Registration Dossier

Administrative data

Description of key information

There are no repeated dose toxicity data on tripotassium propylsilanetriolate and testing is not technically feasible due to the corrosive nature of the test substance, so good quality data for the surrogate substance trimethoxy(methyl)silane (CAS 1185-55-3) have been used to assess the systemic toxicity of tripotassium propylsilanetriolate.

The key studies for this endpoint are an oral OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) study and an inhalation OECD Guideline 413 (90-day sub chronic study with 28-day recovery period) study. The studies were conducted according to an appropriate OECD test guideline, and in compliance with GLP (reliability score 1).

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
50 mg/kg bw/day
Study duration:
subacute
Species:
rat
System:
other: gastrointestinal and cardiovascular
Organ:
liver
thymus

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
557 mg/m³
Study duration:
subchronic
Species:
rat
System:
urinary
Organ:
bladder
kidney

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

There are no repeated dose toxicity data on tripotassium propylsilanetriolate, and testing is not technically feasible due to the corrosive nature of the test substance, so good quality data for the surrogate substance trimethoxy(methyl)silane (CAS 1185-55-3) have been used to assess the systemic toxicity of tripotassium propylsilanetriolate. A Test Plan for alkyl trialkoxysilanes is attached in Section 13. The read-across strategy for tripotassium propylsilanetriolate will be reviewed when test results are available, particular in respect of trimethoxy(propyl)silane (CAS 1067-25-0). The current approach is presented to enable interim risk characterisation.

Refer to Section 5.6.3 of the Chemical Safety Report for further details on read-across justification.

The key studies for this endpoint are an oral OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) study (DCC, 2005) and an inhalation OECD Guideline 413 (90-day sub chronic study with 28-day recovery period) study (DCC, 2008a). The studies were conducted according to an appropriate OECD test guideline, and in compliance with GLP (reliability score 1).

Oral administration of read-across substance trimethoxy(methyl)silane to male and female Sprague-Dawley rats at doses of 50, 250 or 1000 mg/kg/day for 28-29 consecutive days was generally well tolerated. Reductions in body weight and food consumption were minimal and apparent only for males in the 1000 mg/kg/day dose group. Clinical observations were limited to transient expression of a period of inactivity and/or salivation occurring directly after dosing.

Increased liver weight was observed in both sexes at dose levels of 250 and 1000 mg/kg/day. Centrilobular hepatocellular hyperplasia/hypertrophy and periportal vacuolation accompanied the increased organ weight in females and diffuse hepatocellular hypertrophy in the 1000 mg/kg/day males. Thyroid gland follicular cell hyperplasia/hypertrophy was recorded in males and females at 250 and 1000 mg/kg/day. A variety of changes in the adrenal glands of females were identified. These included hyperplasia/hypertrophy, apoptosis and lymphocytic infiltration of the zona reticularis. The effects were most prominent in the 1000 mg/kg/day dose group. Males were not similarly affected. Mucosal lipidosis of the duodenum and jejunum was recorded mainly at 1000 mg/kg/day. Thymus weight was significantly decreased for males at the 250 and 1000 mg/kg/day dose levels. This effect was not apparent in treated females.

Treatment-related effects in clinical pathology parameters were most prominent at the 250 and 1000 mg/kg/day dose levels and included acanthocytosis, elevated blood platelet concentration, prolonged prothrombin times increases in serum alanine aminotransferase activity, total protein and cholesterol and decreased serum aspartate aminotransferase and alkaline phosphatase activities.

The No-observed-adverse-effect-level (NOAEL) was considered to be 50 mg/kg/day.

Whole body inhaled administration of read-across substance trimethoxy(methyl)silane to male and female Sprague-Dawley rats at exposure concentrations of 25, 100, 400 or 1600 ppm, 5 days a week for 90 days, followed by a 28-day recovery period resulted in mortality of one 400 ppm and one 1600 ppm male.

 

Test article-relate clinical signs were limited to the 400 ppm and 1600 ppm exposure groups and included increased incidence of soiling around urogenital and abdominal regions. Body weights for the 400 ppm females and animals at 1600 ppm were generally lower than controls over the entire study.

 

Test article-related observations following inhalation exposure were primarily attributable to effects on the urinary tract. At 1600 ppm, test article exposure often led to formation of macroscopically observed urinary calculi. These could be observed macroscopically as large single or small granular calculi in the urinary bladder. Microscopically, these calculi were observed at the centre of foci of granulomatous inflammation in the renal pelvis, as fragments of crystalline material in the urinary bladder, or incorporated into the proteinacious calculi (plugs) common in male rats. In most 1600 ppm animals and a few 400 ppm animals there was some degree of diffuse urinary bladder epithelial hyperplasia as well as urinary calculi which persisted through the recovery period.

 

Based on the clinical signs along with, urinary bladder calculi and kidney findings at the 400 ppm exposure level, the No-Observed-Adverse-Effect-Concentration (NOAEC) was considered to be 100 ppm (557 mg/m3).

 


Justification for classification or non-classification

Based on the available read-across data tripotassium propylsilanetriolate is not classified for adverse effects following repeated exposures according to Regulation (EC) No 1272/2008.