Hydroxytrimethylsilane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

In an inhalation Combined Repeated Dose Toxicity Study with Reproductive/Developmental Toxicity Screening Test (WIL, 2008) conducted to OECD Test Guideline 422 and in compliance with GLP, there were no adverse effects on maternal animals and no adverse effects on reproduction parameters. Therefore, under the conditions of this screening study, an exposure level of ≥600 ppm (≥2249.82 mg/m3) trimethylsilanol was considered to be the NOAEL for parental general toxicity and reproductive toxicity.

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

2 249.82 mg/m³

Study duration:

subacute

Species:

rat

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In an inhalation Combined Repeated Dose Toxicity Study with Reproductive/Developmental Toxicity Screening Test (WIL, 2008) conducted to OECD Test Guideline 422 and in compliance with GLP, three groups of Sprague-Dawley rats, were exposed via whole-body inhalation to vapour atmospheres of trimethylsilanol, 6 hours/day, 7 days/week. Target exposure concentrations were 60, 300 and 600 parts per million (ppm). Treatment-related effects were limited to changes in haematology (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. Mean mating, fertility and copulation/conception indices for all exposure concentrations were similar to the control group.  Mean gestation lengths, postnatal survival and F₁ body weights were similar to the control group.  Therefore, under the conditions of this screening study, an exposure level of 600 ppm (≥2249.82 mg/m³) trimethylsilanol was considered to be the NOAEL for parental general toxicity and reproductive toxicity. Trimethylsilanol has also been tested in a valid uterotrophic assay, conducted according to OECD TG 440 (draft), and in compliance with GLP, for ability to induce estrogenic or antiestrogenic effects in female rats (Dow Corning Corporation, 2008). Exposure of rats to 600 ppm of test substance for 6 hours per day for 3 consecutive days did not induce any changes in uterine weight or any estrogenic or anti-estrogenic response. Positive and negative controls were also included and gave the expected results.

Effects on developmental toxicity

Description of key information

In an oral prenatal developmental toxicity study (Harlan, 2014) conducted to OECD 414 and in compliance with GLP, administration of trimethylsilanol by oral gavage to Sprague-Dawley rats from Day 6 to 20 of pregnancy at 0, 50, 150 or 450 mg/kg/day resulted in a NOAEL for maternal and developmental toxicity of 150 mg/kg bw/day.

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

Quality of whole database:

The key study was conducted according to OECD Test Guideline 414 and in compliance with GLP.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

2 249.82 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The inhalation study was conducted to OECD test guideline 422 and in compliance with GLP.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

In an oral prenatal developmental study (Harlan, 2014) conducted to OECD 414 and in compliance with GLP, administration of trimethylsilanol by oral gavage to Sprague-Dawley rats from Day 6 to 20 of pregnancy at doses of 0, 50, 150 or 450 mg/kg/day resulted in maternal toxicity (reduced corrected body weight gains) at 450 mg/kg bw/day.

Reduced fetal weight, delayed ossification and increased incidence of some cartilaginous variations were noted in fetuses at 450 mg/kg/day. The slight delay in ossification at the LOAEL of 450 mg/kg bw/day correlates with the lower fetal body weight which again correlates with the decrease in food consumption, and in mean absolute body weight and body weight gain of the parental animals. Thus, the findings are a secondary effect in response to the treatment related maternal effects observed at this dose level.

The increased incidence of supernumerary rudimentary ribs, long ventral plate and long or interrupted costal cartilage at 450 mg/kg are reported as variations with high spontaneous incidence in this strain and therefore neither adverse nor an indication for a biologically relevant disturbance of the fetal development. Therefore, the findings at 450 mg/kg do not trigger classification for developmental toxicity and the NOAEL for maternal and developmental toxicity was considered to be 150 mg/kg bw/day.

No adverse effects on developmental parameters were observed in an inhalation Combined Repeated Dose Toxicity Study with Reproductive/Developmental Toxicity Screening Test (WIL, 2008) conducted to OECD test guideline 422 and in compliance with GLP. The NOAEC for trimethylsilanol in this study was ≥600ppm (2249.82 mg/m³).

Justification for classification or non-classification

Based on the available studies there is no requirement for the classification of trimethylsilanol for adverse effects on reproduction or development according to Regulation (EC) No 1272/2008.