Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Effects on fertility: Weight of evidence: Based on the experimental results on rats and mice treated with supporting substances citric acid and citric acid, sodium salt, read-across approach was applied and no toxicity to reproduction was observed in any case. The NOAEL for triacetoxyvinylsilane was calculated to be >=3022.46 mg/kg bw/day (based on no effects observed at the highest dose).

Link to relevant study records

Referenceopen allclose all

Endpoint:
one-generation reproductive toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category ). Therefore, citric acid has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Based on the experimental results obtained with the supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day (basis for effect: number of pregnancies) in rats daily treated by feed before, during, and after mating), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or greater than 3022.46 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 022.46 mg/kg bw/day
Sex:
female
Basis for effect level:
other: (Read-across approach from citric acid effect level based on test material and basis for effect: number of pregnancies)
Remarks on result:
other: (Read-across approach from citric acid based on no adverse effect observed at the highest dose tested)
Key result
Critical effects observed:
no
Based on the experimental results obtained with the analogue citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or greater than 3022.46 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 3 022.46 mg/kg bw/day
Sex:
male/female
Basis for effect level:
viability
mortality
Remarks on result:
other: (Read-across approach from citric acid effect level based on test material and no adverse effect observed at the highest dose tested)
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
Based on the experimental results obtained with the analogue citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or greater than 3022.46 mg/kg bw/day for studied effects.
Executive summary:

Based on the experimental results obtained with the analogue Citric acid (NOAEL >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or greater than 3022.46 mg/kg bw/day for studied effects.

Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Rats were fed with diets containing 1.2% citric acid (about 600 mg/kg bw/day). Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Basal diet: Casein 6.0 %, Dried full milk 10.0 %, Whole wheat flour 34.5 %, Potato flour 33.0 %, Peanut oil 6.5 %, Cod liver oil 0.5 %, Linseed oil 0.5 %, Brewer's yeast 5.0 %, Ca2(PO4)2 1.9 %, Na2HPO4 . 2H20 0.8 %, KCl 0.9 %, MgCO3 0.2 %, Na-citrate 0.1 %, various salts 0.1 %.
Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Treated rats were fed diets containing 1.2% citric acid.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Several months. Exposure began 29 weeks prior to mating and continued for a few months after mating.
Frequency of treatment:
Daily
Dose / conc.:
1.2 other: % in diet
Remarks:
1.2 % (ca. 600 mg/kg bw/day)
Basis: nominal in diet
No. of animals per sex per dose:
No data
Control animals:
not specified
Positive control:
No data
Parental animals: Observations and examinations:
Fertility of female rats.
The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
Statistics:
The statistical methods used in the evaluation of the results have been described in detail. The bilateral tail probability (p), i.e. the probability that the difference found be accidental, was calculated in each instance. The difference was considered significant, whenever p was smaller than 0.05.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
No reproductive effects were detected.
Key result
Dose descriptor:
NOAEL
Effect level:
600 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
LOAEL
Effect level:
> 600 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Critical effects observed:
no
Remarks on result:
not measured/tested
Key result
Reproductive effects observed:
no

No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.

Conclusions:
No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.
Executive summary:

A fertility test was carried out with Citric Acid on rats. Animals were fed diets containing 1.2% citric acid (about 600 mg/kg bw/day). Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.

No reproductive effects were detected. The NOAEL for reproductive effects was 600 mg/kg bw/day. The LOAEL was higher than 600 mg/kg bw/day for the same effects.

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats. Animals were fed a standard bran/oats dried milk diet. Control groups of female rats were compared to groups of female rats fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Animals were fed a standard bran/oats dried milk diet.
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Animals were treated before, during, and after mating.
Frequency of treatment:
Daily
Dose / conc.:
5 other: % in diet
Remarks:
5 % (about 2.5 g/kg bw/day)
Basis: nominal in diet
No. of animals per sex per dose:
6 female rats per group
Control animals:
yes
Positive control:
No data
Parental animals: Observations and examinations:
Number of pregnancies in rats.
Litter observations:
Number of young born, or survival of young in rats.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
not examined
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined
No effects were seen on number of pregnancies in rats.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: (number of pregnancies)
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Description (incidence and severity):
No effects were seen on number of young born, or survival of young in rats.
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no

No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.

Conclusions:
No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.
Executive summary:

This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats. Animals were fed a standard bran/oats dried milk diet. Control groups of female rats were compared to groups of female rats fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.

