N-sodiohexamethyldisilazane

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information from published industry source (USEPA), minor limitations in design and/or reporting but otherwise adequate for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The acute oral toxicity was determined in rats employing a modified procedure in "Appraisel of the Safety of Chemicals in Foods, Drugs and Costmetics, Published by the Association of Food and Drug Officials of the U.S. (1959)".

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Long-Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Fasting period before study: 18 hours
- Diet: ad libitum
- Water: ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

1% (v/v)

Doses:

0.05, 0.1, 0.25, 0.5, 0.9, 0.95, 1, 2.5 mL/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Other examinations performed: clinical signs

Statistics:

The acute oral toxicity LD50 for rats was calculated accoring to the method of Miller and Tainter (Proc. Soc. Med. 57, 261 (1944).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 mL/kg bw

Based on:

test mat.

Mortality:

- No mortality observed in animals exposed to 0.05, 0.1, 0.25, 0.5 or 0.9 mL/kg.
- 7 out of 10 animals exposed to 0.95 mL/kg died, within 2 days after exposure.
- 6 out of 10 animals exposed to 1 mL/kg died, within 2 days after exposure.
- All animals exposed to 2.5 mL/kg died, within 2 days after exposure.

Clinical signs:

other: - Decreased activity and ataxia observed in animals exposed to 0.05, 0.1 or 0.25 mL/kg. - Decreased activity or sedation, ataxia or incoordination, urinary incontinence, decreased respiration observed in animals exposed to 0.5 mL/kg. - Sedation, incoordin

Gross pathology:

- Lungs pinkish grey colour, liver mottled and spleen granular in animals exposed to 0.05 mL/kg.
- Lungs and liver mottled and spleen granular in animals exposed to 0.1 mL/kg.
- Liver and kidneys mottled, and granular spleen in animals exposed to 0.25 mL/kg.
- Lungs puffy and mottled, and spleen granular in animals exposed to 0.5 mL/kg.
- Lung mottled, liver dark in colour, spleen pale and granular, kidneys pale and mottled in animals exposed to 0.9 mL/kg.
- Lungs mottled, spleen granular, kidneys pale and mottled, and skin vascularized in animals exposed to 0.95 mL/kg.
- Lungs, liver and kidneys mottled, spleen granular, and skin vascularized in animals exposed to 1 mL/kg.
- Lungs mottled, liver dark, spleen granular, and kidneys pale and mottled in animals exposed to 2.5 mL/kg.

Interpretation of results:

harmful

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

LD50 was calculated based on an assumed density of 1000 mg/mL.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information from published industry source (USEPA), limitations in design and/or reporting but otherwise adequate for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Two Sprague-Dawley rats per sex per dose group were exposed by inhalation to the test substance for 4 hours. After an observation period of 14 days, animals were necropsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 250 g
- Housing: individually, stock cages
- Diet: ad libitum, standard laboratory rat diet from Wayne Lab Blox, Allied Mills, Chicago, Illinois
- Water: ad libitum
- Acclimation period: 5 days

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass inhalation chamber
- Exposure chamber volume: 5.5 liter
- System of generating vapour: vapours were produced by bubbling dried metered arid thorugh the undiluted test material. Additional dried metered air was mixed with the vapour stream to achieve the desired concentration levels.

POSITIVE CONTROL
- No. of animals: 4 groups of 2 animals per sex per dose
- Positive control compound: 10% ammonium hydroxide solution
- Concentrations: 8.5, 18.9, 33, 72.5 mg/L air

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

ca. 4 h

Remarks on duration:

Except 60.5 and 94.3 mg/L dose group, which were exposed 110 and 70 min., resp.

Concentrations:

5.6, 19, 30.4, 60.5, 94.3 mg/L air

No. of animals per sex per dose:

2

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The mortality data were analyzed statistically, employing the technique of Litchfield and Wilcoson (J.T. Litchfield, Jr. and F. Wilcoxon, "A Simplified Method of Evaluating Dose-Effect Experiments." J. Pharm. & Exp. Ther., Vol 96, No. 2, pp. 99-113, 1949.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

10.3 mg/L air

Based on:

test mat.

95% CL:

6.4 - 16.5

Exp. duration:

4 h

Mortality:

- No mortality observed in animals exposed to 5.6 mg/L
- All animals exposed to 19, 30.4, 60.5, 94.3 mg/L died, within 70 minutes to 48 hours after exposure

Clinical signs:

other: - Hypoactivity, hyperpnoea and ataxia were observed in animals exposed to 30.4, 60.5 or 94.3 mg/L, after 4 to 14 minutes of exposure. Sedation was noted at the 10 to 21 minute point. Sedation and hyperpnoea persisted until death. - Hypoactivity was observ

Gross pathology:

- Necroscopy revealed mild lung haemorrhage in animals exposed to 19, 30.4, 60.5 or 94.3 mg/L hexamethyldisilazane.

Interpretation of results:

harmful

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

10 300 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information from published industry source (USEPA), limitations in design and/or reporting but otherwise adequate for assessment No GLP, no details on analytical purity

Qualifier:

no guideline followed

Principles of method if other than guideline:

Five New-Zealand White rabbits per sex per dose group were exposed by occlusive dermal application to the test substance for 24 hours. During the observation period of 14 days animals were examined for mortality, local reactions and clinical signs.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg
- Diet: ad libitum, commerial diet
- Water: ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

Males: 0.5, 0.71, 1.0 mL/kg; Females: 0.25, 0.5, 1.0, 4.0, 16.0 mL/kg

No. of animals per sex per dose:

4 (2 in at 4 and 16 mL/kg dose levels)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50s were calcuted by the Thompson method (Thompson WR,1947.Bact.Rev.11;115-145)

Sex:

male

Dose descriptor:

LD50

Effect level:

0.76 mL/kg bw

Based on:

test mat.

95% CL:

0.62 - 0.94

Sex:

female

Dose descriptor:

LD50

Effect level:

0.71 mL/kg bw

Based on:

test mat.

95% CL:

0.46 - 1.08

Mortality:

All animals died between 2 hours and 3 days after exposure in the 1, 4, and 16 mL/kg dose groups. One animal died in the 0.71 mL/kg dose group after three days (males). No animals died in the 0.25 mL/kg (male) and 0.5 mL/kg (males and females)

Clinical signs:

other: Erythema, edema and necrosis were noted in all dose groups. In males signs included prostrations (0.71 and 1 mg/kg) and sluggishness (0.5 mL/kg). In females signs included discomfort (4 and 16 mL/kg), lethargy and slow and shallow breathing (1 and 4 mL/kg

Gross pathology:

- Males: 0.5 mL/kg: Trachea red (1/4), liver with tan foci (coccodiae; 1/4); 0.71 mL/kg: nothing remarkable; 1.0 mL/kg: Lung and liver dark (1/4), trachea red (2/4), small testis (1/4) bladder distended filled with red/yellow fluid (1/4)
- Females: 0.25 mL/kg: Lungs with dark patches (2/4), trachea with slight redness along mucosal surface (1/4); 0.5 mL/kg: lung and trachea red (1/4); 1.0 mL/kg: lungs mottled dark red (2/4), trachea dark red (1/4); 4.0 mL/kg: lungs with dark red patsches; 16.0 mL/kg: nothing remarkable.

Interpretation of results:

toxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Additional information

Sodium-HMDS has not been tested. However, data is available for HMDS, showing the following:

acute oral:              LD50 = 1 ml/kg (US EPA, 1992), LD50 = 813 mg/kg (US EPA, 1965), LD50 = 1.1 ml/kg (US EPA, 1988)                               and LD50 =1.83 ml/kg (male) and 2.46 ml/kg (female, US EPA, 1993)

acute inhalation:      LC50 = 10.3 mg/L (4h, US EPA, 1995), LC50 > 1016 ppm  (1 h, US EPA, 1993), LC50 > 193 mg/L (1 h,                               US EPA, 1993)

acute dermal:         LD50 = 1350 mg/kg (US EPA, 1965), LD50 > 1000 mg/kg (US EPA, 2013), LD50 = 0.73 ml/kg (US EPA,                               1993)     

Justification for classification or non-classification

No study is available with sodium-HMDS. However, a variety of studies is availbale for HMDS (CAS 999-97-3). HMDS is moderately toxic for all three routes of exposure. Assuming that HMDS has similar properties, it is classified as acute toxic category 4 for all three routes of exposure, H302, 312, 332 according to Regulation 1272/2008 (CLP) and R20/21/22 according to Directive 67/548/EEc (DSD)