Registration Dossier

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
19.09.2002 to 30.04.2004
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP, and is therefore considered to be reliability 1. Read-across of the result is considered to be reliability 2.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: OECD 422
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Reference substance name:
Tetraethyl orthosilicate
EC Number:
201-083-8
EC Name:
Tetraethyl orthosilicate
Cas Number:
78-10-4
IUPAC Name:
tetraethyl orthosilicate

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, France.
- Age at study initiation: Males: 8 weeks; Females: 10 weeks.
- Weight at study initiation: Males: 283-339 g; Females: 213-285 g.
- Fasting period before study: None
- Housing: Individually in suspended wire-mesh cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: 9-11 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): 50 ±20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 30.09.2002 To: 9-21.11.2002 for principal and toxicity groups. From: 01.04.2004 to 30.4.2004 for complementary groups.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The test substance was mixed with the required quantity of vehicle at concentrations of 3.33, 16.66 and 33.33 mg/ml. The dosage forms were performed as follows: the required quantity of test substance was weighed into an appropriate container; 75% of the final volume of the vehicle was added and the preparation was homogenised with a magnetic stirrer. Sufficient vehicle was thereafter added to make the solutions up to the required volume. The vehicle for the control group was measured first, followed by preparation of the low and intermediate, then theh high dose forms to avoid contamination. Solutions were kept for up to 9 days.


VEHICLE
- Justification for use and choice of vehicle (if other than water): None given
- Concentration in vehicle: 3.33, 16.66 and 33.33 mg/ml
- Amount of vehicle (if gavage): Various depending on concentration
- Lot/batch no. (if required): 81K2204 and 062K0006
- Purity: No data
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: Overnight
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy.
- Each female was placed with the same male until mating occurred or 14 days elapsed.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): No data
Duration of treatment / exposure:
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). 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 females received the test item and a fourth group received the vehicle under the same experimental conditions as males of the principal groups for at least 4 weeks in total.
Frequency of treatment:
daily
Duration of test:
Up to 53 days
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 50 and 100 mg/kg bw/day
Basis:

No. of animals per sex per dose:
Ten
Control animals:
yes, concurrent vehicle
Details on study design:
Sex: male/female
Duration of test: up to 53 days
- Dose selection rationale: Based on a seven day range-finding study.
- Rationale for animal assignment (if not random): Random

Examinations

Maternal examinations:
See Section 7.5.1.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: No
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
Fetal examinations:
- External examinations: Yes, when born, but not at sacrifice.
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No
Statistics:
Yes, various methods depending on endpoint.
Indices:
Live birth index: No.live born pups/No. of pups delivered x100.
Viability index (on day 4 post-partum): No. surviving pups on day 4 post-partum/No. live born pups x 100.
Historical control data:
None reported

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Renal tubular nephropathy in the toxicity group females.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No effects.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a good quality OECD 422 study conducted to GLP (reliability score 1) the NOAEL for developmental effects in offspring from rats treated with tetraethylorthosilicate was at least 100 mg/kg bw/d, the highest dose tested. The NOAEL for the dams was 50 mg/kg bw/day based on tubular nephropathy at 100 mg/kg bw/day in the toxicity group females.
Executive summary:

In a good quality OECD 422 study conducted to GLP (reliability score 1) the NOAEL for developmental effects in offspring from rats treated with tetraethylorthosilicate was at least 100 mg/kg bw/d, the highest dose tested. The NOAEL for the dams was 50 mg/kg bw/day based on tubular nephropathy at 100 mg/kg bw/day in the toxicity group females.