[No public or meaningful name is available]

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Remarks:

Read across data

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source

Data source

Reference

Reference Type:

other: Secondary source

Title:

SIDS Initial Assessment Report For SIAM 17

Author:

OECD SIDS

Year:

2003

Bibliographic source:

OECD SIDS SIAM,2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Version / remarks:

September 1998

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

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Epona Associates, LLC
- Females (if applicable) nulliparous and non-pregnant: [yes/no] : no data available
- Age at study initiation: 7 week
- Weight at study initiation: males ; 213 - 279 , females : 150 - 207
- Fasting period before study: no data available
- Housing: no data available
- Diet (e.g. ad libitum): no data available
- Water (e.g. ad libitum): no data available
- Acclimation period: no data available

DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data available
- Humidity (%): no data available
- Air changes (per hr): no data avaialble
- Photoperiod (hrs dark / hrs light): no data available

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

The test article in the vehicle, peanut oil, was administered orally by gavage to three groups of rats (five/sex) for 14 consecutive days at dosage levels of 70, 200 and 600 mg/kg bw/day. A concurrent control group received the vehicle on a comparable regimen. All animals were dosed at a volume of 10 mL/kg bw.

Details on analytical verification of doses or concentrations:

70, 200 and 600 mg/kg/day

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

70 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

600 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes / No / Not specified : yes
- Time schedule: twice daily
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / Not specified : Yes
- Time schedule: Weekly

BODY WEIGHT: Yes / No / Not specified : Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / Not specified : no data avaiable
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified : no data avaiable

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / Not specified : no data avaiable

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / Not specified : no data available
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes / No / Not specified : NO
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes / No / Not specified : NO
- Time schedule for collection of blood:
- Anaesthetic used for blood collection: Yes (identity) / No / Not specified
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

CLINICAL CHEMISTRY: Yes / No / Not specified
- Time schedule for collection of blood:
- Animals fasted: Yes / No / Not specified
- How many animals:
- Parameters checked in table [No.?] were examined.

PLASMA/SERUM HORMONES/LIPIDS: Yes / No / Not specified
- Time of blood sample collection:
- Animals fasted: Yes / No / Not specified
- How many animals:

URINALYSIS: Yes / No / Not specified
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / Not specified
- Animals fasted: Yes / No / Not specified
- Parameters checked in table [No.?] were examined.

NEUROBEHAVIOURAL EXAMINATION: Yes / No / Not specified
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

IMMUNOLOGY: Yes / No / Not specified
- Time schedule for examinations:
- How many animals:
- Dose groups that were examined:
- Parameters checked in table [No.?] were examined.

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

All analyses were conducted using two-tailed tests for minimum significance levels of 1% and 5% comparing the test article-treated groups to the control group by sex. All means were presented with standard deviations (S.D.) and the number of sampling units (N) used to calculate the means. Statistical analyses were not conducted if the number of animals was two or less. All statistical tests were performed by a Digital® MicroVAX® 3400 computer with appropriate programming. Body weight, body weight change, food consumption, clinical pathology, and absolute and relative organ weight data were subjected to a one-way analysis of variance (ANOVA), followed by Dunnett's test.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

The only definite test article-related clinical observations were signs of abnormal respiration (rales and/or labored respiration) in the 600 mg/kg bw/day group. These findings were noted in two males and two females during the last three days of dosing and/or prior to necropsy. Another female in the 600 mg/kg bw/day group had rales on one occasion during this period.

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Description (incidence and severity):

At 600 mg/kg bw/day, males had a reduction in the body weight, however, it was not a statistically significant difference.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

At 600 mg/kg bw/day, males had a reduction in the food consumption, however, it was not a statistically significant difference.

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Endocrine findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

600 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

2

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

A 2-week range-finding rat oral study found some evidence of toxicity at 600 mg/kg bw/day but no clear effects at 200 mg/kg bw/day. Dose levels of 70, 200 and 600 mg/kg bw/day were selected for the 90-day oral toxicity study.

Executive summary:

A repeated dose 90 days toxicity study of 3-aminopropyltriethoxysilane (CAS no: 919-30-2 ) was performed in rats with strain Crl:CD(SD)BR. The test substance was administered orally  in peanut oil at dosage levels  for 70, 200 and 600 mg/kg/day for 90 day. In the key 90-day oral repeated dose toxicity study, the high dose of 600 mg/kg bw/day was not well tolerated by a number of animals which were terminated prior to the scheduled necropsy. The main findings at this dose were clinical signs (rales and poor clinical condition), changes in some liver enzyme values, and/or an increase in mean relative liver weights (males only) and microscopic changes of hepatocellular vacuolation in the liver (males only). Based on these findings the NOAEL was defined as the intermediate dose of 200 mg/kg bw/day. The study was conducted according to OECD Test Guideline 408 and in compliance with GLP. In a supporting 14-day oral range-finding study conducted at the same doses that preceded the 90-day study, similar clinical signs and hepatic changes were recorded.