Silicic acid, ethyl ester

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test

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:

Subchronic toxicity study of test chemical was performed 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:

Subchronic toxicity study of test chemical was performed in rats

GLP compliance:

not specified

Limit test:

no

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

Details on route of administration:

No data available

Vehicle:

corn oil

Details on oral 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

Duration of treatment / exposure:

28 days in males; up to 53 days in females

Frequency of treatment:

Daily

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

Observations and examinations performed and frequency:

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:

OTHER:
Detailed clinical observations and
neurobehavioral tests were conducted at designated intervals to assess behavior, main functions and reflexes (landing foot splay, rectal temperature and forelimb grip strength) and to measure motor activity over a 1- and 10-minute periods. Blood samples were collected from all males of the
principal groups and from all females of the toxicity groups at the end of the treatment period.

Sacrifice and pathology:

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.

Statistics:

No data available

Results and discussion

Results of examinations

Clinical signs:

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

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

histopathology: non-neoplastic

mortality

Remarks on result:

other: No toxic effects were observed

2

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

gross pathology

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Remarks on result:

other: No toxic effects were observed

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Applicant's summary and conclusion

Conclusions:

No Observed Adverse Effect Level (NOAEL) for parental toxicity was considered to be 50 mg/kg/day for the females and 10 mg/kg/day for the males

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. Detailed clinical observations and neurobehavioral tests were conducted at designated intervals to assess behavior, main functions and reflexes (landing
foot splay, rectal temperature and forelimb grip strength) and to measure motor activity over a 1- and 10-minute periods. Blood samples were collected from all males of the principal groups and from all females of the toxicity groups at the end of the treatment period. At final sacrifice, 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 group. slightly lower sodium, potassium and glucose levels in males given 100 mg/kg/day, treatment-related degenerative/necrotic nephropathy in 9/10 males,while  slightly lower sodium, potassium and glucose levels in males given 50 mg/kg/day,minimal degenerative/necrotic nephropathy in 4/10 males at 50 mg/kg/day. In female slight not significant transient decrease in body weight, slight degenerative/necrotic nephropathy in 3/10 females, no other substance-induced toxicity.While  no substance-induced toxicity at these two dose-levels i.e. 10, 50 mg/kg/day. Under the conditions of this combined repeat-dose toxicity study with the reproduction/developmental toxicity screening test, the oral administration of test chemical to male and female Sprague-Dawley rats, from the pre-mating period, during mating and until sacrifice (males) or during gestation and lactation until day 4 post-partum (females), 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. 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). Based on these results, the No Observed Adverse Effect Level (NOAEL) for parental toxicity was considered to be 50 mg/kg/day for the females and 10 mg/kg/day for the males