No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.

Endpoint:
fertility, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Rats were fed with diets containing 0.1% citric acid, sodium salt. Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Basal diet: Casein 6.0 %, Dried full milk 10.0 %, Whole wheat flour 34.5 %, Potato flour 33.0 %, Peanut oil 6.5 %, Cod liver oil 0.5 %, Linseed oil 0.5 %, Brewer's yeast 5.0 %, Ca2(PO4)2 1.9 %, Na2HPO4 . 2H20 0.8 %, KCl 0.9 %, MgCO3 0.2 %, Na-citrate 0.1 %, various salts 0.1 %.
Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
Treated rats were fed diets containing 0.1% citric acid, sodium salt.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Several months. Exposure began 29 weeks prior to mating and continued for a few months after mating.
Frequency of treatment:
Daily
Dose / conc.:
0.1 other: % in diet
Remarks:
0.1 % (ca. 50 mg/kg bw/day)
Basis:nominal in diet
No. of animals per sex per dose:
No data
Control animals:
not specified
Positive control:
No data
Parental animals: Observations and examinations:
Fertility of female rats.
The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.
Statistics:
The statistical methods used in the evaluation of the results have been described in detail. The bilateral tail probability (p), i.e. the probability that the difference found be accidental, was calculated in each instance. The difference was considered significant, whenever p was smaller than 0.05.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
not examined
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
No reproductive effects were detected.
Key result
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
LOAEL
Effect level:
> 50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Critical effects observed:
no
Remarks on result:
not measured/tested
Key result
Reproductive effects observed:
no

No reproductive effects were detected. The NOAEL for reproductive effects was 50 mg/kg bw/day. The LOAEL was greater than

50 mg/kg bw/day.

Conclusions:
No reproductive effects were detected. The NOAEL for reproductive effects was 50 mg/kg bw/day. The LOAEL was greater than 50 mg/kg bw/day.
Executive summary:

A fertility test was carried out with Citric Acid on rats. Animals were fed diets containing 0.1% citric acid, sodium salt (ca. 50 mg/kg bw/day). Exposure began 29 weeks prior to mating and continued for a few months after mating. The reproduction of the rats was investigated when they were 32 weeks old and had received the diets for 29 weeks. Eleven weeks later the same animals were mated again.

No reproductive effects were detected. The NOAEL for reproductive effects was 50 mg/kg bw/day. The LOAEL was greater than 50 mg/kg bw/day.

Endpoint:
fertility, other
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category ). Therefore, citric acid has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Based on the experimental results obtained with the supporting substance citric acid on rats daily treated by feed for several months (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 725.39 mg/kg bw/day, and LOAEL higher than 725.39 mg/kg bw/day for reproductive effects.
Key result
Dose descriptor:
NOAEL
Effect level:
725.39 mg/kg bw/day
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: (Read-across approach from citric acid effect level based on test material and no adverse effect observed at the highest dose tested)
Key result
Dose descriptor:
LOAEL
Effect level:
> 725.39 mg/kg bw/day
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: (Read-across approach from citric acid effect level based on test material and no adverse effect observed at the highest dose tested)
Key result
Critical effects observed:
no
Remarks on result:
not measured/tested
Key result
Reproductive effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance citric acid on rats daily treated by feed for several months (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 725.39 mg/kg bw/day, and LOAEL higher than 725.39 mg/kg bw/day for reproductive effects.
Executive summary:

Based on the experimental results obtained with the supporting substance citric acid on rats daily treated by feed for several months (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 725.39 mg/kg bw/day, and LOAEL higher than 725.39 mg/kg bw/day for reproductive effects.

Endpoint:
fertility, other
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and sodium citrate are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and sodium citrate in the same category). Therefore, sodium citrate has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Based on the experimental results obtained with the supporting substance citric acid, sodium salt, on rats daily treated by feed for several months (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 51.44 mg/kg bw/day, and LOAEL greater than 51.44 mg/kg bw/day for reproductive effects.
Key result
Dose descriptor:
NOAEL
Effect level:
54.24 mg/kg bw/day
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: (Read-across approach from sodium citrate effect level based on test material and no adverse effect observed at the highest dose tested)
Key result
Dose descriptor:
LOAEL
Effect level:
> 54.24 mg/kg bw/day
Sex:
female
Basis for effect level:
reproductive performance
Remarks on result:
other: (Read-across approach from sodium citrate effect level based on test material and no adverse effect observed at the highest dose tested)
Key result
Critical effects observed:
no
Remarks on result:
not measured/tested
Key result
Reproductive effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance citric acid, sodium salt, on rats daily treated by feed for several months (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 54.24 mg/kg bw/day, and LOAEL greater than 54.24 mg/kg bw/day for reproductive effects.
Executive summary:

