Cordierite (Mg2[Al4O3(SiO3)5])

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

Study period:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was conducted using a method similar to OECD Testing Guideline 414 and meets acceptable scientific standards.

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:

yes

Remarks:

The highest dose tested is above the limit dose recommended.

GLP compliance:

no

Limit test:

yes

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:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): FDA 71-45 (Sodium silicoaluminate)
- Physical state: Fine white powdered material

Test animals

Species:

rabbit

Strain:

Dutch

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: not provided
- Age at study initiation: not provided (adult)
- Weight at study initiation: not provided
- Fasting period before study: not provided
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, no details provided
- Humidity (%): controlled, no details provided
- Air changes (per hr): not provided
- Photoperiod (hrs dark / hrs light): not provided

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): not provided
- Mixing appropriate amounts with (Type of food): not provided
- Storage temperature of food: not provided

VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: 125 - 250 mg/ml
- Amount of vehicle (if gavage): 1, 2, 3, 4, 5, 6, 6.4 ml/kg bw

Analytical verification of doses or concentrations:

no

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: not provided
- Length of cohabitation: not provided
- Further matings after two unsuccessful attempts: not provided
- Verification of same strain and source of both sexes: not provided

Duration of treatment / exposure:

Beginning on Day 6 through Day 18 of gestation

Frequency of treatment:

Daily

Duration of test:

Termination on Day 29 of gestation

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 16, 74.3, 345 and 1600 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

10 - 16 animals per dose

Control animals:

yes, concurrent vehicle

other: positive control: 2.5 mg/kg of 6-aminonicotinamide

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

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

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

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29
- Organs examined: detailed examination of the 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: all per litter

The live fetuses of each litter were then placed in an incubator for 24 hours for the evaluation of neonatal survival.

Statistics:

Not provided

Indices:

Not provided

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 evaluated

Effect level:

1 600 mg/kg bw/day

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 evaluated

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 1600.0 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.

Applicant's summary and conclusion

Conclusions:

The NOAEL (maternal toxicity) and NOAEL (teratogenicity) are above 1600 mg/kg, which is the highest concentration evaluated during this study.

Executive summary:

The prenatal developmental toxicity of the read-across substance sodium silicoaluminate branded as FDA 71-45 was determined according to a method similar to the OECD Guideline for Testing of chemicals 414. The teratogenicity of the substance dispersed in water was studied in rabbits during days 6 to 18 of pregnancy. Body weights were recorded on Days 0, 6, 12, 18, and 29 of gestation. All animals were observed daily for appearance and behavior with particular attention to food consumption and weight, in order to rule out any abnormalities which may have occurred as a result of anorexic effects in the pregnant female animals.

On Day 29 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of corpora lutea, implantation sites, resorption sites and live and dead fetuses were recorded. Body weights of the live pups were also recorded. The urogenital tract of each animal was examined in detail for normality. In addition all fetuses underwent a detailed gross examination for the presence of external congenital abnormalities. The live fetuses of each litter were then placed in an incubator for 24 hours for the evaluation of neonatal survival. All surviving pups were sacrificed, and all pups examined for visceral abnormalities (by dissection). All fetuses were then cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

The administration of up to 1600.0 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 (maternal toxicity) and NOAEL (teratogenicity) are above 1600 mg/kg, which is the highest concentration evaluation during this study.