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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30.08.2006 to 17.07.2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Exposure period of six hours.

GLP compliance:

yes

Test type:

other: Similar to OECD 403

Limit test:

no

Test material

Test material information

Constituent 1

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage
- Age at study initiation: ≥10 weeks
- Weight at study initiation: Males: ≥223 g. Males: ≥347 g
- Fasting period before study: No
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Six/seven days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 32-64
- Air changes (per hr): 12.1 to 17.1
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 05.10.2006 To: 03.01.2007

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Test substance vapour was generated using a heated stainless steel J-tube containing a column of stainless steel beads into which test substance was metered.
- Exposure chamber volume: 450 litre
- Method of holding animals in test chamber: None
- Source and rate of air: Building aor was passed through a Nash Air Compressor
- Method of conditioning air: Compressed air was passed through a series of filters to remove contaminants.
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: No data


TEST ATMOSPHERE
- Brief description of analytical method used: Chamber atmosphere was analysed using a Varian 3400 gas chromatograph equipped with a flame ionization detector.
- Samples taken from breathing zone: No data

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Chamber atmosphere was analysed using a Varian 3400 gas chromatograph equipped with a flame ionization detector.

Duration of exposure:

6 h

Concentrations:

Target: 900, 1200 and 3450 (5.9, 7.8 and 22.6 mg/L); Nominal: 913, 1242, and 3755 ppm; Measured: 885, 1167 and 3400 ppm

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (animals killed on Day 15)
- Frequency of observations and weighing: Daily observations. Body weight measured on days 1 (first day of exposure), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: None

Statistics:

The mean lethal nominal chamber concentration (LC50), 95% confidence interval and approximate slope of the dose response curve were calculated using a SAS/STAT Spearman-Karber analysis. Means and standard deviations were determined for other data as appropriate.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1 516 ppm

Exp. duration:

6 h

Remarks on result:

other: equivalent to 10000 mg/m3

Mortality:

All animals on the 3755 ppm group died during the latter part of the six-hour exposure. In the 1242 ppm group 50% of the animals died prior to the scheduled terminal sacrifice. No animals died in the 913 ppm group.

Clinical signs:

other: There were no signs of toxicity before death in the animals of the highest dose group. In the lowest dose group clinical observations were: inactivity, lacrimation, eye lids partially closed, cold to the touch, muscles soft/limp, respiration slow/noisy an

Body weight:

Body weight gains for 913 ppm group averaged approximately 12%, while those for the  surviving animals in the 1242 ppm group averaged approxiately -1% over the 15 day observation period.

Gross pathology:

In the 3755 ppm group, five animals (three females and two males) presented with liver congestion, one of which also presented with spleen congestion, and two animals (males) presented with intestine (jejunum) congestion.  This represents a non-specific finding that indicates some increased circulation to the organ.  The remaining three animals showed no visible lesions.  All of the animals in this group died during the exposure.  In the 913 ppm group, one male animal presented with kidney foci depressed (minimal) and the remaining animals showed no visible lesions.  The minimal focal depressions in the kidneys of the one male represent a common spontaneous finding with no toxicological significance.  All of the animals in this group were necropsied at the scheduled terminal sacrifice on day 15.  In the 1242 ppm group, three animals (one male and two females), found dead on days 4 or 5, presented with decreased stomach ingesta, two of which (females) also presented with liver discoloration (pale).  The decreased stomach ingesta indicates that the animals were too sick to eat.  Pale livers can be caused by lipidosis or from autolysis; since these animals were found dead, it is assumed the latter. The two other animals which were found dead (on day 2) and the remaining animals which were necropsied at the scheduled terminal sacrifice showed no visible lesions.  

Other findings:

None reported

Any other information on results incl. tables

Table 1 Mortality results and time to death.

Sex	Exposure concentration (ppm)	Number of deaths	Time to death
Male	3755	5/5	During exposure period
	1242	3/5	Two on Day 2 and one on Day 5
	913	0/5	No deaths
Female	3755	5/5	During exposure period
	1242	2/5	One on each of Days 4 and 5
	913	0/5	No deaths

                        

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute inhalation toxicity study (reliability score 1) conducted according to OECD Test Guideline 403 and in compliance with GLP, the LC50 value for 1,1,1,3,3,3-hexamethyldisilazane in the Sprague-Dawley rat was determined to be 1516 ppm (equivalent to 10000 mg/m³).