Registration Dossier

Administrative data

Description of key information

The key study for acute oral toxicity (Bayer, 1988) was one of two reliability score 2 studies. The most recent of these was selected as the key study; however, these studies gave very similar results. Many reliability score 4 studies are available to support the LD50 in the key study. There was only one reliable study for the dermal route (Bushy Run Research Centre, 1981); however, supporting reliability 4 studies gave similar results. For the inhalation route the most reliable study, which had a reliability score 1, was selected as the key study (Dow Corning Coporation, 2007).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
851 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
10 008 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
547 mg/kg bw

Additional information

In the key acute oral toxicity study (Bayer, 1980) similar to the now deleted OECD 401, Wistar rats were given a single gavage dose of hexamethyldisilazane which resulted in clinical signs including paralysis of hind limbs, sedation, anaesthesia and poor general condition. Redness of the stomach mucosal membrane among animals that died was also noted. An LD50 of 1.1 mL/kg bw (equivalent to 851 mg/kg bw, based on a density of 0.774 g/cm3) was defined.

In the key acute dermal study (Bushy Run Research Center, 1981c), which was similar to OECD 402, New Zealand white rabbits were exposed to the test substance under an occlusive dressing for 24 hours which resulted in clinical signs of sluggishness, prostration, lethargy, slow and shallow breathing, discomfort and skin corrosion. . The LD50 was defined 547 mg/kg bw in females and 589 mg/kg bw in males (based on a density of 0.774g/m3).

In the inhalation route the key study (Dow Corning Corporation, 2007) was conducted according to OECD 403, whole-body, for six hours the LC50 was 1516 ppm (10008 mg/m3). Clinical observations consisted of inactivity, lethargy, shallow and laboured breathing, lacrimation, cold to touch and soiling (urogenital and eyes). There were no toxicologically significant necropsy findings.


Justification for selection of acute toxicity – oral endpoint
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Justification for selection of acute toxicity – inhalation endpoint
The study was conducted in accordance with an appropriate guideline and in compliance with GLP.

Justification for selection of acute toxicity – dermal endpoint
The study was conducted according to a test protocol that is comparable to the appropriate OECD test guideline. It was not compliant with GLP.

Justification for classification or non-classification

Based on the available data Hexamethyldisilazane requires classification as acute toxic 4 (oral) (H302: Harmful if swallowed), acute toxic 3 (dermal) (H311: Toxic in contact with skin) and acute toxic 4 (vapour) (H332: Harmful if inhaled) according to Regulation (EC) 1272/2008.