Registration Dossier

Administrative data

Description of key information

In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (Huntingdon Life Sciences, 2001) the LD50 for methylsilanetriyl triacetate was 1600 mg/kg bw in rats.

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as the substance is classified as corrosive.

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the dermal route (required in Section 8.5.3) does not need to be conducted as the substance is classified as corrosive.

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:
12.01.2000 to 06.02.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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
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.
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

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

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.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 600 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an acute oral toxicity study conducted to the now deleted OECD 401 and to GLP (Huntingdon Life Sciences, 2001) 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 anogenital 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. In a gastric juice simulation study (Ying et al., 2002; see Section 4.1.1.1) in which methylsilanetriyl triacetate was added to simulated gastric juice, relatively high molecular weight polymers were found after 1 and 4 hours. This finding indicates that at very high gavage doses polymerisation could occur in the stomach. Therefore the abnormal stomach contents observed in the above study could have been polymerised test substance.  Clinical signs and macroscopic findings appeared to be related to the corrosive properties of the test substance on the stomach.  

Since one mole of silane (220g) produces three moles (180g) of acetic acid, it is expected that the LD50 for the silane would be (220/180)*LD50 of acetic acid. So, if the LD50 for the acid is 1083 mg/kg bw (as reported in SIAR, 2006), then the LD50 of the silane would be ca.1324 mg/kg bw. This assumes that the silanol does not contribute to the intrinsic toxicity of the substance.

The calculated value is in good agreement with the reported LD50 of methylsilanetriyl triacetate of 1600 mg/kg bw (rat), confirming the above assumption.




Justification for classification or non-classification

Based on the available data methylsilanetriyl triacetate is classified for acute oral toxicity Category 4, 'H302: Harmful if swallowed' according to Regulation (EC) No 1272/2008.