole-body exposure (Dow Corning Corporation, 1997). Longer exposure times were not used due to the corrosivity of the test substance. Clinical signs and necropsy findings reflected the corrosive nature of the test substance.

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:
2002-05-06 to 2002-07-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
There were minor deviations from the guideline with respect to selection of dose levels.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
Doses of 2000 and 200 mg/kg bw were used, the guideline recommends 2000 followed by 300 mg/kg bw.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: male: 41 days, female: 48 days
- Weight at study initiation: male: 173-241 g; female: 169-173 g
- Fasting period before study: 16 hours before administration of test substance, only tap water ad libitum was available
- Housing: during 14 day observation period groups of 2 -3 animals in MAKROLON cages (type III).
- Diet (e.g. ad libitum): ssniff R/M-H V 1530 (ssniff Spezialiäten GmbH)
- Water: drinking water ad libitum
- Acclimation period: at least 5 adaption days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C+-3°C
- Humidity (%): 55% +-15%
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
only for dose level of 200 mg/kg bw
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/l
- Administration volume: 1.68 ml/kg bw
- Lot/batch no. (if required):81K2204, SIGMA ALDRICH Chemie GmbH

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg b.w. without vehicle
Administration volume: 1.68 ml/kg b.w.

Doses:
2000 mg/kg bw without vehicle
200 mg/kg bw in vehicle (corn oil)
Administration volume: 1.68 ml/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 3 (male) animals
200 mg/kg bw: 3 male, 3 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: before and immediately at 5, 15, 30 and 60 minutes, as well as 3, 6, and 24 h after administration, all surviving animals once a day until all symptoms subsided, thereafter each working day. Observations on mortality once daily, individual body weights were recorded before administration and thereafter in weekly intervals up to the end of the study
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed, the method used was not intended to allow the calculation of a precise LD50 value.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg bw resulted in the death within 60 min of all (male) animals
200 mg/kg bw: none of 3 male and one of 3 female animals died prematurely (within 7 days)
Clinical signs:
2000 mg/kg bw: reduced motility, ataxia, reduced muscle tone, dyspnoea, lateral position, ptosis
200 mg/kg bw: no animals showed any signs of systemic toxicity.
Body weight:
All surviving animals gained the expected body weight within the study period.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Summarized results of acute oral toxicity of the test substance

 

symptomes /

criteria

2000 mg/kg b.w.

200 mg/kg b.w.

male (n=3)

male (n=3)

female (n=3)

Reduced motility

++

5’ - 15’

(3)

-

-

Ataxia

++

5’ - 15’

(3)

-

-

Reduced muscle

tonus

++

5 ’- 15’

(3)

-

-

Dyspnoea

++ - +++

5’ – 30’

(3)

-

-

Lateral position

+

30’

(3)

-

-

Ptosis

+

5’ – 30’

(3)

-

-

Mortality

 

within 6 h

within 2 d

within 7d

within 14 d

 

 

3

3

3

3

 

 

0

0

0

0

 

 

0

0

1

1

Mean weight in g

 

start

after 7 days

after 14 days

 

 

237.3

-

-

 

 

179.0

228.7 (+27.7)

274.7 (+53.6)

 

 

171.0

194.6 (+13.7)

210.5 (+23.1)

Inhibition of

body weight gain

none

none

none

Autopsy findings

none

none

none

+        = slight                        -                    = not observed

++     = moderate             in brackets:      = body weight:     gain in %

+++   = severe                                           = clinical signs: animals affected

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
A reliable study conducted according to OECD 423 and in accordance with GLP, identified an acute oral LD50 value of 200 - 2000 mg/kg bw in male and female rats.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
200 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:
1996-06-27 to 1997-07-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
exposure time: 1 hour
GLP compliance:
yes
Test type:
other: whole body inhalation
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not stated
- Age at study initiation: approx. 5-6 weeks
- Weight at study initiation: approx. 75-100g
- Housing: individually in suspended stainless steel, wire mesh bottom cages,
- Diet (e.g. ad libitum): Purina Certified Rodent Chow
- Water (e.g. ad libitum): via automatic watering system
- Acclimation period: one week prior to initiation of the study

