1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine

Endpoint summary

Description of key information

In the key acute oral toxicity study the LD50 for 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine was reported to be 1280 mg/kg bw in rats. The study was conducted to the now deleted OECD 401 guideline and to GLP, (Hazleton, 1989). In an acute dermal toxicity study conducted to OECD TG 402 and in compliance with GLP, the LD50, for 1-Methyl-N,N',N''-tris(1-methylpropyl)silanetriamine, was >2008 mg/kg bw  (Hazleton, 1989).

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:

10/05/1989 - 13/11/1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(now deleted)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Ico rat-IFA.SD. (IOPS. Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Credo, France
- Age at study initiation: 5-7 weeks old
- Weight at study initiation: 120-161 g
- Fasting period before study: 17-18 hours of water only regime
- Housing: housed by sex in groups of 5 in type MI polycarbonate cages
- Diet (e.g. ad libitum): complete pelleted rat-mouse maintenance diet, ad libitum
- Water (e.g. ad libitum): softened and filtered mains water ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-70 % R.H.
- 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: 1781 mg/kg

Doses:

1126 mg/kg, 1411 mg/kg, 1781 mg/kg, 1260 mg/kg, 1596 mg/kg

No. of animals per sex per dose:

5 males and 5 females - 1126 mg/kg
5 males and 5 females - 1411 mg/kg
5 males and 5 females - 1781 mg/kg
5 males and 5 females - 1260 mg/kg
5 males and 5 females - 1596 mg/kg

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: deaths and abnormal clinical signs were noted 15 min after the administration of the test article, then at 1, 2 and 4 hours and then daily for the 14-day study period; the animals were weighed the day before the treatment, immediately before the treatment and at day 8 and 15 during the study period, and at the time of death from day 2 onwards.
- Necropsy of survivors performed: The animals that died during the study were necropsied as well as the surviving animals at the end of the 14-day study, which were killed by the means of overdosing with carbon dioxide.
- Other examinations performed: after necropsy the abdominal and thoracic cavities were opened and special attention was paid to the liver, heart, lungs and kidneys.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 292 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Bliss' method

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 280 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Litchfield and Wilcoxon' method

Mortality:

10% of the animals in the group treated with 1126 mg/kg died from day 2 onwards. 60% of the rats treated with 1260 mg/kg died from day 2 onwards. 60 % of the rats treated with 1411 mg/kg died from day 2 onwards. 100 % from the rats treated with 1596 mg/kg and 1781 mg/kg died from 2 onwards.

Clinical signs:

Subdued behaviour or prostration were noted in all the groups of animals at 2 and 4 hours after administration. Lethargy was observed in the animals treated with 1260 mg/kg or 1596 mg/kg. The surviving animals treated with 1126 mg/kg had normal behaviour by day 2 after administration, while the rats treated with 1260mg/kg or 1411mg/kg had normal behaviour by day 6. One of the surviving animals had diarrhorea (day 4 and 5) from the group treated with 1260 mg/kg and an animal treated with 1411 mg/kg showed piloerrection (day 3, 4 and 5).

Body weight:

Males treated with 1781 mg/kg and females treated with 1411mg/kg showed noticeably lower body weight than those in the control group. Males treated with 1411 mg/kg showed statistically lower mean body weight than those in the control group. The rest of the animals did not show any noticeable change in their body weight.

Gross pathology:

Animals that died during the study showed congested areas in the lungs, the stomach and the intestines. The animals examined at the end of the study showed adhesion between the liver, the stomach and the abdominal wall.

LD 50 for males:

Bliss' method: 1309 mg/kg

Litchfield and Wilcoxon's method: 1277 mg/kg

LD 50 for females:

Bliss' method: 1275 mg/kg

Litchfield and Wilcoxon' method: 1299 mg/kg

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, the LD50 for 1-Methyl-N,N',N''-tris(1-methylpropyl)silanetriamine was 1292 mg/kg bw (Bliss' method) or 1280 mg/kg bw (Litchfield and Wilcoxon's method) in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 280 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-05-10 to 1989-11-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Ico rat - OFA.SD. (IOPS Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo, France
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 206-250 g
- Fasting period before study: No information.
- Housing: individually in type FI polycarbonate cages.
- Diet (e.g. ad libitum): complete pelleted rat-mouse maintenance diet, ad libitum
- Water (e.g. ad libitum):softened and filtered, ad libitum
- Acclimation period: Seven days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-25
- Humidity (%): 50 - 91
- Air changes (per hr): At least 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: approximately 10% of the total body surface area.
- Type of wrap if used: Test article was kept in place by means of a semi-occlusive dressing composed of a perforated adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, using lukewarm water.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.39 ml/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2008 mg/kg bw/day

