Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 640 mg/m³
Study duration:
subacute
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information
In an OECD 422 study (Dow Corning Corporation, 2008) conducted by the inhaled route, there was no effect of hexamethyldisilazane on the sexual function and fertility of Sprague-Dawley rats up to 400 ppm (2640 mg/m3), the highest concentration tested. There is also an OECD 422 inhalation study on the hydrolysis product, trimethylsilanol (WIL Research Laboratories, 2008) in which no effects on the sexual function and fertility of Sprague-Dawley rats were noted up to 600 ppm (2214 mg/m3) the highest concentration tested. 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. No effects on sexual function and fertility have been noted for the non-silanol hydrolysis product, ammonia (OECD SIDS, 2007).

Short description of key information:
There were no effects on reproductive function noted in inhaled OECD 422 studies with hexamethyldisilazane (Dow Corning Corporation, 2008) or the hydrolysis product trimethylsilanol (WIL Research Laboratories, 2008) up to the maximum concentrations tested, 400 ppm (2640 mg/m3) or 600 ppm (2214 mg/m3) respectively.

Justification for selection of Effect on fertility via inhalation route:
Study was conducted in accordance with an appropriate guideline and in compliance with GLP.

Effects on developmental toxicity

Description of key information
In an oral OECD 414 developmental toxicity study with the hydrolysis product, trimethylsilanol (Harlan, 2014), the maternal and fetal NOAELs were 150 mg/kg/day. There were no effects on developmental paramters noted in inhaled OECD 422 studies with hexamethyldisilazane (Dow Corning Corporation, 2008) and only slight delays in development and only variations with high spontaneous frequency were observed for the hydrolysis product trimethylsilanol (WIL Research Laboratories, 2008) up to the maximum concentrations tested, 400 ppm (2640 mg/m3) or 600 ppm (2214 mg/m3) respectively
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
150 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 640 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information
In the key OECD 414 developmental toxicity study (Harlan, 2014) oral administration of the hydrolysis product, trimethylsilanol, to rats resulted 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. The reductions in food consumption and body weight again were considered to be adverse so the maternal No-Observed-Adverse-Effect-Level was considered to be 150 mg/kg/day. Reduced fetal weight, delayed ossification and increased incidence of some cartilaginous variations were noted in fetuses at 450 mg/kg/day and considered to be adverse, therefore the fetal NOAEL was considered to be 150 mg/kg/day. In an OECD 422 study (Dow Corning Corporation, 2008) conducted by the inhaled route, there was no effect of the registered substance, hexamethyldisilazane, on developmental parameters of Sprague-Dawley rats up to 400 ppm (2640 mg/m3), the highest concentration tested. In an OECD 422 inhalation study on the hydrolysis product, trimethylsilanol (WIL Research Laboratories, 2008) no effects on developmental parameters of Sprague-Dawley rats were noted up to 600 ppm (2214 mg/m3) the highest concentration tested. 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. As the hydrolysis reaction may be acid or based catalysed and can be assumed to be first order, the rate of reaction is expected to be slowest at pH 7 and increase as the pH is raised or lowered. Reaction rate also increases with temperature, so hydrolysis at physiologically relevant temperatures and pH 2 (relevant for conditions in the stomach following oral administration) or 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 key oral developmental toxicity study and supporting inhaled study is considered valid. No effects on developmental parameters have been noted for the non-silanol hydrolysis product, ammonia (OECD SIDS, 2007).

Justification for selection of Effect on developmental toxicity: via oral route:
Study was conducted according to an appropriate guideline and in compliance with GLP.

Justification for selection of Effect on developmental toxicity: via inhalation route:
Study was conducted in accordance with an appropriate guideline and in compliance with GLP.

Justification for classification or non-classification

Based on the available data hexamethyldisilazane does not require classification for reproductive or developmental toxicity according to Regulation (EC) 1272/2008.