Silicic acid, ethyl ester

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / 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:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

One -Generation Reproduction Study of test chemical in Rats

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

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 species / strain selection:

No data available

Sex:

male/female

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

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

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days in males; up to 53 days in females

Frequency of treatment:

daily

Details on study schedule:

No data available

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

Positive control:

No data available

Examinations

Parental animals: Observations and 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

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

the pups were examined daily for survival, external abnormalities and clinical signs. Pup body weights were recorded on days 1 and 4 post-partum

Postmortem examinations (parental animals):

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.

Postmortem examinations (offspring):

No data available

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

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:

no effects observed

Haematological findings:

no effects observed

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 and 50mg/kg/day dose group.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

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

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Description (incidence and severity):

There were no effects on mating performance or fertility

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

clinical biochemistry

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

reproductive performance

Remarks on result:

other: There were no effects on mating performance or fertility

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

not specified

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:

not specified

Urinalysis findings:

not specified

Sexual maturation:

not specified

Anogenital distance (AGD):

not specified

Nipple retention in male pups:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Other effects:

no effects observed

Description (incidence and severity):

There were no intergroup differences for litter size, sex ratio or viability. There were no effects on offspring development

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not specified

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

100 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

clinical signs

mortality

gross pathology

other: There were no intergroup differences for litter size, sex ratio or viability. There were no effects on offspring development

Remarks on result:

other: There were no intergroup differences for litter size, sex ratio or viability. There were no effects on offspring development

Target system / organ toxicity (F1)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Overall reproductive toxicity

Reproductive 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.