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Diss Factsheets

Administrative data

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
 Conjunctival irritation               
 Redness  0.7  0  0  0  0
 Chemosis  0.3  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.