N,N',N''-tricyclohexyl-1-methylsilanetriamine

Endpoint summary

Description of key information

The key acute oral toxicity study for N,N',N''-Tricyclohexyl-1-methylsilanetriamine reports an LD50 of 637 mg/kg bw. It was conducted according to OECD Test Guideline 401 (now deleted) and in compliance with GLP (Hazleton, 1989).  

The key acute dermal toxicity study for N,N',N''-tricyclohexyl-1-methylsilanetriamine reports an LD50 of 1594 mg/kg bw. It was conducted according to OECD Test Guideline 402 and in compliance with GLP (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

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 - OFA.SD. (IOPS Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffra-Credo, France
- Age at study initiation: between 5 and 7 weeks old
- Weight at study initiation: from 125 g to 165 g
- Fasting period before study: 16-17 hours of water only regime
- Housing: housed by sex and in groups of 5 in type MI polycarbonate cages (interior dementions 365 x 225 x 180)
- Diet: complete pelled rat-mouse maintenance diet ad libitum
- Water: softened and filtered mains drinking water ad libitum
- Acclimatisation period: 9 days before the start of the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 27
- Humidity (%): 40 to 70% R.H.
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 893 mg/kg

Doses:

Four groups (2 to 5) of 5 males and 5 non-pregnant females. Group 2 treated with 566 mg/kg, group 3 treated with 710 mg/kg, group 4 treated with 893 mg/kg and group 5 treated with 634 mg/kg.

No. of animals per sex per dose:

5 males and 5 non-pregnant females.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: any deaths and abnormal clinical signs were notes 15 minutes after the administration, then at 1, 2 and 4 hours and then daily for the 14 day study period; the animals were wighed the day before the treatment, immediately before administration of the test article, at days 8 and 15 as well as at the time of death.
- Necropsy of survivors performed: on the last day of the study (day 15) all surviving rats were killed by means of overdosing with carbon dioxide. The abdominal and thoracic cavities were opened and particular attention was pain to the liver, heart, kindneys and lungs.
- Other examinations performed: the daily observations performed included changes in the skin and fur, the eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous system as well as somato-motor activity and behaviour. Shivering, convultions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

642 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Bliss' method

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

637 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Lichfield and Wilcoxon' method

Mortality:

By day 15 of the study, 30% from the group of males and females treated with 566 mg/kg were dead, first death recorded 4 hours after administration. The same effect was observed in the group of males and females treated with 634 mg/kg. 80% of males and females treated with 710 mg/kg were
dead and 100% mortality was observed for the group (males and females) treated with 893 mg/kg of the tested article.

Clinical signs:

Subdued behaviour or prostration were noted in animals treated with 566 mg/kg, 634 mg/kg and 710 mg/kg and 893 mg/kg. A female, treated with 566 mg/kg, was showing prostration until day 5 and at day 6 was found dead.Convulsions or tremors were observed in rats treated with 710 mg/kg
or 893 mg/kg. All surviving animals (from each group) recovered normal behaviour by day 3. 4 and 6 respectively.

Body weight:

Males of groups 2 and 5 had noticeably lower body weight than those in the control group, while no such observation could be noted in the female
groups 2 and 5.

Gross pathology:

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

LD 50 for males:

Bliss' method: 640 mg/kg

Lichfield and Wilcoxon' method: 636 mg/kg

LD 50 for females:

Bliss' method: 643 mg/kg

Lichfield and Wilcoxon' method: 639 mg/kg

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was reported to be 642/637 mg/kg bw in a reliable study, conducted according to OECD test guideline 401 (now deleted) and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

637 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:

10 May 1989 until 02 February 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

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

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffra-Credo, France
- Age at study initiation: between 6 and 8 weeks old
- Weight at study initiation: from 206 g to 259 g
- Fasting period before study: no
- Housing: housed individually in type FI polycarbonate cages
- Diet: complete pelled rat-mouse maintenance died ad libitum
- Water: softened and filtered mains drinking water ad libitum
- Acclimation period: 7 days before the start of the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 44 to 90% R.H.
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the trunk
- % coverage: 10% of the total body surface area
- Type of wrap if used: semi-occlusive dressing (perforated adhesive band and elastic bandage)

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


TEST MATERIAL
- Constant volume or concentration used: no.

Duration of exposure:

24 hours

Doses:

Four groups of 5 males and 5 non-pregnant females were treated with 1594mg/kg, 2006 mg/kg, 2515 mg/kg and 1267 mg/kg respectively.

