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Administrative data

Description of key information

Based on the available information from the key acute oral toxicity study the LD50 for 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine was concluded to be 907.45 mg/kg bw. The study was conducted according to OECD test guideline 401 and in compliance with GLP (Pharmakon, 1993).

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:
21/12/1992 to 18/03/1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(now deleted)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: Ico: OFA.SD. (IOPS Caw)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, France
- Age at study initiation: 5 to 7 weeks old
- Weight at study initiation: males 130-230 g and females 120-180 g
- Fasting period before study: 15-20 hours before treatment
- Housing: in an air conditioned building. Animals kept in group of 5 of the same sex in type MI polycarbonate cages.
- Diet (e.g. ad libitum): pelleted complete diet ad libitum
- Water (e.g. ad libitum): filtered mains drinking water ad libitum
- Acclimation period: 5 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70% R.H.
- Air changes (per hr): minimum 8 air changes 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: 2000 mg/kg

Doses:
20-30 males and females were separated in 4 groups and treated with 567 mg/kg, 689 mg/kg, 826 mg/kg and 1004 mg/kg.
No. of animals per sex per dose:
20 to 30 males and 20 to 30 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals observed 15 minutes after the administration, then at 1, 2 and 4 hours, then daily for the 14-day study. The body weight was measured a day before the treatment, immediately before the treatment and on day 8 and 15, and on the day of the death.
- Necropsy of survivors performed: at day 15 surviving animals were killed by overdosing with carbon dioxide and necropsied. Necropsy was performed to the dead animals during the study. Examination was performed of the external surface, all orifices, the thoracic, abdominal and pelvic cavities and viscera.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: animals surviving 24 hours or more after administration of the testing article, organs with macroscopic lesions will be kept in fixative until agreement reached to be examined by a pathologist.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
907.46 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Bliss' method
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
907.45 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Litchfield and Wilcoxon's method
Mortality:
The group treated with 689 mg/kg of the tested article showed 10 % mortality. The ones treated with 826 mg/kg - 30% mortality and those treated with 1004 mg/kg - 100 % mortality.
Clinical signs:
Subdued behaviour for the first 3 days of the study was observed in all the groups of animals. Abdominal distension was observed in groups treated with 689 mg/kg, 826 mg/kg and 1004 mg/kg from day 7 until day 15 from the study.
Body weight:
A slight decrease was observed in the body weight of the treated males when compared to the control group, while there was no significant change in the body weight of females.
Gross pathology:
Adhesion was observed between the stomach and the abdominal wall, liver and the abdominal wall, liver and the stomach, stomach and the spleen in all surviving animals. The rats that dies before the end of the observation period had stomachs distended by a reddish liquid and very congested intestines.
Other findings:
- Other observations: Some of the dead individual before the end of the observation period had congested stomach, autolysed alimentary canal and pale liver.
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 is 907.45 mg/kg for 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
907.45 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

In the key study for acute oral toxicity, gavage administration of test substance at dose levels of 567, 689, 826 and 1004 mg/kg bw to groups of five male and five female rats resulted in mortality levels of 0, 10, 30 and 100% respectively (Pharmakon, 1993). Mortalities occurred from Day 1 (4 hours) to day 3, depending on the dose. Clinical signs observed included subdued behaviour for the first 3 days of the study in all the groups of animals. Abdominal distension was observed in groups treated with 689, 826 and 1004 mg/kg bw from day 7 until day 15 from the study.

At necropsy, the animals that survived until study completion showed congested areas in the stomach and intestines. The animals that died during the study showed adhesion between the liver, abdominal wall, stomach, spleen and intestines.

The LD50 was calculated to be 907.45 (95% confidence interval 797.35<LD50<1032.74).


Justification for classification or non-classification

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