Cordierite (Mg2[Al4O3(SiO3)5])

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because (i) the substance is of low toxicological activity (no evidence of toxicity seen in any of the tests available), (ii) it can be proven from toxicokinetic data that no systemic absorption occurs via relevant routes of exposure (e.g. plasma/blood concentrations below detection limit using a sensitive method and absence of the substance and of metabolites of the substance in urine, bile or exhaled air) and (iii) there is no or no significant human exposure

Justification for type of information:

In accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance (Version 4.0), the study does not need to be performed as no statically significant effects on reproductive organs and tissues nor concerns in relation with reproductive toxicity were identified on the substance and its analogues during the repeated dose toxicity studies nor the prenatal developmental toxicity studies. Moreover, in accordance with Annex IX of REACH, Column 2, taking into account the toxicokinetics profile of the substance, the systemic absorption following exposure by oral route is considered to be inconsequential.

Reproductive effects observed:

not specified

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Additional information

In accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance (Version 4.0), the study does not need to be performed as no statically significant effects on reproductive organs and tissues nor concerns in relation with reproductive toxicity were identified on the substance and its analogues during the repeated dose toxicity studies nor the prenatal developmental toxicity studies.

Moreover, in accordance with Annex IX of REACH, Column 2, taking into account the toxicokinetics profile of the substance, the systemic absorption following exposure by oral route is considered to be inconsequential.

Justification for selection of Effect on fertility via oral route:

In accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance (Version 4.0), the study does not need to be performed as no statically significant effects on reproductive organs and tissues nor concerns in relation with reproductive toxicity were identified on the substance and its analogues during the repeated dose toxicity studies nor the prenatal developmental toxicity studies.

Moreover, in accordance with Annex IX of REACH, Column 2, taking into account the toxicokinetics profile of the substance, the systemic absorption following exposure by oral route is considered to be inconsequential.

Effects on developmental toxicity

Description of key information

The developmental toxicity/teratogenicity study by oral route was conducted on a read-across substance according to a method similar to OECD Testing Guideline 414 on four different species. The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 13 consecutive days, to pregnant rats for 10 consecutive days, to pregnant hamsters for 5 consecutive days, and 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 (maternal toxicity) and NOAEL (teratogenicity) are above 1600 mg/kg, which is the highest concentration evaluated during these studies. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Link to relevant study records

Reference

Reference 1

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.

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

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

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

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

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

Details on maternal toxic effects:

Maternal toxic effects:no effects

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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 1600.0 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.

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.

Reference 2

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

supporting 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.

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. Number of corpora lutea was not provided.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Wistar

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

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 15 of gestation

Frequency of treatment:

Daily

Duration of test:

Termination on Day 20 of gestation

Remarks:

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

No. of animals per sex per dose:

21 - 23 animals per dose

Control animals:

yes, concurrent vehicle

other: positive control: Aspirin 250 mg/kg bw

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 11, 15, and 20 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 20
- 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: No
- Number of implantations: Yes
- Number of early 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: all per litter

Statistics:

Not provided

Historical control data:

Not provided

Details on maternal toxic effects:

Maternal toxic effects:no effects

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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 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.

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 rats during days 6 to 15 of pregnancy. Body weights were recorded on Days 0, 6, 11, 15, and 20 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 20 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation sites, resorption sites, and live and dead fetuses were recorded. The body weight of the live pups were also recorded. The arogenital tract of each dam was examined in detail for anatomical normality. All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing 10x magnification. The remaining two-thirds were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

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

Reference 3

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

supporting 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.

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. Study was performed on a non-standard species (hamster). Number of corpora lutea was not provided.

