Synthetic wollastonite

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): used as dispersant
- Concentration in vehicle: depending on the dose
- Amount of vehicle (if gavage): 1 mL suspension/kg bw (Tab. 1, p. 2)
[note: not conclusive, is supposed to read 10 mL/kg b.w., comp. corresponding report on NAS]

Analytical verification of doses or concentrations:

no

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:

1x/d

Duration of test:

gestation day 17: sacrifice of all dams by Caesarian section

Remarks:

Doses / Concentrations:
0, 16, 74, 350 and 1600 mg/(kg*d) (as aqueous suspension)
Basis:

No. of animals per sex per dose:

20 - 23 pregnant dams

Control animals:

yes, sham-exposed

other: positive control dosed with Aspirin [150 mg/(kg bw*d)]

Details on study design:

- Other: Sham control is said to be dosed with corn oil, see Tab. 1, p. 2
(probably erroneous, contradicting corresponding report on NAS)

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 11, 15, and 17 (Tab. 4, p. 6)


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (not documented)
- 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: Yes (neonatal pup weight) [Appendix II, p. 8]
- 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

Details on maternal toxic effects:

Maternal toxic effects:no effects

Key result

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

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 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 1600 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.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): used as dispersant
- Concentration in vehicle: depending on the dose
- Amount of vehicle (if gavage): 1 mL suspension/kg bw (Tab. 1, p. 28)
[note: not conclusive, is supposed to read 10 mL/kg b.w., comp. corresponding report on NAS]

Analytical verification of doses or concentrations:

no

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:

1x/d

Duration of test:

day 14: sacrifice of dams by Caesarian section

Remarks:

Doses / Concentrations:
0, 16.0, 74, 345 and 1600 mg/(kg bw*d)
Basis:

No. of animals per sex per dose:

19 - 22 pregnant hamsters

Control animals:

yes, sham-exposed

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

Details on study design:

- Other: Sham control is said to be dosed with corn oil, see Tab. 1, p. 28
(probably erroneous, contradicting corresponding report on NAS)

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: yes (neonatal pup weight) [Appendix II, p. 34]
- 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: No data

Statistics:

no data

Historical control data:

no data

Details on maternal toxic effects:

Maternal toxic effects:no effects

Key result

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Key result

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 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 occuring 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 occuring spontaneously in the sham-treated controls.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1972

Report date:

1972

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:

Silicic acid, calcium salt

EC Number:

215-710-8

EC Name:

Silicic acid, calcium salt

Cas Number:

1344-95-2

IUPAC Name:

calcium oxosilanediolate

Details on test material:

- Name of test material: FDA-Compound 71-41
- Trade name: Silene EF (calcium silicate, hydrated)
- Substance type: inorganic
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: water suspension

VEHICLE
- Justification for use and choice of vehicle (if other than water): used as dispersant
- Concentration in vehicle: depending on the dose
- Amount of vehicle (if gavage): 1 mL suspension/kg bw (Tab. 1, p. 15)
[note: not conclusive, is supposed to read 10 mL/kg b.w., comp. corresponding report on NAS]

Analytical verification of doses or concentrations:

no

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:

1x/d

Duration of test:

Gestation day 20: sacrifice of all dams by Caesarian section

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 16, 74, 350 and 1600 mg/(kg*d) (as aqueous suspension)
Basis:

No. of animals per sex per dose:

20 - 22 pregnant female rats

Control animals:

yes, sham-exposed

other: positve control dosed with Aspirin (250 mg/kg bw)

Details on study design:

- Dose selection rationale: no data
- Other: Sham control is said to be dosed with corn oil, see Tab. 1, p. 15
(probably erroneous, contradicting corresponding report on NAS)

Examinations

Maternal examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 11, 15, and 20 (Tab. 4, p. 19)


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (not documented)
- 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 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: Yes (neonatal pup weight) [Appendix II, p. 21]
- 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

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 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 1600 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 1600 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.