Silicic acid, ethyl ester

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data from secondary source

Data source

Reference

Reference Type:

other: secondary source

Title:

Subacute inhalation toxicity study in rats was performed to determine the toxic nature of the test chemical

Author:

OECD SIDS

Year:

2003

Bibliographic source:

SIDS Initial Assessment Report ,2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Principles of method if other than guideline:

Subacute inhalation toxicity study in rats was performed to determine the toxic nature of the test chemical.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-aminopropyltriethoxysilane

EC Number:

213-048-4

EC Name:

3-aminopropyltriethoxysilane

Cas Number:

919-30-2

Molecular formula:

C9H23NO3Si

IUPAC Name:

3-aminopropyltriethoxysilane

Details on test material:

- IUPAC Name - 3-aminopropyltriethoxysilane
- InChI - 1S/C9H23NO3Si/c1-4-11-14(12-5-2,13-6-3)9-7-8-10/h4-10H2,1-3H3
- Smiles - [Si](CCCN)(OCC)(OCC)OCC
- Molecular formula :C9H23NO3Si
- Molecular weight :221.371 g/mole
- Substance type:Organ metallic
- Physical state:liquid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

Details on test animal
- Age at study initiation:
101 to 153 grams

Administration / exposure

Route of administration:

inhalation: aerosol

Vehicle:

air

Details on inhalation exposure:

The inhalation chambers used in the study were constructed of stainless steel with glass windows for animal observations. Chamber volume was 1330 liters and the airflow was approximately 300 L/min (13.5 air changes per hour). Chamber temperature and relative humidity were determined at least twelve times per exposure. The animals were acclimated to the chamber (air-only exposure) for 2 days prior to the initiation of the exposure regimen. The position of the cages was rotated daily within each chamber. Target concentrations of 0 and 150 mg/m3 were selected for this study. A 2% test substance hydrolysate solution was
prepared daily and used to generate the aerosol atmosphere in the inhalation chamber. Chamber concentrations of test substance hydrolysate were determined by gravimetric methods. The nominal concentration was calculated daily by dividing the total amount of material delivered to the chamber by the total airflow rate. The particle size distribution was measured once a day for the first 16 exposure days of the study. The data collected were analyzed by probit analysis (Finney, 1964) to obtain the mass median aerodynamic diameter (MMAD) and the geometric standard deviation

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 hours per day for a total of 19 exposures over 4 weeks

Frequency of treatment:

Five days/week for three weeks and four consecutive days during the fourth week

Doses / concentrations

Remarks:

0 and 147 mg/m3

No. of animals per sex per dose:

Total:30
0 mg/m3:15 male
147 mg/m3:15 male

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Clinical observations were performed daily. All animals were weighed prior to study
initiation, weekly during the study, and immediately prior
to study termination

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

Ten animals of the control and treated groups were subjected to a complete necropsy and the following tissues were fixed in 10% neutral buffered formalin for histologic evaluation: gross lesions, larynx, lungs, trachea, nasal turbinates and kidneys. For the satellite groups, the larynges of three control animals and five test substance-treated animals were taken and immersion-fixed in 2% glutaraldehyde for possible electron microscopic examination. The remaining two rats from thecontrol group were subjected to a complete necropsy and perfusion-fixed with 5% methanol-free EM grade fomaldehyde. The larynges from these two rats were then further immersion-fixed in 2% glutaraldehyde. Other organs (brain, spinal cord, and peripheral nerves) were taken from these control animals and processed for light microscopic evaluation.

Statistics:

The data for continuous, parametric variables were intercompared for the exposure and control groups by use of Levene's test for homogeneity of variances and by t-tests. If Levene's test indicated homogeneous variances, the groups were compared by pooled variance t-tests. If Levene's test indicated heterogeneous
variances, the groups were compared by separate variance t-test. Frequency data were compared using Fisher's exact tests. All statistical tests, except the frequency comparisons, were performed using BMDP Statistical Software (Dixon, 1985). The frequency data tests are described in Biometry (Sokal and Rohlf, 1969). The probability value of p < 0.05 (two-tailed) was used as the critical level of significance for all tests.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

No exposure-related clinical signs were observed during the study.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A depression in body weight gain was observed for the test substance-exposed animals during the first week of the study.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Description (incidence and severity):

At necropsy, focal/multifocal color changes of the lungs were noted in ninety percent of the animals of the test substance-exposed group.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Histological examination showed nonspecific irritant, inflammatory, and metaplastic changes within the respiratory tracts of test substance-exposed rats.
Laryngeal lesions included squamous metaplasia and foci of minimal granulomatous laryngitis. Other microscopic changes included the presence of cytoplasmic hyalinization (mild to moderate) within the olfactory mucosa, squamous metaplasia (minimal to mild) within the nasal mucosa, cellular hyperplasia within the trachea, alveolar histiocytosis, bronchopneumonia, interstitial pneumonitis and alveolar type II pneumocyte hyperplasia within the lungs

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEC

Effect level:

147 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

gross pathology

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

Remarks on result:

other: No toxic effects were observed

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Applicant's summary and conclusion

Conclusions:

The No observed Adverse Effect concentration (NOAEC) for the test chemical using male rats was considered to be 147mg/m3

Executive summary:

The subacute inhalation toxicity study of test chemical was performed in maleFischer 344 rats . Target concentrations of 0 and 150 mg/m3 were selected for this study. A 2% test substance hydrolysate solution was prepared daily and used to generate the aerosol atmosphere in the inhalation chamber. Chamber concentrations of test substance hydrolysate were determined by gravimetric methods. The nominal concentration was calculated daily by dividing the total amount of material delivered to the chamber by the total airflow rate. 15 rats per group were exposed to test chemical 6 hours per day for a total of 19 exposures over 4 weeks. Clinical observations were performed daily. All animals were weighed prior to study initiation, weekly during the study, and immediately prior to study termination. Ten animals of the control and treated groups were subjected to a complete necropsy and the following tissues were fixed in 10% neutral buffered formalin for histologic evaluation: gross lesions, larynx, lungs, trachea, nasal turbinates and kidneys. For the satellite groups, the larynges of three control animals and five test substance-treated animals were taken and immersion-fixed in 2% glutaraldehyde for possible electronmicroscopic examination. The remaining two rats from the control group were subjected to a complete necropsy and perfusion-fixed with 5% methanol-free EM grade fomaldehyde. The larynges from these two rats were then further immersion-fixed in 2% glutaraldehyde. Other organs (brain, spinal cord, and peripheral nerves) were taken from these control animals and processed for light microscopic evaluation. No exposure-related clinical signs and mortality were observed during the study. A depression in body weight gain was observed for the test substance-exposed animals during the first week of the study. At necropsy, focal/multifocal color changes of the lungs were noted in ninety percent of the animals of the test substance-exposed group. Histological examination showed nonspecific irritant, inflammatory, and metaplastic changes within the respiratory tracts of test substance-exposed rats. Laryngeal lesions included squamous metaplasia and foci of minimal granulomatous laryngitis. Other microscopic changes included the presence of cytoplasmic hyalinization (mild to moderate) within the olfactory mucosa, squamous metaplasia (minimal to mild) within the nasal mucosa, cellular hyperplasia within the trachea, alveolar histiocytosis, bronchopneumonia, interstitial pneumonitis and alveolar type II pneumocyte hyperplasia within the lungs. HenceThe No observed Adverse Effect concentration (NOAEC) for the test chemical using male rats was considered to be 147mg/m3