Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(isopropenyloxy)vinylsilane
EC Number:
239-362-1
EC Name:
Tris(isopropenyloxy)vinylsilane
Cas Number:
15332-99-7
Molecular formula:
C11H18O3Si
IUPAC Name:
ethenyltris(prop-1-en-2-yloxy)silane
Constituent 2
Reference substance name:
Tris(isopropenyloxy)(vinyl)silane
IUPAC Name:
Tris(isopropenyloxy)(vinyl)silane
Test material form:
other: liquid
Details on test material:
- Substance type: monoconstituent
- Physical state: liquid
- Analytical purity: >99.5%
- Impurities (identity and concentrations):
- Purity test date:
- Lot/batch No.: 012
- Expiration date of the lot/batch: no information
- Stability under tes conditions: stable under storage conditions, hydrolyses in presence of moisture at room temperature.
- Storage condition of test material: In original container, at room temperature, protected from light.
- Other: Gloves, goggles and full face respirator were sufficient to assure personnel health.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: KFM Kleintierfarm, Madoering AG, CH-4414-Fuellinsdorf, Switzerland
- Age at study initiation: males: 8 weeks, females: 10 weeks
- Weight at study initiation: males 180-200 grams, females 181-199 grams
- Fasting period before study: no
- Housing: groups of 5 in Macrolon type-4 cages; softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Remarks on MMAD:
MMAD / GSD: No data
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: according to method of Sachsse et al (1973; 1976)
- Method of holding animals in test chamber: the animals were confined separately in Macrolon tubes positioned radially around exposure chamber.
- Source and rate of air: no details
- Method of conditioning air: no details
- System of generating particulates/aerosols: for low concentration, the exposure atmosphere was generated by bubbling air through the test article in a fritted flask. For medium and high concentrations, the test article was place in a syringe connected to a pump feeding a nebuliser. The test atmosphere generated by the nebuliser was diluted with clean and dry air to achieve the concentrations required.
- Temperature, humidity, pressure in air chamber: these were monitored but data not presented in report
- Air flow rate: no data
- Air change rate: no data
- Method of particle size determination: no data
- Treatment of exhaust air: no data

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
6 hours per day
Frequency of treatment:
5 days per week for 93 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 0.0249, 0.289 and 2.025 mg/l air
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0, 0.0078, 0.081 and 1.105 mg/l air
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
0, 7.8, 81 and 1105 mg/m³ air
Basis:
other: conversion analytical concentration from mg/l to mg/m³
No. of animals per sex per dose:
15
Control animals:
yes, sham-exposed

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
no mortalities, slight body weight loss, paresis, abdominal skin swelling and alopecia observed in females of mid and high dose groups from week 11
Mortality:
mortality observed, treatment-related
Description (incidence):
no mortalities, slight body weight loss, paresis, abdominal skin swelling and alopecia observed in females of mid and high dose groups from week 11
Body weight and weight changes:
no effects observed
Description (incidence and severity):
the slight body weight loss in mid and high dose females from week 11 was not considered significant
Food consumption and compound intake (if feeding study):
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
however, lungs/body weight ratios were significantly increased in high dose group males
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
histopathology alveolar macrophage aggregations and associated chronic interstitial pneumonia and alveolar epithelialisation in high dose group
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEC
Effect level:
> 81 - < 1 105 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects histopathology: alveolar macrophage aggregations and associated chronic interstitial pneumonia and alveolar epithelialisation observed in high dose group

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The exposure of rats to tris(isopropenyloxy)(vinyl)silane for 6 hours per day, 5 days per week for 93 days at analytical concentrations of 0, 7.8, 81 and 1105 mg/m³ resulted in no mortalities, and minimal clinical effects in females of the mid and high dose groups from week 11. The study was conducted according to OECD 413 (1981) and in compliance with GLP. On necroscopy, histopathological examination revealed alveolar macrophage aggregations and associated chronic interstitial pneumonia and alveolar epithelialisation in the high dose group. These findings are consistent with lung lipidosis. It was concluded by the study authors that the NOAEC was between 81 and 1105 mg/m³ air. The significance of the reported histopathological findings at the highest test concentration 1105 mg/m³ is uncertain, however these effects were not observed at concentration levels which would lead to classification for Specific Target Organ Toxicity following repeated exposure according to Regulation (EC) No 1272/2008 therefore no classification is proposed.