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 15 minutes after administration of the test substance, at 1, 2 and 4 hours, and then daily for the 14 day observation period. The animals were weighed immediately before application of the test material, then at day 8 and 15.
- Necropsy of survivors performed: yes, on day 15. The abdominal and thoracic cavities were opened and particular attention was paid to the liver, heart, kidneys, lungs and skin of the application area.
- Other examinations performed: clinical signs: changes in the fur, in the treated skin, the eyes, mucous membranes, respiratory system, circulated system, autonomic and central nervous system, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention. Body weight was recorded before application and at day 8 and 15.

Statistics:

The body weights of the animals were evaluated, for each sex, calculating the mean of the values obtained, the standard deviation, and the variation coefficient, which indicates the homogeneity of the data. No other statistics performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 008 mg/kg bw

Mortality:

No deaths.

Clinical signs:

There were no changes in behaviour or clinical signs in any of the treated animals.

Body weight:

There were no treatment-related effects on body weight.

Gross pathology:

There were no macroscopic findings that could be associated with treatment.

Other findings:

- Cutaneous examinations: According to the description of the study authors, 'a blackish aspect' of the cutaneous surface to the application area of the test article was noted in all the rats on day 2. Then the presence of superficial eschar formations was noted in all the rats from day 3 onwards and up to the end of the observation period. No presence of oedema was noted during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study conducted to OECD TG 402 and in compliance with GLP, the LD50 for 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine was >2008 mg/kg bw.

Executive summary:

SBA 52 was applied, once only, as supplied and at the dose level of 2008 mg/kg bw/day, by the cutaneous route under a semi-occlusive dressing, in the Sprague-Dawley rat (five/sex). Mortality and abnormal clinical signs were noted 15 minutes after application, then at 1, 2 and 4 hours, and then daily for the 14 day study period. All the animals were weighed immediately before the skin application of the test substance, and on day 8 and 15. A necropsy was performed for all the animals after the 14 day study period and the final observation. There were no deaths. A blackish aspect of the cutaneous surface to the application area of the test article was noted in all the rats on day 2. Then the presence of superficial eschar formations was noted in all the rats from day 3 onwards and up to the end of the observation period. No presence of oedema was noted during the study. The LD50 was greater than 2008 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 008 mg/kg bw

Additional information

The key acute oral toxicity study, conducted to the now deleted OECD 401 guideline and to GLP, reports an LD50 of 1280 mg/kg bw in rat, for 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (Hazleton, 1989.)

The doses administered were 1126, 1411, 1781, 1260 and 1596 mg/kg, with mortalities evident at all doses between days 2 and 3 of the 14 day observation period. 10% of the test animals died at the lowest dose, 60% of the rats died at 1260 and 1411 mg/kg bw, and all animals at the top two doses died.

The clinical signs included subdued behaviour, prostration and lethargy, occurring from day 2 until 6 days post-administration, and the effects were noted in all the animals. A decrease in the body weight of the surviving animals was observed. On necropsy, congested areas were observed in the lungs, stomach and intestines of animals that died during the course of the study. Adhesion between the liver, the stomach and the abdominal wall was noted in the animals examined at the last day (15) of the study.

A reliable supporting study was also available, which reports an LD50 of 789.70 mg/kg bw, supporting the findings of the key study (IPTP, 1979).

The key acute dermal toxicity study, conducted to OECD 402 and to GLP, reports an LD50 of >2008 mg/kg bw in rat, for 1 -methyl-N,N',N''-tris(1-methylpropyl)silanetriamine (Hazleton, 1989).

Following the cutaneous application of 2008 mg/kg bw of the tested material to male and female rats, there were no mortalities. No clinical signs were observed, with no changes in behaviour or body weight were observed. It was observed that the cutaneous surface of the application area appeared blackish, with superficial eschar formation noted in all the animals on days 2 and 3 respectively until the end of the 14-day study period. Oedema was not evident during the study period.

Justification for classification or non-classification

Based on the available data, 1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine is classified as Acute Toxicity Category 4, 'H302: Harmful if swallowed'. No classification for acute dermal toxicity is required according to Regulation (EC) No 1272/2008.