[No public or meaningful name is available]

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

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.

 

Repeated dose toxicity: inhalation

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

 

Repeated dose toxicity: dermal

The acute dermal toxicity value for the test substance (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

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

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

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:

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

Dose / conc.:

70 mg/kg bw/day (nominal)

Dose / conc.:

200 mg/kg bw/day (nominal)

Dose / conc.:

600 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes, concurrent vehicle

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.

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

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

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

Critical effects observed:

no

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from secondary source

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation, other

Data waiving:

exposure considerations

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: dermal, other

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Additional information

Repeated dose toxicity: Oral

Study 1: 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.

 

Study 2: The test substance was tested for the repeated dose toxicity via oral route in rats. 10 rats per sex per dose of Sprague-Dawley strain were treated with the test substance. Rats were treated at the dose concentraion 0, 25, 125,  and 500 mg/kg bw/day. No treatment related adverse effects were observed at the highest dose of 500 mg/kg bw/day. Hence, the No Observed Adverse Effect Level (NOAEL) can be considered to be greater than 500 mg/kg bw/day.

 

Repeated dose toxicity: inhalation

a short-term toxicity study does not need to be conducted because exposure of humans via inhalation in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

 

Repeated dose toxicity: dermal

The acute dermal toxicity value for the test substance (as provided in section 7.2.3) is >2000 mg/kg body weight. Considering this, the end point for repeated dermal toxicity is considered as waiver.

Justification for classification or non-classification

Based on the data available for the target chemical, the test chemical does not show repeated dose toxicity by oral route of exposure. Hence the test chemical is not likely to be toxic upon repeated exposure by oral route, dermal and inhalation route of exposure.