N,N',N''-tributyl-1-methylsilanetriamine

Endpoint summary

Description of key information

Based on the available information from the key acute oral toxicity study, the LD50 for N,N',N''-tributyl-1-methyl-silanetriamine was concluded to be between 300 and 2000 mg/kg bw. The study was conducted according to OECD test guideline 423 and to GLP (BSL Bioservice, 2004).  

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:

10/05/2004 - 27/05/2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: HsdBrlHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH
- Age at study initiation: not included
- Weight at study initiation: 152-172 g
- Fasting period before study: overnight
- Housing: Macrolon cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice ad libitum
- Water (e.g. ad libitum): tap water
- Acclimation period: adequate acclimation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

starting dose of 2000 mg/kg bw
second and third doses of 300 mg/kg bw

No. of animals per sex per dose:

3 females - 2000 mg/kg bw
step 1: 3 females - 300 mg/kg bw
step 2: 3 females - 300 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed prior to the treatment and once a week thereafter. Three observations were made within the first four hours after the administration of the article, then daily for the 14-day study period.
- Necropsy of survivors performed: yes
- Other examinations performed: Particular attention was paid to changes in the skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Also, attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The criteria for determining exact LD50, in accordance with OECD TG 423 were not met; however, based on the 100% mortality at the 2000 mg/kg dose (high dose), it is concluded that the result falls into CLP criteria IV (<2000 mg/kg bw)

Mortality:

The dosage of 2000 mg/kg bw caused 100 % mortality within 100 minutes post-dose.
The dosage of 300 mg/kg bw did not cause any mortality in the 2 groups of females tested within 14 days post-dose.

Clinical signs:

The rats treated with 2000 mg/kg bw experienced reduced spontaneous activity, apathy, prone position, convulsions, incoordination, disturbed locomotor system, laboured respiration, cyanotic head, extremities and tails within 100 minutes after the treatment. No clinical signs of toxicity were observed in the first group of animals treated with 300 mg/kg bw. The second group of animals treated with 300 mg/kg showed signs of apathy and rough coat for the first 30 minutes post-dosage. 60 minutes after the treatment no clinical changes were observed.

Body weight:

Throughout the 14-day study observation no weight loss was recorded in the two groups of rats treated with 300 mg/kg bw. The weight gain that was experienced by them was within the expected range.

Gross pathology:

The animals treated with 2000 mg/kg bw had cyanotic cutaneous mucosa, bloody gastric and small intestine mucosa, and bloody contents were found at necropsy. No gross pathological changes were found in the two groups of animals treated with 300 mg/kg bw.

Other findings:

Acute injection of blood vessels in the abdominal region was observed, which was due to the euthanasia injection.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

An LD50 for N,N',N''-tributyl-1-methyl-silanetriamine was concluded to be between 300 and 2000 mg/kg bw. The study was conducted according to OECD test guideline 423 and to GLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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

The key study for acute oral toxicity, conducted according to OECD TG 423 and in compliance with GLP, reports an LD50 of >300 to < 2000 mg/kg bw in female rats for N,N',N''-tributyl-1-methylsilanetriamine (BSL Bioservice, 2004).

At 2000 mg/kg bw, the clinical signs observed included reduced spontaneous activity, apathy, prostration, convulsions, incoordination, disturbed locomotor system activity, laboured respiration, cyanotic head, extremities and tails. All 3 animals in the 2000 mg/kg bw group were deceased by 100 minutes post-treatment. At necropsy, cyanotic cutaneous mucosa, bloody gastric and small intestine mucosa, and bloody contents were observed.

At 300 mg/kg bw, the 6 female rats tested, showed no evident body weight or pathological changes within the 14-day observation period. There were no mortalities. Rough coat and signs of apathy were observed from 30 minutes until 60 minutes post-treatment. No gross pathological changes were found in the animals treated with 300 mg/kg bw.

Justification for classification or non-classification

Based on the available data, N,N',N''-tributyl-1-methylsilanetriamine is classified for Acute Oral Toxicity, Category 4, 'H302: Harmful if swallowed' according to Regulation (EC) No 1272/2008.