Silicic acid, aluminum calcium sodium salt

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was conducted using OECD Testing Guideline 414 and meets generally accepted scientific standards. Basic data given (e.g. results tables are provided), considered acceptable for assessment. Read-across from the results on the test substance has been made to the registered substance based on the similar structure of the two substances.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

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)

Deviations:

not specified

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid, aluminum sodium salt

EC Number:

215-684-8

EC Name:

Silicic acid, aluminum sodium salt

Cas Number:

1344-00-9

Test material form:

not specified

Details on test material:

FDA-Compound 71-45 ("sodium silicoaluminate")

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

VEHICLE
- Justification for use and choice of vehicle (if other than water): used as dispersant
- Concentration in vehicle: maximum 1500-1600 mg NAS/6.4 ml water => 10 ml suspension/kg bw
- Amount of vehicle (if gavage): adjusted to the dose, from 1 ml water/kg bw to 6.4 ml water/kg bw

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:

Once per day

Duration of test:

Gestation day 20: sacrifice of all dams by Caesarian section

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw/day (as aqueous suspension)
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
16 mg/kg bw/day (as aqueous suspension)
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
74 mg/kg bw/day (as aqueous suspension)
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
350 mg/kg bw/day (as aqueous suspension)
Basis:
nominal conc.

Doses / concentrations 5

Remarks:

Doses / Concentrations:
1600 mg/kg bw/day (as aqueous suspension)
Basis:
nominal conc.

No. of animals per sex per dose:

21 - 23 pregnant female rats

Control animals:

yes, concurrent vehicle

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

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 (not documented)
- 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: Yes (neonatal pup weight)
- 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)

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Based on:

no data

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Remarks:

(highest dose tested)

Effect level:

1 600 mg/kg bw/day

Based on:

no data

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 NOAEL for both maternal toxicity and teratogenicity was 1600 mg/kg bw/day i.e. no dose related effects were seen at the maximum dose used in the test. 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.

Executive summary:

The developmental toxicity and teratogenicity of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 414. Doses of 0 - 1600 mg/kg bw/day were administered to pregnant female rats for 10 consecutive days via oral (gavage) exposure. The NOAEL for both maternal toxicity and teratogenicity was 1600 mg/kg bw/day i.e. no dose related effects were seen at the maximum dose used in the test. 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. The substance is not considered to cause developmental or teratogenic effects in rats. The structure of both silicic acid,

aluminium, sodium salt and silicic acid, aluminium, calcium, sodium salt are macromolecular skeletons of silicon and oxygen with the metal cations binding ionically to negatively charged oxygens in the structure. In the silicic acid, aluminium, calcium, sodium salt the metal cations bind ionically to negatively charged oxygens in the structure. The inclusion of calcium salts to the structure of silicic acid, aluminium, sodium salt would not be expected to change the toxicity of the substance.