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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:
03.06.80 to 05.08.80
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Study was conducted prior to the adoption of OECD test guidelines and GLP
GLP compliance:
no
Remarks:
Pre-GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Verteiler H (hexamethyldisilazan).
No further details available.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: Yes, but period not given.
- Housing: Groups of 5 in Makrolon Type II cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ±2
- Humidity (%): 60 ±5
- Air changes (per hr): about 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 03.06.80 To: 05.08.80

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.5 ml/kg bw
Doses:
0.1, 1.0, 1.2, 1.4 and 1.5 ml/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observations and weighing once per week.
- Necropsy of survivors performed: yes
- Other examinations performed: Not clear
Statistics:
The acute oral LD50 was determined by probit-regression analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1.1 mL/kg bw
95% CL:
>= 1 - <= 1.2
Sex:
male/female
Dose descriptor:
LD50
Effect level:
851 mg/kg bw
Mortality:
See Table 1.
Clinical signs:
At doses of 1.0 ml/kg bw and above paralysis of hind limbs, sedation, anaesthesia and poor general condition were observed.
Body weight:
Reduced body weights were recorded at doses of 1.0 m/kg bw and above.
Gross pathology:
Redness of the stomach mucosal membrane among animals that died during the study and those sacrificed at the end of the observation period.
Other findings:
None reported

Any other information on results incl. tables

Table 1 Summary of mortality

 Dose (ml/kg bw)  Dead/dosed  Days to death  Mortality (%)
 Males         
 0.1  0/5  -  0
 1.0  2/5  3  40
 1.2  1/5  2  20
 1.4  5/5  4  100
 1.5  5/5  2 100 
 Females         
 0.1  0/5  -  0
 1.0  2/5  40
 1.2  4/5  4  80
 1.4  4/5  7  80
 1.5  5/5  2  100


 

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a pre-GLP acute oral toxicity study (reliability score 2) conducted using a protocol that was comparable to the now deleted OECD 401, the LD50 for hexamethyldisilazane was 1.1 ml/kg bw.
Executive summary:

In a pre-GLP acute oral toxicity study (reliability score 2) conducted using a protocol that was comparable to the now deleted OECD 401, Sprague-Dawley rats (5/sex/dose) were exposed by oral gavage to hexamethyldisilazane at doses of 0.1, 1.0, 1.2, 1.4 and 1.5 ml/kg bw. The animals were then observed for 14 days for signs of toxicity. Animals were weighed before dosing and on day 7 and 14 of the observation period. At doses of 1.0 ml/kg bw and above paralysis of hind limbs, sedation, anaesthesia, poor general condition and reduced body weight were observed. Necropsy revealed redness of the stomach mucosal membrane among animals that died during the study and those that were sacrificed at the end of the observation period. No deaths or signs of toxicity were observed at the lowest dose. There were 4/10, 5/10 (1 female and 4 males), 9/10 and 10/10 deaths at 1.0, 1.2, 1.4 and 1.5 ml/kg bw. The LD50 was calculated to be1.1 ml/kg bw/day.