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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12.01.2000 to 06.02.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Methylsilanetriyl triacetate
EC Number:
224-221-9
EC Name:
Methylsilanetriyl triacetate
Cas Number:
4253-34-3
Molecular formula:
C7H12O6Si
IUPAC Name:
methylsilanetriyl triacetate
Details on test material:
- Name of test material (as cited in study report): Methyltriacetoxysilane
- Substance type: Si- carboxylate
- Physical state: Crystalline solid
- Stability under test conditions: No data
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, New York
- Age at study initiation: 9-12 weeks
- Weight at study initiation: Males: 254-321 g; Females: 193-238 g
- Fasting period before study: yes
- Housing: Individually housed in suspended stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: at least 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26
- Humidity (%): 26-72
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17.02.2000 To: 12.05.2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
melted state
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.6 ml/kg
Doses:
800, 1300, 1450, 1600, 1750 and 2000 mg/kg bw/day
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: Viability observations were made twice daily. Observations for clinical signs of toxicity were made 1, 2 and 4 hours after dosing and daily thereafter. Animals were weighed on the day before dosing, just prior to dosing, then on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: each animal's feed was visually inspected and compared to that of the other animals in the same test. Macroscopic examination of all animals.
Statistics:
An estimate of the median lethal dose, with 95% confidence limits, using the method of Litchfield and Wilcoxon was performed for the combined sexes, and individually for males and females.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 516 - <= 1 694
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 550 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 437 - <= 1 661
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 660 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 545 - <= 1 780
Mortality:
See Table 1
Clinical signs:
Observations noted in most groups on the day of dosing included red stains on the snout/extremeties, lacrimation, excessive salivation, decreased activity, lethargy and/or prostate, irregular gait, hunched appearance, laboured breathing, rales and red urine, red stains of the ano-genital area and/or red stains beneath animal's cage. The clinical sign of irregular gait appeared to be generally associated with mortality. Additional observations observed in most groups on the day after dosing included yellow ano-genital stains, decreased food consumption and decreased fecal volume or no stool. Most survivors were free of signs of toxicity by test day 11.
Body weight:
Most 800 and 1300 mg/kg males and females gained weight at both 7 and 14 days after dosing (Days 8 and 15); a few males lost weight by Day 8; and/or Day 15. Most 1450 and 1600 mg/kg males lost weight by Day 8, but gained weight by Day 15. Most surviving females at 1600 and 1750 mg/kg gained weight by Days 8 and 15.
Gross pathology:
All of the rats in 800 and 1300 mg/kg group had necropsy findings within normal limits. The stomach of the rats at 1450, 1600, 1750 and/or 2000 mg/kg had abnormal contents (clear, mucinous, granular, tan, black, green), discoloured mucosa (red, brown, black) and an increased thickness of the wall. A number of these rats also had adhesions between the stomach and other abdominal viscera. Two rats at 2000 mg/kg had fluid in the abdominal cavity.
Other findings:
None

Any other information on results incl. tables

Table 1 Summary of Mortality data

 Dose Level (mg/kg)   Mortality       Time of death
   Males  Females  Combined  
 800a  0/5  0/5  0/10  
 1300  0/5  0/5  0/10  
 1450  1/5  -  -  Day 14
 1600  4/5  1/5  5/10  2 hours, Day 3, 4, 5, 9
 1750  -  4/5  -  Day 3, 4, 7
 2000  5/5  5/5  10/10  4, 22 hours, Day 2, 3, 6, 8

a Results from this dose group not used in LD50 determination

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (reliability score 1) the LD50 for methylsilanetriyl triacetate was 1600 mg/kg bw in rats. Observations noted in most groups on the day of dosing included red stains on the snout/extremeties, lacrimation, excessive salivation, decreased activity, lethargy and/or prostate, irregular gait, hunched appearance, laboured breathing, rales and red urine, red stains of the ano-genital area and/or red stains beneath animal's cage. The clinical sign of irregular gait appeared to be generally associated with mortality. Most 1450 and 1600 mg/kg males lost weight by Day 8, but gained weight by Day 15. Most surviving females at 1600 and 1750 mg/kg gained weight by Days 8 and 15. The stomach of the rats at 1450, 1600, 1750 and/or 2000 mg/kg had abnormal contents (clear, mucinous, granular, tan, black, green), discoloured mucosa (red, brown, black) and an increased thickness of the wall. A number of these rats also had adhesions between the stomach and other abdominal viscera. Two rats at 2000 mg/kg had fluid in the abdominal cavity.