Methylsilanetriyl triacetate

Acute Toxicity: oral

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

Test material information

Constituent 1

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 levels

Effect levels 1

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

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 550 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 437 - <= 1 661

Effect levels 3

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:

other: 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 uri

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
800^a	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.