Based on the experimental results obtained with the supporting substance citric acid, sodium salt, on rats daily treated by feed for several months (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be 54.24 mg/kg bw/day, and LOAEL greater than 54.24 mg/kg bw/day for reproductive effects.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
3 022.46 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Three fertily studies, one of them including a one-generation study, are available with Klimisch score =2 in a weight of evidence approach. The overall quality of the database was determined as appropriate for assessment.
Additional information

Weight of evidence:

 

Read-across from experimental results with citric acid and citric acid, sodium salt:

 

In the study by Bonting et. al., 1956 (reliability 2), a fertility test was carried out with citric acid on female rats (daily treated by feed for several months). No reproductive effects were observed. Based on the experimental results obtained with the supporting substance citric acid (NOAEL for reproductive effects = 600 mg/kg bw/day; LOAEL > 600 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to be 725.39 mg/kg bw/day, and LOAEL > 725.39 mg/kg bw/day for reproductive effects.

 

In the study performed by Wright et. al., 1976 (reliability 2), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats was carried out. Based on the experimental results obtained with the supporting substance citric acid (NOAEL P, F1 >= 2500 mg/kg bw/day in rats (basis for effect: number of pregnancies, number of young born, or survival of young animals)), the read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to ≥ than 3022.46 mg/kg bw/day for studied effects.

 

In the same study performed by Bonting et. al. 1956 (reliability 2), a fertility test was carried out but with citric acid, sodium salt on female rats (daily treated by feed for several months). No reproductive effects were detected. Based on the experimental results obtained with the supporting substance citric acid, sodium salt (NOAEL for reproductive effects = 50 mg/kg bw/day; LOAEL > 50 mg/kg bw/day for the same effects), the read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to be 54.24 mg/kg bw/day, and LOAEL > than 54.24 mg/kg bw/day for reproductive effects.

Key value for chemical safety assessment:

According to the experimental results with supporting substances citric acid and citric acid, sodium salt, no toxicity to reproduction was observed in any case. Therefore and based on read-across approaches, the NOAEL for triacetoxyvinylsilane was calculated to be >= 3022.46 mg/kg bw/day, based on no effects observed at the highest dose tested.

Effects on developmental toxicity

Description of key information

Developmental toxicity/Teratogenicity: Weight of evidence: Based on the experimental results on rats, mice, and rabbits treated with supporting substances acetic acid, sodium acetate, citric acid and calcium formate, read-across approach was applied and no maternal nor developmental toxicity was observed in treated animals exposed to high doses of these substances.  The NOAEL for triacetoxyvinylsilane was calculated to be >= 2062.90 mg/kg bw/day (based on no effects observed at the highest dose).

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with Acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for maternal toxicity), the read-across approach is applied and the NOAEL for maternal toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with Acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for developmental toxicity), the read-across approach is applied and the NOAEL for developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: Fetuses toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with Acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with Acetic acid in rat (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
A FDA study
Principles of method if other than guideline:
Following mating, adult female albino CD-1 mice were dosed daily by oral intubation beginning on day 6 of gestation. Animals were observed daily and body weights recorded for 10 days. On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.
GLP compliance:
no
Limit test:
no
Species:
mouse
Strain:
CD-1
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 10 days (beginning on day 6 of gestation).
Frequency of treatment:
Daily
Duration of test:
17 days
Dose / conc.:
16 mg/kg bw/day (nominal)
Dose / conc.:
74 mg/kg bw/day (nominal)
Dose / conc.:
345 mg/kg bw/day (nominal)
Dose / conc.:
1 600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Only female animals were used.
Control animals:
yes, concurrent no treatment
Maternal examinations:
Animals were observed daily and body weights recorded for 10 days.
Ovaries and uterine content:
On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites and resorption sites was recorded.
Fetal examinations:
After cesarea, the numbers of live and dead fetuses was recorded.
General external and internal examinations were also made of the dams.
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effects on maternal survival were observed at doses up to 1600 mg/kg bw/day.
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
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:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Number of abortions:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
External malformations:
not specified
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in skeletal tissues of the test groups did not differ from the number occurring in the controls.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in soft tissues of the test groups did not differ from the number occurring in the controls.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Fetuses toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no

No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Conclusions:
No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.
Executive summary:

Following mating, adult female albino CD-1 mice were dosed daily by oral intubation beginning on day 6 of gestation. Tested doses were 0, 16, 74, 345, and 1600 mg/kg bw/day. Animals were observed daily and body weights recorded for 10 days. On day 17, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.

