[3-(2,3-epoxypropoxy)propyl]diethoxymethylsilane

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.10.1981 to 18.02.1982

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

Limited details on test substance, dosing during organogenesis only.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

[3-(2,3-epoxypropoxy)propyl]trimethoxysilane

EC Number:

219-784-2

EC Name:

[3-(2,3-epoxypropoxy)propyl]trimethoxysilane

Cas Number:

2530-83-8

Molecular formula:

C9H20O5Si

IUPAC Name:

Trimethoxy-[3-(oxiran-2-ylmethoxy)propyl]silane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:2
- Length of cohabitation: No data
- Further matings after two unsuccessful attempts: No data
- Verification of same strain and source of both sexes: No data
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

Test substance exposure occurred during the primary period of organogenesis, i.e., gestation days 6-15.

Frequency of treatment:

Once per day on gestation days 6-15

Duration of test:

15 days (dams killed on gestation day 20)

No. of animals per sex per dose:

20 females

Control animals:

other: yes, with water only.

Details on study design:

Sex: female
Duration of test: 3 weeks

Examinations

Statistics:

Fetal body weights and body measurements, maternal body weights, weights of the maternal livers and uteri and food consumption data were analyzed statistically by a one-way analysis of variance and Dunnett's test (Steel and Torrie, 1960).  The Wilcoxon test as modified by Haseman and Hoel (1974) was used to evaluate incidences of fetal resorptions and alterations.  Other incidence data were analyzed statistically by the Fischer exact test (Seigel, 1956).  The level of significance chosen for all cases was p < 0.05.

Historical control data:

The incidence of malformations and variations in the historical controls is not available. These data were not collected by the laboratory that conducted this study.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: No adverse effects observed.

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

There were no test substance-related mortalities.  One rat (subsequently replaced) in the 50 mg/kg/day group died as
the result of dosing trauma.  There were no test substance-related effects on clinical condition, behaviour,
body weight, body weight gain or food consumption.  No effects on liver or gravid uterine weight were observed.  No
effects on the number of implantation sites or corpora lutea per dam were observed.  The incidence of pregnancy was not
affected by treatment with the test substance; all rats were confirmed to be pregnant at the gestation day 20
(laparo hysterectomies).  No adverse effects on the number of live fetuses per litter, mean litter size, sex ratio, fetal
body weight or crown-rump length were observed.  The incidence of fetal resorptions was not altered by test
substance administration.  No external, visceral or skeletal alterations were observed among test substance-treated rats
at an incidence that was statistically different from the control group.  When considered collectively, the incidence
of total major malformations observed in the external, soft tissue or skeletal examinations was not significantly
different among the treated groups as compared to the control group.  No major malformations were observed among
litters of rats that received either 500 or 1000 mg/kg/day of the test substance.  The sporadic variations and
malformations seen occurred at an incidence comparable to a historical control incidence for Sprague-Dawley rats
reported in the literature.

Applicant's summary and conclusion

Conclusions:

In a good quality developmental toxicity study (reliability score 1), similar to OECD 414 and GLP, 3-glycidoxypropyltrimethoxysilane exhibited no adverse effects on the maternal animals or the offspring. The NOAEL for maternal and developmental toxicity was at least 1000 mg/kg bw/day.

Executive summary:

In a good quality developmental toxicity study (reliability score 1), similar to OECD 414 and GLP, 3-glycidoxypropyltrimethoxysilane exhibited no adverse effects on the maternal animals or the offspring. The NOAEL for maternal and developmental toxicity was at least 1000 mg/kg bw/day.