Hydroxytrimethylsilane

Endpoint summary

Description of key information

In an inhalation OECD Test Guideline 422 screening study (WIL Research Laboratories, 2008), which was conducted to GLP, the NOAEC for trimethylsilanol was ≥600 ppm (2213.5 mg/m3).

In a 28-day oral repeated dose toxicity study (Bayer AG, 1986) conducted to OECD Test Guideline 407 and in compliance with GLP, the NOAEL for trimethylsilanol was 250 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

There is only one oral repeated dose study available for which adequate study details are available for review. It was conducted according to OECD Test Guideline 407 and in compliance with GLP.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

2 213.5 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study was conducted according to OECD Test Guideline 422 and in compliance with GLP. It was selected as the key study as it was conducted over the longest duration of exposure.

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

2 213.5 mg/m³

Study duration:

subacute

Species:

rat

Quality of whole database:

The key study was conducted according to OECD Test Guideline 422 and in compliance with GLP.

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 an inhalation OECD Test Guideline 422 screening study (WIL Research Laboratories, 2008), which was conducted to GLP, trimethylsilanol-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 to be adverse. Therefore, under the conditions of this screening study, an exposure level of 600 ppm (2213.5 mg/m³) was considered to be the NOAEC for trimethylsilanol. The NOAEC from this study was selected as the most appropriate starting point for the inhalation DNELs.

In a good quality 2-week dose range-finding study (WIL Research Laboratories, 2007), trimethylsilanol-related effects were limited to the 600 ppm exposure level and consisted of CNS/behaviour-related clinical signs of hypoactivity (males) and impaired equilibrium (females) and macroscopic findings of diffusely pale lungs. The NOAEL for trimethylsilanol administered to Sprague-Dawley rats by inhalation for 2 consecutive weeks was 300 ppm.

In an oral gavage study apparently conducted to OECD Test Guideline 407, groups of Wistar rats (5/sex/dose) were given daily doses of either 0 (castor oil vehicle only), 80, 250 and 750 mg/kg bw/day trimethylsilanol for 28 days. Clinical observations, food and water intake, body weights, organ weights, clinical chemistry, haematology, and histopathology were all recorded. Toxicologically relevant adverse effects (reduced body weight gain, reduced alkaline phosphatase, reduced glucose (males), increased liver weights (females), and increased adrenal weights (males), and minor deposits in the bile ducts) were observed at the highest dose of 750 mg/kg bw/day. The NOAEL was 250 mg/kg bw/day, as effects observed at this or the lower dose of 80 mg/kg bw/day, were not dose-dependent and often values were within the normal range for historical controls. The NOAEL from this study was selected as the starting point for dermal DNELs as it represents the most conservative starting point in the absence of dermal data.

Based on an oral 28 day repeated dose toxicity study conducted using a protocol similar to OECD 407 and in compliance with GLP the NOAEL for trimethylsilanol was 160 mg/kg bw/day based on clinical signs of toxicity (narcosis), decreased body weight gain, haematological effects, and/or organ weight effects (study report currently not available - results taken from Japanese language website).

Justification for classification or non-classification

Based on the available oral and inhalation studies, trimethylsilanol does not require classification for specific organ toxicity following repeated administration according to Regulation (EC) No. 1272/2008.