3-aminopropyltriethoxysilane

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1989-08-14 to 1989-09-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes

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:

silane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Fischer 344

Remarks:

/CDF

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, NY)
- Females nulliparous and non-pregnant: n/a
- Age at study initiation: 20 days
- Weight at study initiation:
- Fasting period before study:
- Housing: 1-2 rats per cage in stainless steel, wire-mesh cages, 23.5 cm * 20cm * 18 cm.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not specified

DETAILS OF FOOD AND WATER QUALITY: Water was provided by an automatic watering system (Municipal Authority of Westmoreland County, Greensburg, PA)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not specified
- Humidity (%): not specified
- Air changes (per hr): 13.5
- Photoperiod (hrs dark / hrs light): 12/12 hours.

IN-LIFE DATES: From: 24th of July 1989 to 29th of September 1989 for the control group and from the 18th of July 1989 to 29th of September 1989 for the exposure group.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: water

Mass median aerodynamic diameter (MMAD):

2.92 µm

Geometric standard deviation (GSD):

1.74

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The chambers were of stainless steel with glass windows for animal observations. The chamber volume was 1330 litres.
- Method of holding animals in test chamber: not specified
- Source and rate of air: the airflow was approximately 300 L/min (13.5 air changes per hour).
- Method of conditioning air: not specified
- System of generating particulates/aerosols: A Dwyer Magnehelic pressure gauge
- Temperature, humidity, pressure in air chamber: 18-22°C (64-71°F) with a relative humidity of 46-66 % for the exposed animals and 17-21°C (62-70°F) with a relative humidity of 45-77 % for the animals in the control group.
- Air flow rate: 300 L/min
- Air change rate: 13.5 air changes per hour
- Method of particle size determination: TSI Aerodynamics particle Sizer and a 20:1 diluter.
- Treatment of exhaust air:

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: not specified

Analytical verification of doses or concentrations:

yes

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

Doses / concentrations 1

Dose / conc.:

0 mg/m³ air

Remarks:

Control

Doses / concentrations 2

Dose / conc.:

147 mg/L air (analytical)

Remarks:

Test group

No. of animals per sex per dose:

15 males for the test and control group respectively

Control animals:

other: concurrent; filtered air

Details on study design:

Post-exposure period: Not applicable. The rats were observed daily during exposure and observations were recorded on a group basis. Preceding and following each exposure and on weekends, observations were recorded for animals exhibiting overt clinical signs.

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily when not exposed. When exposed, observations were recorded on a group basis.
- Cage side observations checked in table were included: no

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily when not exposed. When exposed, observations were recorded on a group basis.

BODY WEIGHT: Yes
- Time schedule for examinations: weekly including prior to to initiation of the treatment and immediately preceding sacrifice.

FOOD CONSUMPTION AND COMPOUND INTAKE: n/a

FOOD EFFICIENCY: n/a

WATER CONSUMPTION AND COMPOUND INTAKE: No

OPHTHALMOSCOPIC EXAMINATION: Not specified

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No

OTHER: Necropsy and histopathology evaluations occurred in all animals being exposed and includes the following tissues: gross lesions, larynx, lungs, trachea, nasal turbinates and kidneys.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

The data for continuous and 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. 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

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

A significantly lower body weight gain was observed in the exposed animals between the initiation week until week 3. This was considered as not treatment related since the body weights were different prior to the start of the exposure regimen. The difference in preexposure body weight was a result of randomising the animals at different times since they were received at different times. However, body weight gain for the exposure group was statistically lower than the control group during the first week of the study which was considered as treatment related. Body weight gain was comparable or greater than the control group after the first week of exposure. Specifically, body weight gain was statistically significant greater in the exposure group at the end of the 4-week exposure period.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not specified

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not specified

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Cytoplasmic hyalinisation (mild to moderate) was observed within the olfactory mucosa of the nasal cavity and was characterised by the presence of smooth homogenous oesinophilic material within the cytoplasm. Two of the rats with laryngeal squamous metaplasia had also minimal degrees of granulomatous laryngitis. Moreover, alveolar histiocytosis, bronchopneumonia and interstitial pneumonitis were observed within the lungs.

Histopathological findings: neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Foci of squamous metaplasia (minimal to mild) were present within the larynx and nasal mucosa of exposed rats. The squamous metaplasia observed in the larynx was observed in the region of the transitional epithelium which is susceptible to toxic injury. Cellular hyperplasia was observed within the trachea of exposed animals. Within the lungs, alveolar type II pneumocyte hyperplasia was observed.

Other effects:

effects observed, non-treatment-related

Description (incidence and severity):

The slightly higher mineralisation of the corneal epithelium and at the corneoscleral junction was not considered to be exposure related since these formations are common in Fischer 344 rat strain and the intergroup frequency of these lesions can vary widely.

Effect levels

Dose descriptor:

LOAEC

Effect level:

>= 147 mg/L air (analytical)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In a 28-day repeated inhalation study, which was conducted according to a protocol similar to OECD TG 414 and in compliance with GLP, it was reported that exposure to an aerosol of the test substance hydrolysate (147 mg/L) was associated with laryngeal changes, however, not laryngeal granulomas.