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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
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:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1,1,3,3,3-hexamethyldisilazane
EC Number:
213-668-5
EC Name:
1,1,1,3,3,3-hexamethyldisilazane
Cas Number:
999-97-3
Molecular formula:
C6H19NSi2
IUPAC Name:
bis(trimethylsilyl)amine
Details on test material:
- Name of test material (as cited in study report): Hexamethyldisilazane; Organofunctional Silane A-166; 1,1,1,3,3,3-hexamethyldisilazane.


No further details available

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 2-3 Kg
- Fasting period before study: No data
- Housing:No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: Impervious sheet


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Males: 1.0, 0.71 and 0.5 ml/kg bw; females: 16.0, 4.0, 1.0, 0.5 and 0.25 ml/kg bw
- Concentration (if solution): Undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
1.0, 0.71, and 0.50 mL/kg bw (770, 550, and 385 mg/kg bw based on a density of 0.77 g/cm3) in males and 16.0, 4.0, 1.0, 0.5, and 0.25 mL/kg bw (12,320, 3080, 770, 385, 193 mg/kg bw based on a density of 0.77 g/cm3) in females
No. of animals per sex per dose:
Four (except 16 and 4 ml/kg bw levels used two females each)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made daily. Weights were measured before dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
LD50s were calculated using the 'moving average method'.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
585 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
544 mg/kg bw
Based on:
test mat.
Mortality:
Males: 4/4, 1/4 and 0/4 at 1.0, 0.71 and 0.5 ml/kg bw, respectively.
Females: 2/2, 2/2, 4/4, 0/4 and 0/4 at 16.0, 4.0, 1.0, 0.5 and 0.25 ml/kg bw, respectively.
Clinical signs:
other: See Table 1
Gross pathology:
See Table 1
Other findings:
See table 1

Any other information on results incl. tables

Table 1 Summary of mortality, clinical and necropsy findings.

 Group (ml/kg bw)  Number of deaths/total exposed  Time to death (d)  Clinical observations  Necropsy findings
 Males            
 0.5  0/4  -  Sluggishness on Days 1 and 2 (2/4), skin erythema, edema, necrosis on Day 1 and desquamation by Day 14.  Trachea red (1/4), liver with tan foci (coccodiae; 1/4)
 0.71  1/4  3 Prostration in one animal, skin erythema and necrosis, and scabs by Day 14.  Nothing remarkable
 1.0  4/4  1, 1, 2, 3 Prostration in two animals, skin erythema, edema and necrosis Lung & liver dark (1/4), trachea red (2/4), bladder distended filled with red/yellow liquid (1/4)
 Females            
 0.25  0/4  - Capillary injection, erythema, necrosis, spots of ecchymosis on Day 1, desquamation, scabs at 14 days.  Lungs mottled dark red (2/4) and trachea slight redness along mucous lining (1/4)
 0.5  0/4  -  Sluggishness on Day 1, skin erythma, edema and necrosis on Day 1 with desquamation and scabs by Day 14.  Lungs and trachea dark red (1/4)
 1.0  4/4  1, 1, 1, 3 Lethargy, slow and shallow breathing (1 hour), skin erythema and necrosis  Lungs mottled dark red (2/4) and trachea dark red (1/4)
 4.0  2/2  1, 1 Signs of discomfort, lethargy slow and shallow breathing (30 mins), skin erythema and necrosis  Lungs with dark red patches
 16.0  2/2  0, 0 (within 2 hours) Signs of discomfort, skin erythema and necrosis  Nothing remarkable


Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study conducted according to a protocol that was comparable to OECD Test Guideline 402, but without information on GLP compliance, the LD50s for 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3) was concluded to be 544 mg/kg bw in females and 585 mg/kg bw in males (based on density of 0.77 g/cm3).