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Toxicological information

Acute Toxicity: oral

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine
EC Number:
253-634-7
EC Name:
1-methyl-N,N',N''-tris(1-methylpropyl)silanetriamine
Cas Number:
37697-65-7
Molecular formula:
C13H33N3Si
IUPAC Name:
{bis[(butan-2-yl)amino](methyl)silyl}(butan-2-yl)amine
Test material form:
other: colourless liquid

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levelsopen allclose all
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.

Any other information on results incl. tables

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

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, 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.

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