Synthetic amorphous magnesium silicate, with molar ratio (SiO2:MgO) range of 1.4-4

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Circa 1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, basic data given, acceptable for assessment, although deficiencies in documentation of test design and results. Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, basic data given, acceptable for assessment, although deficiencies in documentation of test design and results. Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

Syloid 244: CAS-Name: Silica gel, cryst.-free;
CAS-No. 112926-00-8

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation:
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: single
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: water suspension

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No information

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy

Duration of treatment / exposure:

from day 6 to day 15 of gestation

Frequency of treatment:

once daily

Duration of test:

gestation day 17: sacrifice of all dams by caesarean section

Remarks:

Doses / Concentrations:
0, 13.4, 62.3, 289 and 1340 mg/kg bw/d
Basis:

No. of animals per sex per dose:

21 - 26 pregnant dams

Control animals:

yes

other: positive control dosed with Aspirin, 150 mg/kg bw/d

Details on study design:

- Dose selection rationale: no data

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 11, 15, and 17


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: in particular urogenital tract

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 1/3 per litter
- Head examinations: yes

Statistics:

no data

Indices:

No data

Historical control data:

no data

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
The administration of up to 1340 mg/kg (body weight) of the test material to pregnant mice for 
10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 340 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.   

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 340 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

The administration of up to 1340 mg/kg (body weight) of the test material to pregnant mice for 

10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ
from the number occurring spontaneously in the sham-treated controls.
  

Conclusions:

The administration of up to 1340 mg/kg (body weight) of the test material to pregnant mice for 
10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.  The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Executive summary:

A study with Syloid 244 was conducted based on OECD test guideline 414. Mice were dosed with 0,  13.4,  62.3,  289 and  1340 mg/kg bw/d.

The administration of up to 1340 mg/kg (body weight) of the test material to pregnant mice for 

10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.  The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The NOAEL was determined to be 1340 mg/kg bw/day.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, basic data given, acceptable for assessment, although deficiencies in documentation of test design and results. Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

Syloid 244: CAS-Name: Silica gel, cryst.-free;
CAS-No. 112926-00-8

Species:

rabbit

Strain:

Dutch

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: single
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: water suspension

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No information

Details on mating procedure:

- Impregnation procedure: artificial insemination
- Proof of pregnancy: no data [day 0 = day of artificial insemination]

Duration of treatment / exposure:

from day 6 to day 18 of gestation

Frequency of treatment:

once daily

Duration of test:

day 29: sacrifice of does by caesarean section

Remarks:

Doses / Concentrations:
0, 16.0, 74.3, 345 and 1600 mg/kg bw/d
Basis:

No. of animals per sex per dose:

10, 12, 11, 14, and 13 pregnant animals, respectively for 0, 16.0, 74.3, 345 and 1600 mg/kg bw/d groups

Control animals:

yes

other: pos. control dosed with 6-aminonicotinamide, 2.5 mg/(kg bw *d)

Details on study design:

No information available

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 12, 18, and 29

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29
- Organs examined: in particular urogenital tract

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter
- Head examinations: yes
- other: neonatal survival by placing the pups 24 h in an incubator before tissue examination

Statistics:

no data

Indices:

no data

Historical control data:

no data

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 
13 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 

13 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 

The number of abnormalities seen in either soft or skeletal tissues of the test groups did not
differ from the number occurring spontaneously in the sham-treated controls.

Conclusions:

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 
13 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Executive summary:

A study with Syloid 244 was conducted based on OECD test guideline 414. Rabbits were dosed with 0,  16.0,  74.3,  345 and  1600 mg/kg bw/d.

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 

13 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 

The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The NOAEL was determined to be 1600 mg/kg bw/day.

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Meets generally accepted scientific standards, basic data given, acceptable for assessment, although deficiencies in documentation of test design and results. Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Specific details on test material used for the study:

Syloid 244: CAS-Name: Silica gel, cryst.-free;
CAS-No. 112926-00-8

Species:

hamster, Syrian

Strain:

other: (outbred)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: single
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: water suspension

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No information

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/1
- Length of cohabitation: no data
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

from day 6 to day 10 of gestation

Frequency of treatment:

once daily

Duration of test:

day 14: sacrifice of dams by caesarean section

Remarks:

Doses / Concentrations:
0, 16.0, 74.3, 345 and 1600 mg/kg bw/d
Basis:

No. of animals per sex per dose:

21 - 22 pregnant hamsters

Control animals:

yes, concurrent vehicle

other: pos. control receiving Aspirin, 250 mg/kg bw/*d

Details on study design:

- Dose selection rationale: no data

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 8, 10, and 14


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: no data


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 14
- Organs examined: in particular urogenital tract

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 1/3 per litter
- Head examinations: No data

Statistics:

no data

Indices:

No data

Historical control data:

no data

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
The administration of up to 1600 mg/kg (body weight) of the test material to pregnant hamsters for 
5 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 

Dose descriptor:

NOAEL

Remarks:

(Maximum dose tested)

Effect level:

1 600 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Dose descriptor:

NOAEL

Remarks:

(maximum dose tested)

Effect level:

1 600 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant hamsters for 

5 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. 
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from
the number occurring spontaneously in the sham-treated controls.

Conclusions:

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant hamsters for 
5 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.  The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Executive summary:

A study with Syloid 244 was conducted based on OECD test guideline 414. Rabbits were dosed with 0,  16.0,  74.3,  345 and 1600 mg/kg bw/day.

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant hamsters for 

5 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.  The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The NOAEL was determined to be 1600 mg/kg bw/day.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Details on test material:

Syloid 244: CAS-Name: Silica gel, cryst.-free; CAS-No. 112926-00-8

Specific details on test material used for the study:

Syloid 244: CAS-Name: Silica gel, cryst.-free;
CAS-No. 112926-00-8

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: water suspension

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

No information

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy

Duration of treatment / exposure:

from day 6 to day 15 of gestation

Frequency of treatment:

once daily

Duration of test:

Gestation day 20: sacrifice of all dams by caesarean section

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 13.5, 62.7, 292 and 1350 mg/kg bw/d
Basis:

No. of animals per sex per dose:

20 - 25 pregnant female rats

Control animals:

yes, concurrent vehicle

other: positive control dosed with Aspirin, 250 mg/(kg bw *d)

Details on study design:

- Dose selection rationale: no data

Examinations

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 11, 15, and 20


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: in particular urogenital tract

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: yes

Statistics:

no data

Historical control data:

no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
The administration of up to 1350 mg/kg (body weight) of the test material to pregnant rats for 
10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 350 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 350 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

The administration of up to 1350 mg/kg (body weight) of the test material to pregnant rats for 

10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.
The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ
from the number occurring spontaneously in the sham-treated controls.
   

Applicant's summary and conclusion

Conclusions:

The administration of up to 1350 mg/kg (body weight) of the test material to pregnant rats for 
10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Executive summary:

A study with Syloid 244 was conducted based on OECD test guideline 414. Rats were dosed with 0,  13.5,  62.7,  292 and  1350 mg/kg bw/d.

The administration of up to 1350 mg/kg (body weight) of the test material to pregnant rats for 

10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

The NOAEL was determined to be 1350 mg/kg bw/day