Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
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

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: transparent liquid

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levelsopen allclose all
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.

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 is 907.45 mg/kg for 1,1-dimethyl-N,N'-bis(1-methylpropyl)silanediamine.