No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
A FDA study.
Principles of method if other than guideline:
Following mating, adult female albino rats (Wistar) were dosed daily by oral intubation beginning on day 6 of gestation. Animals were observed daily and body weights recorded. On day 20, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposure period: 10 days (beginning on day 6 of gestation).
Frequency of treatment:
Daily
Duration of test:
14 days
Dose / conc.:
16 mg/kg bw/day (nominal)
Dose / conc.:
74 mg/kg bw/day (nominal)
Dose / conc.:
345 mg/kg bw/day (nominal)
Dose / conc.:
1 600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Only female animals were used.
Control animals:
yes, concurrent no treatment
Maternal examinations:
Animals were observed daily and body weights recorded.
Ovaries and uterine content:
On day 20, Caesarian sections were performed on all dams and the numbers of implantation sites and resorption sites was recorded.
Fetal examinations:
After cesarea, the numbers of live and dead fetuses was recorded.
General external and internal examinations were also made of the dams.
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effects on maternal survival were observed at doses up to 1600 mg/kg bw/day.
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
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:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Number of abortions:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effects on nidation survival were observed at doses up to 1600 mg/kg bw/day.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
External malformations:
not specified
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in skeletal tissues of the test groups did not differ from the number occurring in the controls.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in soft tissues of the test groups did not differ from the number occurring in the controls.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: fetuses toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no

No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Conclusions:
No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.
Executive summary:

Following mating, adult female albino rats (Wistar) were dosed daily by oral intubation beginning on day 6 of gestation. Tested doses were 0, 16, 74, 345, and 1600 mg/kg bw/day. Animals were observed daily and body weights recorded. On day 20, Caesarian sections were performed on all dams and the numbers of implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the dams.

No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
A FDA study.
Principles of method if other than guideline:
Following artificial insemination, adult Dutch-belted female rabbits were dosed daily by oral intubation beginning on day 6 of gestation. Animals were observed daily and body weights recorded. On day 29, Caesarian sections were performed on all does and the numbers of corpora lutea, implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the does.
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
Dutch
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Female rabbits were artificially inseminated.
Duration of treatment / exposure:
Exposure period: 13 days (beginning on day 6 of gestation).
Frequency of treatment:
Daily
Duration of test:
23 days
Dose / conc.:
16 mg/kg bw/day (nominal)
Dose / conc.:
74 mg/kg bw/day (nominal)
Dose / conc.:
345 mg/kg bw/day (nominal)
Dose / conc.:
1 600 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Only female animals were used.
Control animals:
yes, concurrent no treatment
Maternal examinations:
Animals were observed daily and body weights recorded.
Ovaries and uterine content:
On day 29, Caesarian sections were performed on all does and the numbers of corpora lutea, implantation sites and resorption sites was recorded.
Fetal examinations:
After cesarea, the numbers of live and dead fetuses was recorded.
General external and internal examinations were also made of the does.
Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effects on maternal survival were observed at doses up to 1600 mg/kg bw/day.
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
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:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed
Number of abortions:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
No effects on nidation were observed at doses up to 1600 mg/kg bw/day.
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects on fetal survival were observed at doses up to 1600 mg/kg bw/day.
External malformations:
not specified
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in skeletal tissues of the test groups did not differ from the number occurring in the controls.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The number of abnormalities seen in soft tissues of the test groups did not differ from the number occurring in the controls.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: fetuses toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no

No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Conclusions:
No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.
Executive summary:

Following artificial insemination, adult Dutch-belted female rabbits were dosed daily by oral intubation beginning on day 6 of gestation. Tested doses were 0, 16, 74, 345, and 1600 mg/kg bw/day. Animals were observed daily and body weights recorded. On day 29, Caesarian sections were performed on all does and the numbers of corpora lutea, implantation sites, resorption sites, and live and dead fetuses was recorded. General external and internal examinations were also made of the does.

