Registration Dossier

Administrative data

Description of key information

The 90-day OECD 413 study with hexamethyldisilazane (Harlan, 2014) conducted by nose-only inhalation was selected as the key study and identified the NOAEC as 2640 mg/m3 (400 ppm), the highest concentration tested. An OECD 422 (Dow Corning Corporation, 2008) conducted by the inhaled route identified the NOAEC as 660 mg/m3. Two other studies available for the inhalation route gave similar NOAECs. Hexamethyldisilazane is rapidly hydrolysed in contact with moisture releasing trimethylsilanol and ammonia. There is an OECD 422 study available on the hydrolysis product, trimethylsilanol (WIL Research Laboratories, 2008), which indicates some of the adverse effects of Hexamethyldisilazane can be attributed to other hydrolysis product, ammonia. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
2 640 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 640 mg/m³
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key repeat dose study OECD 413 study (Harlan, 2014), Sprague-Dawley rats were exposed, nose-only, to hexamethyldisilazane vapour 6 hours a day, 5 days a week for 13 weeks, followed by a 4 -week recovery period, at 0, 25, 75 or 400 ppm. Clinical signs of decreased activity and ataxia, minor effects on body weight and food consumption and minor changes in haematology, clinical chemistry and urinalysis parameters and a slight increase in liver weight were all recorded at 400 ppm at the end of the treatment period but not after the 4-week recovery period and were considered not to be adverse. In males in all exposure groups an increased incidence and severity of intra-epithelial hyaline droplets and focal or multifocal basophilic tubules were noted in the kidneys and were considered to be consistent with alpha-2u-nephropathy and therefore of no relevance to humans (Swenberg, 1993). The No-Observed-Adverse-Effect-Concentration (NOAEC) was therefore considered to be 400 ppm, the highest concentration tested.

In an OECD 422 study (Dow Corning Corporation, 2008), Sprague-Dawley rats were exposed, whole body, to hexamethyldisilazane vapour for 6 hours/day, 7 days/week for 4 weeks at 0, 25, 100 or 400 ppm. Clinical signs, limited to uncoordinated gait and decreased activity immediately after exposure, reduced body weight gain and centrilobular hypertrophy were noted at 400 ppm. Based on these findings the NOAEC was considered to be 100 ppm (660 mg/m3).

There is also an OECD 422 inhalation study on the hydrolysis product, trimethylsilanol (WIL Research Laboratories, 2008) in which test substance-related effects were limited to changes in hematology (lower eosinophil and lymphocyte counts for males) and serum chemistry (higher alanine aminotransferase for males and toxicity phase females) at 600 ppm. These changes occurred in the absence of correlating histologic changes and were not considered adverse. Therefore an exposure level of at least 600 ppm (2214 mg/m3) was considered to be the NOAEC.

In an OECD 414 oral study on the hydrolysis product, trimethylsilanol (Harlan, 2014b) repeat-dose adminstration to pregnant female ratsresulted in clinical signs (including uncoordinated movement and/or decreased activity) and reduced food consumption and body weight gain at the highest dose tested, 450 mg/kg/day.

Hexamethyldisilazane hydrolyses very rapidly in contact with water (<0.04 minutes, <0.5 minutes and <0.1 minutes at pH 4, 7 and 9 and 1oC) generating trimethylsilanol and ammonia. Reaction rate also increases with temperature, so hydrolysis at physiologically relevant temperatures and pH 7 (relevant for conditions in the lung following inhalation administration) will be even faster. Therefore read-across from the hydrolysis product, trimethylsilanol, to hexamethyldisilazane for the supporting inhaled OECD 422 study is considered valid.

Repeat dose information (OECD SIDS, 2007) for the non-silanol hydrolysis product, ammonia, indicates that in studies conducted by the inhaled route, the main effects are irritation and inflammation of the respiratory tract. Growth retardation and effects on the CNS were also noted in inhaled studies in rats conducted with ammonium sulfate.

Although effects on the respiratory tract were not noted in the repeat dose inhalation study with hexamethydisilazane, the clinical signs and body weight effects may be attributable to its rapid hydrolysis and production of ammonia and/or trimethylsilanol.

There were no repeat dose data for hexamethyldisilazane via the oral and dermal routes.


Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Justification for classification or non-classification

Based on the available data hexamethyldisilazane does not require classification for specific target organ toxicity according to Regulation (EC) 1272/2008.