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

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: PVC and plexiglas whole body chamber
- Exposure chamber volume: 175 liter
- Source and rate of air: room air, 45 air changes per hour
- Method of conditioning air: filtered (HEPA and activated carbon)
Test article was introduced into the camber through a special designed stainless steel J-tube containing stainless steel beads and wrapped with heating tape and insulation to facilitate vaporization of test article. The test article was metered from a reservoir into J-tube by a Fluid Metering, Inc. pump. Dry air (Michigan Airgas, Zero Grade) flowed through the J-tube at a controlled rate and air/vapour mixture passed into the inlet port at the top of the chamber where it was mixed with chamber supply air prior to introduction into the chamber.
- test atmosphere monitoring:
1. measuring the chloride ion concentration at the end of the delivery stream from the J-tube with an electrolytic conductivity detector (The chloride equivalents calculated for the nominal concentration of the test article were compared with the level of chloride equivalents at the end of the delivery stream from the J-tube).
2. a Hewlett Packard 5890 gas chromatograph (GC) /5972 mass spectrometer (MS) to monitor the test article concentration in the chamber and provide MS analysis of the chamber atmosphere.
- Temperature, humidity, air flow in chamber: 20.3-21.1 °C, 31.5-33%, 129.7-131.0 LPM,
- Nominal concentration:
the amount of test concentration was determined by pre- and post-exposure weight of the test article in the reservoir. The exposure duration, test article used, and volume of air passing through the chamber were used to calculate nominal concentration values.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC/MS
Duration of exposure:
1 h
Concentrations:
nominal concentration: 1123; 1317; 1414 ppm
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:
clinical signs: once per day for 14 days following exposure (including respiratory, behavioural, nasal and/or ocular changes.
mortality/morbidity: twice daily on weekday, once on weekends/holidays
body weight: prior to exposure, on day 1, 8, and 15
gross pathology: all animals that died during the study or at the end of 14 day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
LC50, 95% fiducial limits, and approx. slope of dose response curve were calculated using a SAS/STAT probit program. Body weight means and SD were also calculated.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 352 ppm
Based on:
test mat.
95% CL:
> 1 254 - < 1 455
Exp. duration:
1 h
Mortality:
at 1123 ppm: all animals survived until the end of the 14-day observation period.
at 1317 ppm: 4 animals (2 males, 2 females) died by study day 5.
at 1414 ppm: 7 animals ( 3 males, 4 females) died by study day 4.
Clinical signs:
other: Respiratory, activity, ocular and nasal effects and facial and body soiling were noted in all groups during 14-day observation period. Respiratory effects noted included laboured breathing and rales. The activity effects which were most frequently noted i
Body weight:
Mean body weights for all the groups were depressed at the end of the first week. All surviving animals except for the one female in group 3, gained weight by the end of the 14-day observation period.
Gross pathology:
Test article-related effects observed included corneal opacities, exphthalmos, buphthalmose, and alopecia, lung, nasal, and eye effects. Discoloration of hair were observed in a majority of the animals that died during 14-day observation period. Lung effects noted in these animals included haemorrhage, congestion, and/or consolidation and ectasia.The primary nasal effect was obstructed nostrils. The primary eye effect observed was crusted shut eyelids. Discoloration of the hair was mostly due to porphyrin and greenish staining. Discoloration of the extremities and congestion of the meningeal vessels was noted in a majority of the animals to 1414 ppm that died during the study. Blood in the gastrointestinal tract was noted in few of the animals exposed to 1414 ppm that died during the study. Gaseous distension and a decrease or absence of body fat was noted in a majority of the animals exposed to 1317 that did not survive the observation period.
Other findings:
The nominal exposure concentrations were significantly higher than the measured chamber test article concentrations (394, 440, 510 ppm, respectively) due to the reactivity and hydrolysis of the test article.

                                                    Summary of Mortality data

 

Exposure Group

Nominal Exposure

Concentration (ppm)

Number Dead /Number Exposed

 

     Males                Females 

 Males / Females

       Combined

1

1123

       0/5                      0/5

         0/10

2

1317

       2/5                      2/5

         4/10

3

1414

       3/5                      4/5

         7/10

 

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
A reliable study conducted according to OECD and in accordance with GLP, identified a 1h acute inhalation LC50 value of 1352 ppm in male and female rats.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key oral and key inhalation studies were selected as the only available studies. Both were GLP-compliant, guideline studies (reliability 1).

The inhalation LC50 is from a one hour exposure period. When this value is adjusted (divided by 2) to account for the short exposure duration, the LC50 (equivalent to 4-h exposure) becomes 676 ppm, or approximately 5 mg/l (5000 mg/m3).


Justification for classification or non-classification

On the basis of the available measured LD(C)50 values, trichloro(propyl)silane is classified 'Acute toxic 4 (oral)' and 'Acute toxic 3 (vapour)' according to Regulation (EC) No 1272/2008.