No effects on nidation or on maternal or fetal survival at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
No data on GLP. The publication provides scientific valid information as an in vivo teratology screen.
Principles of method if other than guideline:
Pregnant CD-1 mice were generally treated by oral gavage on days 8-12 of gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. Day 20 of gestation was considered postnatal day 1 (PD1). On PD1 and 3, the litters were counted and weighed as a unit.
GLP compliance:
not specified
Limit test:
yes
Species:
mouse
Strain:
CD-1
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Time-pregnant female CD-1 mice, approximately 60 d old. The day of sperm plug identification was considered day 1 of pregnancy .
Duration of treatment / exposure:
On Days 8-12 of gestation.
Frequency of treatment:
Daily
Duration of test:
Day 20 of gestation was considered postnatal day 1 (PD1). On PD1 and 3, the litters were counted and weighed as a unit.
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
Control: 40 females
Sodium acetate 1000 mg/kg bw/day: 30 females
Control animals:
yes
Maternal examinations:
Mortality, pregnancy and resorption
Fetal examinations:
Mortality and body weight.
Statistics:
Data analysis was performed using the General Linear Models procedure on SAS. When a significant treatment effect was detected by analysis of variance, individual group means were compared using Student's t-test on least-squares means. Since the a priori hypothesis was that treatments could only reduce litter size, a one-tailed test was used for that variable. The number of live pups on PD1 was used as a covariate in the analysis of pup weights.
Clinical signs:
not specified
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not specified
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
not specified
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
not specified
Skeletal malformations:
not specified
Visceral malformations:
not specified
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: Neonatal effects
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

No maternal toxicity and no neonatal effects were observed at a dose level of 1000 mg/kg bw/day.

Conclusions:
No maternal toxicity and no neonatal effects were observed at a dose level of 1000 mg/kg bw/day.
Executive summary:

Pregnant CD-1 mice were generally treated by oral gavage on days 8-12 of gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. Day 20 of gestation was considered postnatal day 1 (PDI). On PD1 and 3, the litters were counted and weighed as a unit.

No maternal toxicity and no neonatal effects (mortality and body weight) were observed at a dose level of 1000 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
A three-generation drinking water study at 0 or 200 mg/kg bw/day Calcium Formate in the drinking water was performed in Wistar rats. The duration of the test was ca. 3 years. At the beginning of the test, 8 males and 24 females in the treated group, and 8 males and 8 females in the control group were used. Number, weight and length of offspring were examined. A portion of the offspring was also sacrificed shortly after birth for evaluation of developmental toxicity.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 160-200 g
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data
Duration of treatment / exposure:
A three-generation study.
Frequency of treatment:
Daily
Duration of test:
ca. 3 years
Dose / conc.:
200 mg/kg bw/day (nominal)
Remarks:
Basis: nominal in water
No. of animals per sex per dose:
At the beginning of the test:
8 males and 24 females in the treated group
8 males and 8 females in the control group
Control animals:
yes
Fetal examinations:
Number, weight and length of offspring were examined.
A portion of the offspring was also sacrificed shortly after birth for evaluation of developmental toxicity.
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Details on maternal toxic effects:
No effects on fertility (up to 3 generations) were observed.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
weight of offspring did not differ in treated animals from controls.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Weight of offspring did not differ in treated animals from controls.
The growth of treated offspring was similar to controls.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
Number of offspring did not differ in treated animals from controls.
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
Weight and length of offspring did not differ in treated animals from controls.
The growth of treated offspring was similar to controls.
Changes in postnatal survival:
not specified
External malformations:
not specified
Skeletal malformations:
no effects observed
Description (incidence and severity):
No statistical differences in bone abnormalities were found.
Visceral malformations:
no effects observed
Description (incidence and severity):
No statistical differences in organ abnormalities were found.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Localisation:
other: organ and skeletal tissues
Key result
Developmental effects observed:
no

The NOAEL for maternal and developmental toxicity was equal or higher than 200 mg/kg bw/day.

Conclusions:
The NOAEL for maternal and developmental toxicity was equal or higher than 200 mg/kg bw/day.
Executive summary:

A three-generation drinking water study at 0 or 200 mg/kg bw/day Calcium Formate in the drinking water was performed in Wistar rats. The duration of the test was ca. 3 years. At the beginning of the test, 8 males and 24 females in the treated group, and 8 males and 8 females in the control group were used.

No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls.A portion of the offspring was also sacrificed shortly after birth for evaluation of developmental toxicity. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls.