GLP compliance:

no

Limit test:

yes

Species:

hamster

Strain:

other: golden hamsters

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

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 10 of gestation

Frequency of treatment:

Daily

Duration of test:

Termination on Day 14 of gestation

Remarks:

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

No. of animals per sex per dose:

22 animals per dose

Control animals:

yes, concurrent vehicle

other: positive control: Aspirin 250 mg/kg bw

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 8, 10, and 14 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 14
- Organs examined: detailed examination of the genital 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: No
- 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: all per litter

Statistics:

Not provided

Indices:

Not provided

Historical control data:

Not provided

Details on maternal toxic effects:

Maternal toxic effects:no effects

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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 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 hamsters during days 6 to 10 of pregnancy. Body weights were recorded on Days 0, 8, 10, and 14 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 14 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation sites, resorption sites, and live and dead fetuses were recorded. The body weight of the live pups were also recorded. The genital tract of each dam was examined in detail for anatomical normality. All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing 10x magnification. The remaining two-thirds were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

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

Reference 4

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

supporting 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.

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. Study was performed on a non-standard species (mouse). Number of corpora lutea was not provided.

GLP compliance:

no

Limit test:

yes

Species:

mouse

Strain:

CD-1

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

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 15 of gestation

Frequency of treatment:

Daily

Duration of test:

Termination on Day 17 of gestation

Remarks:

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

No. of animals per sex per dose:

19 - 24 animals per dose

Control animals:

yes

other: positive control: Aspirin 150 mg/kg bw

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 11, 15, and 17 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 17
- 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: No
- 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: all per litter

Statistics:

Not provided

Indices:

Not provided

Historical control data:

Not provided

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

Effect level:

1 600 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Dose descriptor:

NOAEL

Remarks:

highest dose evaluated

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 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 mice during days 6 to 15 of pregnancy. Body weights were recorded on Days 0, 6, 11, 15, and 17 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 17 all dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation sites, resorption sites, and live ·and dead fetuses were recorded. The body weights of the live pups were also recorded. The urogenital tract of each dam was examined in detail for anatomical normality. All fetuses were examined grossly for the presence of external congenital abnormalities. One-third of the fetuses of each litter underwent detailed visceral examinations employing 10x magnification. The remaining two-thirds were cleared in potassium hydroxide (KOB), stained with alizarin red S dye and examined for skeletal defects.

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.

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

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 600 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Quality of whole database:

The study was considered as reliable as it was performed on a read-across substance according to a method similar to OECD Testing Guideline 414 on rabbits - which is the recommended non-rodent species for this study - and meets acceptable scientific standards. Only deviation from the current OECD Testing Guideline is the highest dose evaluated (1600 mg/kg bw) being above the limit concentration recommended in the Guideline (1000 mg/kg bw).

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

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, in rats during days 6 to 15 of pregnancy, in hamsters during days 6 to 10 of pregnancy, and in mice during days 6 to 15 of pregnancy. Body weights were recorded on a regular basis during 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.

All dams were subjected to Caesarean section under surgical anesthesia, and the numbers of implantation sites, resorption sites and live and dead fetuses were recorded, along with the number of corpora lutea for rabbits. 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 gross examination for the presence of external congenital abnormalities. All surviving pups were sacrificed. All rabbit pups were examined for visceral abnormalities (by dissection) then cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects. One-third of the fetuses of each rat, mouse, and hamster litter underwent detailed visceral examinations employing 10x magnification; the remaining two-thirds were cleared in potassium hydroxide (KOH), stained with alizarin red S dye and examined for skeletal defects.

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rabbits for 13 consecutive days, to pregnant rats for 10 consecutive days, to pregnant hamsters for 5 consecutive days, and 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 (maternal toxicity) and NOAEL (teratogenicity) are above 1600 mg/kg, which is the highest concentration evaluated during these studies. The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.

Justification for selection of Effect on developmental toxicity: via oral route:

The study was performed on a read-across substance according to a method similar to OECD Testing Guideline 414 on rabbits, which is the recommended non-rodent species for this study.

Justification for classification or non-classification

The NOAEL (maternal toxicity) and NOAEL (teratogenicity) of the read-across substance are above 1600 mg/kg, which is the highest concentration evaluated during the developmental toxicity / teratogenicity studies. In accordance with the Guidance on Information Requirements and Chemical Safety Assessment Chapter R.7a: Endpoint specific guidance (Version 4.0), it was not considered scientifically justified to evaluate the effects of the registered substance on fertility.

The test item did not meet the criteria for classification according to Regulation (EC) No.1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures.