1,1,1,3,3,3-hexamethyldisilazane

Endpoint summary

Description of key information

In a skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5) did not cause significant irritation and was not corrosive to the rabbit skin (Dow Corning Corporation, 1993a).

In the key eye irritation study, which was conducted according to OECD Test Guideline 405 and in compliance with GLP, 1,1,1,3,3,3-hexamethyldisilazane was not irritating to rabbit eyes (Dow Corning Corporation, 1993b).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04.10.1993 to 12.10.1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton, Michigan, USA.
- Age at study initiation: No data
- Weight at study initiation: 2.98 - 3.09 kg
- Housing: Individually in conventional design stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days


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


IN-LIFE DATES: From: 04.10.1993 to 12.10.1993

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

Seven days (1, 24, 48, 72 hours and 7 days)

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Dorsal trunk
- % coverage: No data
- Type of wrap if used: The application site was covered with porous gauze dressing and then wrapped in a semi-occlusive fashion with a cotton bandage taped to the hair.


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

SCORING SYSTEM: The 4 point scale cited in the OECD guideline (404) was used. 

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

1.22

Max. score:

8

Reversibility:

fully reversible within: Seven days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed at the one-hour reading following the four hour exposure. Erythema was seen in two of the three animals following the four-hour exposure. Erythema was observed at 24, 48 and 72 hours in two rabbits.  All signs of irritation had subsided by the seventh day observation period. The third animal showed no signs of irritation during the study. 

Interpretation of results:

GHS criteria not met

Conclusions:

In a skin irritation study, conducted according to OECD Test Guideline 404 and in compliance with GLP, 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5) did not cause significant irritation and was not corrosive to the rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07.09.1993 to 06.12.1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Age:  Young male adult rabbits weighing between 2.7 and 2.85 kg
No further data - details taken from IUCLID 2008
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 2.7 to 2.85 kg
- Housing: Individually in stainless steel cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days


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: From: 26.10.1993 To: 29.10.1993

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

No washing

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not done

SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: Fluorescein stain was used at the 24, 48, and 72-hour readings. Eyes were examined by slit illumination for ocular changes of the cornea, iris (internal effects) and conjunctiva.

Irritation parameter:

overall irritation score

Time point:

24/48/72 h

Score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See Table 1. The test material caused slight conjunctival hyperemia in two animals and slight conjunctival chemosis in one animal at the 1 hour reading; these reactions had subsided at the subsequent readings (2 or 24 hours). The primary eye irritation score was calculated for the animals to be 0 (non-irritating).

Other effects:

A very slight immediate pain response was observed in all animals. 

Table 1 Mean irritation scores

Individual Tissue parameter	1 hour	2 hours	24 hours	48 hours	72 hours
Corneal Opacity	-	-	0	0	0
Iridial inflammation	0	0	0	0	0
Conjunctival irritation
Redness	0.7	0	0	0	0
Chemosis	0.3	0	0	0	0

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In a reliability score 1 eye irritation study, which was conducted according to OECD Test Guideline 405 and in compliance with GLP, 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3) was non-irritating to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the case of skin irritation, the most reliable study was selected as the key study.

Less reliable supporting studies were conducted under occlusive conditions and resulted in corrosive findings, which were considered to be attributable to increased hydrolysis of 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213 -668-5) and production of ammonia which is known to be corrosive to skin.

In the key skin irritation study (Dow Corning Corporation, 1993a) conducted according to OECD Test Guideline 404 and in compliance with GLP, 0.5 ml undiluted test substance was applied to one intact site of each animal (three New Zealand white rabbits), and the site was covered with porous gauze and then wrapped in a semi-occlusive cotton bandage (Dow Corning Corporation, 1993a). After a 4-hour exposure period the application site was washed with tap water. Skin reactions were scored at 1, 24, 48 and 72 hours and 7 days. No irritation was noted after 1 hour. Erythema was observed in 2/3 animals, at 24, 48 and 72 hours. All signs of irritation had reversed by day 7. The third animal showed no signs of irritation throughout the study. The primary dermal irritation score was calculated to be 1.22, and overall the conclusion was that the test substance was minimally irritating to the skin of rabbits, but not sufficient for classification.

The most reliable study available for eye irritation was selected as the key study. Additional less reliable eye irritation studies supported the findings of the key study.

In the key eye irritation study, which was conducted according to OECD Test Guideline 405 and in compliance with GLP, 1,1,1,3,3,3-hexamethyldisilazane was not irritating to rabbit eyes (Dow Corning Corporation, 1993b). Following single instillation of undiluted test material into the eyes of three New Zealand white rabbits, a very slight immediate pain response was observed in all animals. The test material caused slight conjunctival hyperaemia in two animals and slight conjunctival chemosis in one animal at the 1-hour reading. These reactions had subsided at the subsequent readings (2 and 24 hours). The cornea, iris, conjunctivae and chemosis readings for all the animals were 0 at 24, 48 and 72 hours.

Justification for classification or non-classification

Based on the available data 1,1,1,3,3,3-hexamethyldisilazane (CAS 999-97-3, EC 213-668-5) does not require classification for skin or eye irritation according to Regulation (EC) 1272/2008.