The NOAEL for maternal and developmental toxicity was equal or higher than 200 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
One-generation study: This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats. Animals were fed a standard bran/oats dried milk diet. Control groups of female rats were compared to groups of female rats fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Animals were fed a standard bran/oats dried milk diet.
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Animals were treated before, during, and after mating.
Frequency of treatment:
Daily
Duration of test:
No data
Dose / conc.:
5 other: % in diet
Remarks:
about 2.5 g/kg bw/day
Basis: nominal in diet
No. of animals per sex per dose:
6 female animals per group
Control animals:
yes
Maternal examinations:
Number of pregnancies.
Fetal examinations:
Number of young born, or survival of young in rats.
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
No effects were seen on number of pregnancies in rats.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
not examined
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects were seen on number of young born, or survival of young in rats.
Changes in sex ratio:
not examined
Changes in litter size and weights:
not examined
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects were seen on number of young born, or survival of young in rats.
External malformations:
not examined
Skeletal malformations:
not examined
Visceral malformations:
not examined
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.

Conclusions:
No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.
Executive summary:

This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the rats. Animals were fed a standard bran/oats dried milk diet. Control groups of female rats were compared to groups of female rats fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.

No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats with ca. 2.5 g/kg bw/day, compared to controls.

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
One-generation study: This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of mice. Animals were fed a standard bran/oats dried milk diet. Control groups of female mice were compared to groups of female mice fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.
GLP compliance:
no
Limit test:
yes
Species:
mouse
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Animals were fed a standard bran/oats dried milk diet.
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Animals were treated before, during, and after mating.
Frequency of treatment:
Daily
Duration of test:
No data
Dose / conc.:
5 other: % in diet
Remarks:
about 2.5 g/kg bw/day
Basis: nominal in diet
No. of animals per sex per dose:
6 female animals per group
Control animals:
yes
Maternal examinations:
Number of pregnancies.
Fetal examinations:
Number of young born, or survival of young in mice.
Clinical signs:
not examined
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
not specified
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
No effects were seen on number of pregnancies in mice.
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
not examined
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
No effects were seen on number of young born, or survival of young in mice.
Changes in sex ratio:
not examined
Changes in litter size and weights:
not examined
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
No effects were seen on number of young born, or survival of young in mice.
External malformations:
not examined
Skeletal malformations:
not examined
Visceral malformations:
not examined
Other effects:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: No adverse effect observed at the highest dose tested
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no

No effects were seen on number of pregnancies, number of young born, or survival of young in treated mice with ca. 2.5 g/kg bw/day, compared to controls.

Conclusions:
No effects were seen on number of pregnancies, number of young born, or survival of young in treated mice with ca. 2.5 g/kg bw/day, compared to controls.
Executive summary:

This study describes an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of mice. Animals were fed a standard bran/oats dried milk diet. Control groups of female mice were compared to groups of female mice fed diets containing 5% citric acid (about 2.5 g/kg bw/day) before, during, and after mating. Six animals were in each group for the reproductive studies.