No. of animals per sex per dose:

5 males and 5 non-pregnant females

Control animals:

yes

Details on study design:

Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weight observation prior to the treatment, at days 8 and 15
- Necropsy of survivors performed: yes. At day 15 al surviving rats were killed my means of overdosing with carbon dioxide. Particular attention was paid to liver, heart, kindneys and lungs.
- Other examinations performed: any deaths and clinical observations were noted at 15 minutes after administration, then at 1,2 and 4 hours, and
then daily for 14 days after administration with detaled description of the clinical signs. The daily observations included changes in the fur, in the
treated skin, the eyes, mucous membranes, respiratory system, circulatory syste, autonomic and central nervous system as well as somato-motor
activity and behaviour.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 594 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed in 10% from the female group treated with 1267 mg/kg from day 4 onwards, in 50% from the female group treated with
1594 mg/kg from day 2 onwards, in 90% from both female and male group treated with 2006 mg/kg from dat 2 onwardsand in 100% in the
female and male group treated with 2515 mg/kg from day 2 onwards.

Clinical signs:

Prostration or lethargy was observed in all the animal groups on day 2 from the study. On day 3 rats treated with 1267 mg/kg and 1594 mg/kg had
normal behaviour. One female from the group treated with 2006 mg/kg was presenting with lethargy at days 3 and 4 and one male from the same
group was presenting with prostration on day 3. On day 5 all the surviving rats had norml behaviour.

Body weight:

Body weight changes in group 2-5 males were identical to the those in the control group. The body weigh changes of females from group 5 were
signifiantly lower to those of the control group.

Gross pathology:

The macroscopic abnormalities observed were characterized by congestive aspect of the lungs of the cutaneous and sub-cutaneous tissues in the
animals dead during the study and by an oedema of the sub-cutaneous tissues in the animals killed at the end of the study as well as purple colour of
the tissue in the group treated with 2515 mg/kg.

Other findings:

Epidermal necrosis was observed in all the animals. Dryness of the skin in groups 2-3 on days 2 to 3, and in group 5 on days 2 to 4. Superficial
eschar formations were observed in groups 2-3 from day 4 and group 5 from day 5 until day 15 from the study.

The estimated values of LD50for males and females separately are:

1594 mg/kg < LD50 by the cutaneous route, in the male rat < 2006 mg/kg

1267 mg/kg < LD50 by the cutaneous route, in the female rat < 1594 mg/kg.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 was reported to be 1594 mg/kg bw in a reliable study, conducted according to OECD guideline and in compliance with GLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 594 mg/kg bw

Additional information

The key acute oral toxicity study reports an LD50 of 637 mg/kg bw. This study was conducted according to OECD Test Guideline 401 (now deleted) and in compliance with GLP, for N,N',N''-Tricyclohexyl-1-methylsilanetriamine (Hazleton, 1989).

The doses, 566 mg/kg bw, 634 mg/kg bw, 710 mg/kg bw and 893 mg/kg bw, were administered by gavage to male and female rats. Mortalities were evident at all doses, from 4 hours until the end of the 14-day study period. Subdued behaviour or prostration were noted in all the animals. Convulsions or tremors were observed in rats treated with 710 mg/kg bw or 893 mg/kg bw of the test material. All the animals recovered normal behaviour by day 6. A noticeable decrease in body weight in 10 out of 20 males was noted during the study period. At necropsy, adhesion between the liver, the stomach and the abdominal wall was observed.

A reliable supporting study was also available, which reports an LD50 of 505 mg/kg bw, supporting the findings of the key study (IPT, 1979).

The key acute dermal toxicity study reports an LD50 of 1594 mg/kg bw. This study was conducted according to OECD Test Guideline 402 and in compliance with GLP, for N,N',N''-tricyclohexyl-1-methylsilanetriamine (Hazleton, 1989).

The doses, 1267 mg/kg bw, 1594 mg/kg bw, 2006 mg/kg bw, 2515 mg/kg bw, were applied to the skin of male and female rats. Mortalities were evident at all doses, from 2 hours until the end of the 14-day study period. Prostration or lethargy was observed in all the animals. Normal behaviour was recovered by day 5 in the surviving animals. Significant decrease in body weight was observed in 5 out of 20 females. At necropsy, oedema as well as purple colour of the sub-cutaneous tissues were noted. Epidermal necrosis, dryness of the skin and superficial eschar formations were also observed.

Justification for classification or non-classification

Based on the available data, N,N',N''-tricyclohexyl-1-methylsilanetriamine is classified as Acute Oral Toxicity Category 4, 'H302: Harmful if swallowed', and Acute Dermal Toxicity, Category 4, 'H312: Harmful in contact with skin', according to Regulation (EC) No. 1272/2008.