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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
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:
One -Generation Reproduction Study of test chemical in Rats
Author:
OECD SIDS
Year:
2008
Bibliographic source:
OECD HPV Chemical Programme, SIDS Dossier, 2008

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Guideline 422
Principles of method if other than guideline:
One -Generation Reproduction Study of test chemical in Rats
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetraethyl orthosilicate
EC Number:
201-083-8
EC Name:
Tetraethyl orthosilicate
Cas Number:
78-10-4
Molecular formula:
C8H20O4Si
IUPAC Name:
Tetraethyl silicate
Details on test material:
- IUPAC Name - Tetraethyl orthosilicate
- InChI - 1S/C8H20O4Si/c1-5-9-13(10-6-2,11-7-3)12-8-4/h5-8H2,1-4H3
- Smiles - [Si](OCC)(OCC)(OCC)OCC
- Molecular formula :C8H20O4Si
- Molecular weight :208.328 g/mole
- Substance type:Organ metallic
- Physical state:liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test chemical dissolved in corn oil.

DIET PREPARATION
- Rate of preparation of diet (frequency):
- Mixing appropriate amounts with (Type of food):
- Storage temperature of food:

VEHICLE
- Justification for use and choice of vehicle (if other than water): Test chemical dissolved in corn oil.

- Concentration in vehicle: 0,10, 50 and 100 mg/kg bw/day
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Details of mating
- M/F ratio per cage: 1:1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available

- Further matings after two unsuccessful attempts: [no / yes (explain)] No data available

- After successful mating each pregnant female was caged (how):
- Any other deviations from standard protocol: No data available

Duration of treatment / exposure:
28 days in males; up to 53 days in females
Frequency of treatment:
Daily
Duration of test:
54 days
Doses / concentrations
Remarks:
0,10, 50 and 100 mg/kg bw/day
No. of animals per sex per dose:
Total :80
0 mg/kg /day: 10males and 10 females
10 mg/kg /day: 10males and 10 females
50mg/kg /day:10males and 10 females
100 mg/kg /day:10males and 10 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data available

Examinations

Maternal examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: Body weight were recorded at designated intervals
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): food consumption were recorded at
designated intervals
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes / No / No data
- Time schedule for examinations:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes: [all per litter / half per litter / #? per litter ] / No / No data
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Induced a transient decrease in body weight gain during lactation at 100 mg/kg/day. Slight transient decrease in body weight gain was also noted in females of the toxicity group at 100 mg/kg/day but no change in body weight was noted in males of the principal group at any dose-level
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:
effects observed, treatment-related
Description (incidence and severity):
slightly lower sodium, potassium and glucose levels in males given 100 mg/kg/day,
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Tubular nephropathy was observed among some treated males (principal group) at 50 and 100 mg/kg/day and females (toxicity group) at 100 mg/kg/day. This was associated with slightly lower plasma levels of sodium, potassium and glucose. No signs of substance-induced maternal or paternal toxicity occurred at the low dose-level (10 mg/kg/day).
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
changes in pregnancy duration
clinical signs
dead fetuses
food consumption and compound intake
histopathology: non-neoplastic
mortality
number of abortions
Remarks on result:
other: There were no effects on mating performance or fertility

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
changes in sex ratio
fetal/pup body weight changes
changes in postnatal survival
external malformations
Remarks on result:
other: No effects on developmental parameters was observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 100mg/kg/day, When male and female rats were treated with test chemical orally.
Executive summary:

The combined repeated reprductive and developmental toxicity study of test chemical was performed on male and female Sprague-Dawley rats. The test chemical was dissolved in corn oil and administered via oral gavage route throughout the pre-mating period (15 days), during the mating and post-mating periods until final sacrifice for the males (at least 4 weeks in total)and throughout pre-mating (15 days) and mating period, during pregnancy and lactation, until day 4 post-partum inclusive (or until sacrifice for un-mated females) for the females. Three groups of 10 males and 10 females received the test chemical by oral gavage once a day at 10, 50 or 100 mg/kg/day while A group of 10 males and 10 females was given the vehicle (corn oil) under the same experimental conditions and acted as a control group.
 Mortality and clinical signs were checked daily in all animals. Body weight and food consumption were recorded at designated intervals. Females were paired with males from the same dose-level group until mating occurred or 2 weeks had elapsed. Gestation was monitored. Females were allowed to deliver normally and to rear their progeny until day 5 post-partum. During the lactation period, the pups were examined daily for survival, external abnormalities and clinical signs. Pup body weights were recorded on days 1 and 4 post-partum. At final sacrifice of the parents, specified organs were weighed and a complete macroscopic post-mortem examination was performed. A microscopic examination was performed on a range of sampled tissue and organs for all males of the principal groups and females of the toxicity groups; a microscopic examination was not performed on the principal group females.There were no effects on mating performance or fertility. There were no intergroup differences for litter size, sex ratio or viability. There were no effects on offspring development. There were no clinically observable signs of toxicity in offspring from treated animals.Hence No Observed Adverse Effect Level (NOAEL) for reproductive and developmental toxicity was considered to be 100mg/kg/day, When male and female rats were treated with test chemical orally.