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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991
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

Constituent 1
Chemical structure
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
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 / concentrationsopen allclose all
Dose / conc.:
0 mg/m³ air
Remarks:
Control
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.

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