No effects were seen on number of pregnancies, number of young born, or survival of young in treated mice with ca. 2.5 g/kg bw/day, compared to controls.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with Acetic acid in mouse (NOAEL >= 1600 mg/kg bw/day for maternal toxicity), the read-across approach is applied and the NOAEL for maternal toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with Acetic acid in mouse (NOAEL >= 1600 mg/kg bw/day for developmental toxicity), the read-across approach is applied and the NOAEL for developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: (Read-across approach from acetic acid effect level based on test material and basis for effect: overall effects)
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with Acetic acid in mouse (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with Acetic acid in mouse (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with Acetic acid in rabbit (NOAEL >= 1600 mg/kg bw/day for maternal toxicity), the read-across approach is applied and the NOAEL for maternal toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: developmental toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with Acetic acid in rabbit (NOAEL >= 1600 mg/kg bw/day for developmental toxicity), the read-across approach is applied and the NOAEL for developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 2 062.9 mg/kg bw/day
Basis for effect level:
other: fetuses toxicity
Remarks on result:
other: (Read-across approach from acetic acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
effects observed, non-treatment-related
Localisation:
other: soft and skeletal tissues
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with Acetic acid in rabbit (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with Acetic acid in rabbit (NOAEL >= 1600 mg/kg bw/day for both maternal and developmental toxicity), the read-across approach is applied and the NOAEL for maternal and developmental toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 2062.90 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and its salts are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and acetates as a subcategory). Therefore, sodium acetate has comparable values with acetic acid and the target substance methylsilanetriyl triacetate.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with Sodium acetate in mouse (NOAEL >= 1000 mg/kg bw/day for maternal toxicity, basis for effects: mortality, pregnancy and resorption), the read-across approach is applied and the NOAEL for maternal toxicity of triacetoxyvinylsilane is calculated to be equal or greater than 943.84 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 943.84 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from sodium acetate based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with Sodium acetate in mouse (NOAEL >= 1000 mg/kg bw/day for neonatal effects, basis for effects: mortality and body weight), the read-across approach is applied and the NOAEL for neonatal effects of triacetoxyvinylsilane is calculated to be equal or greater than 943.84 mg/kg bw/day.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 943.84 mg/kg bw/day (actual dose received)
Basis for effect level:
other: Neonatal effects
Remarks on result:
other: (Read-across approach from sodium acetate based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with Sodium acetate in mouse (NOAEL >= 1000 mg/kg bw/day for maternal toxicity, basis for effects: mortality, pregnancy and resorption; and NOAEL >= 1000 mg/kg bw/day for neonatal effects, bases for effects: mortality and body weight), the read-across approach is applied and the NOAEL both for maternal toxicity and neonatal effects of triacetoxyvinylsilane is calculated to be equal or greater than 943.84 mg/kg bw/day.
Executive summary:

Based on the experimental results obtained with Sodium acetate in mouse (NOAEL >= 1000 mg/kg bw/day for maternal toxicity, basis for effects: mortality, pregnancy and resorption; and NOAEL >= 1000 mg/kg bw/day for neonatal effects, bases for effects: mortality and body weight), the read-across approach is applied and the NOAEL both for maternal toxicity and neonatal effects of triacetoxyvinylsilane is calculated to be equal or greater than 943.84 mg/kg bw/day.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and calcium formate are analogue substances because of their close structural relationship. Therefore, calcium formate has comparable values with acetic acid and the target substance methylsilanetriyl triacetate.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with the supporting substance Calcium formate in rats (NOAEL >= 200 mg/kg bw/day for maternal toxicity, basis for effect: fertility), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 238.02 mg/kg bw/day for maternal toxicity.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 238.02 mg/kg bw/day
Basis for effect level:
other: maternal developmental toxicity
Remarks on result:
other: (Read-across approach from calcium formate based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with the supporting substance Calcium formate in rats (NOAEL >= 200 mg/kg bw/day for developmental toxicity,basis for effect: overall effects), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 238.02 mg/kg bw/day for developmental toxicity.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 238.02 mg/kg bw/day
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: (Read-across approach from calcium formate based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Localisation:
other: organ and skeletal tissues
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with the supporting substance Calcium formate in rats (NOAEL >= 200 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: fertility and overall effects respectively), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 238.02 mg/kg bw/day for both maternal and developmental toxicity.
Executive summary:

Based on the experimental results obtained with the supporting substance Calcium formate in rats (NOAEL >= 200 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: fertility and overall effects respectively), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 238.02 mg/kg bw/day for both maternal and developmental toxicity.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category ). Therefore, citric acid has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.

Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with the analogue Citric acid in rats (NOAEL >= 2500 mg/kg bw/day for maternal toxicity, basis for effect: number of pregnancies), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for studied effects.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 022.46 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from citric acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with the analogue Citric acid in rats (NOAEL >= 2500 mg/kg bw/day for developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for studied effects.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 022.46 mg/kg bw/day
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: (Read-across approach from citric acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with the analogue Citric acid in rats (NOAEL >= 2500 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxysilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for both maternal and developmental toxicity.
Executive summary:

Based on the experimental results obtained with the analogue Citric acid in rats (NOAEL >= 2500 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for both maternal and developmental toxicity.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Triacetoxyvinylsilane undergoes rapid hydrolysis in aqueous to acetic acid and the corresponding trisilanols. Trisilanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to the acetic acid and their values are comparable. Acetic acid and citric acid are grouped together because of their close structural relationship (US EPA officially recognises acetic acid and citric acid in the same category ). Therefore, citric acid has comparable values with acetic acid and the target substance triacetoxyvinylsilane.
See attached the reporting format.
Reason / purpose for cross-reference:
read-across source
Details on maternal toxic effects:
Based on the experimental results obtained with the analogue Citric acid in mouse (NOAEL >= 2500 mg/kg bw/day for maternal toxicity, basis for effect: number of pregnancies), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for studied effects.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 022.46 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: (Read-across approach from citric acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Details on embryotoxic / teratogenic effects:
Based on the experimental results obtained with the analogue Citric acid in mouse (NOAEL >= 2500 mg/kg bw/day for developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for studied effects.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 3 022.46 mg/kg bw/day
Basis for effect level:
other: Developmental toxicity
Remarks on result:
other: (Read-across approach from citric acid based on no adverse effect observed at the highest dose tested)
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the experimental results obtained with the analogue Citric acid in mouse (NOAEL >= 2500 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxyvinylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for both maternal and developmental toxicity.
Executive summary:

Based on the experimental results obtained with the analogue Citric acid in mouse (NOAEL >= 2500 mg/kg bw/day for both maternal and developmental toxicity, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL with the substance triacetoxyviniylsilane is calculated to be equal or higher than 3022.46 mg/kg bw/day for both maternal and developmental toxicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 062.9 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Four teratology studies, one of them performed on rats, mice and rabbits, and another one in rats and mice, are available. Three studies have a Klimisch score = 2 and one has a Klimisch score = 4 in a weight of evidence approach. The overall quality of the database was determined as appropriate for assessment.
Additional information

Weight of evidence:

 

Read-across from experimental results with acetic acid, sodium acetate, calcium formate and citric acid:

 

In the study by Food and Drug Research Laboratories, 1974 (reliability 2), following mating, adult female mice, rats and rabbits were dosed daily for 17 days by oral intubation with acetic acid. No effects on nidation or on maternal or fetal survival were observed at doses up to 1600 mg/kg bw/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Based on the experimental results with supporting substance acetic acid (NOAEL >= 1600 mg/kg bw/day for maternal and developmental toxicity), the read-across approach was applied and the NOAEL of triacetoxyvinylsilane for maternal and developmental toxicity was calculated to be >= 2062.90 mg/kg bw/day.

 

In the study by Kavlock et. al., 1987 (reliability 2), pregnant mice were generally treated by oral gavage during gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. No maternal toxicity and no neonatal effects (mortality and body weight) were observed at the treatment dose level of 1000 mg/kg bw/day. Based on the experimental results obtained with supporting substance sodium acetate (NOAEL >= 1000 mg/kg bw/day) for maternal and neonatal toxicity), read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to by >= 943.84 mg/kg bw/day.

 

In the study by Malorny, 1969 (reliability 2) a three-generation drinking water study with calcium formate in the drinking water was performed in Wistar rats during ca. 3 years. No effects on fertility were observed. Number, weight and length of offspring did not differ in treated animals from controls. No statistical differences in organ or bone abnormalities were found. The growth of treated offspring was similar to controls. Based on experimental results on supporting substance calcium formate (NOAEL for maternal and developmental toxicity >= 200 mg/kg bw/day), the read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to be >= 238.02 mg/kg bw/day for maternal and developmental toxicity.

 

In the study by Wright et. al. 1976 (reliability 4), an experiment designed to examine the effect of a 5% dietary supplement of citric acid on the reproductive capacity of the mice and rats was carried out. No effects were seen on number of pregnancies, number of young born, or survival of young in treated rats, compared to controls. Based on the experimental results from supporting substance citric acid (NOAEL >= 2500 mg/kg bw/day, basis for effect: number of pregnancies, number of young born, or survival of young animals), the read-across approach was applied and the NOAEL for triacetoxyvinylsilane was calculated to be >= 3022.46 for studied effects.

Key value for chemical safety assessment:

 

According to the experimental results with supporting substances acetic acid, sodium acetate, sodium formate and citric acid on mice, rats and rabbits, no maternal or developmental toxicity was seen in treated animals exposed to high doses of these substances.Therefore and based on read-across approaches, the NOAEL for triacetoxyvinylsilane was calculated to be >= 2062.90 mg/kg bw/day, based on no effects observed at the highest dose tested in a reliable study (the NOAEL >= 3022.46 mg/kg bw/day was obtained in the read-across approach from a not assignable study, Klimisch 4, and was excluded as a key value for chemical safety assessment).

Justification for classification or non-classification

Based on available data and according to the CLP Regulation, triacetoxyvinylsilane is not classified as dangerous for reproduction.

Additional information