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EC number: 273-761-1 | CAS number: 69012-64-2 Amorphous silicon dioxide particles from the volatilization and vaporization of furnace feed materials in the manufacture of ferrosilicon and silicon.
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Subchronic studies with amorphous silica and a dominant lethal study with calcium silicate have failed to demonstrate any histopathological changes or deleterious effects in the reproductive organs of treated animals. The inherent physico-chemical properties and ubiquitous nature of silicon ion suggest that there is no structural alert to indicate any potential for reproductive toxicity.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No extended one-genereation studies or two-generation studies have been conducted with silica fume or related substances (amorphous silica or silicates). However, the REACH guidelines do not require reproduction toxicity testing if, for example, all of the following circumstances apply: substance exhibits a) low toxicological activity, (b) negligible systemic absorption and (c) no or little significant human exposure. In addition, before any specific reproductive toxicity testing is suggested, a detailed review of all existing toxicological data should be conducted to identify any specific alerts and testing requirements. If this kind of weight-of-evidence analysis shows that there is sufficient data to permit a robust conclusion on reproductive toxicity potential, no further testing is required.
Based on the acute and repeated dose toxicity data on synthetic amorphous silica, silicon ion is virtually non-toxic, showing no systemic toxic effects even at very high oral doses (see Chapter 'Repeated Dose Toxicity'). No harmful effects on reproductive organs have been described in repeated dose toxicity tests. After ingestion, amorphous silica is absorbed from the gastrointestinal tract, but it usually has very little effect on systemic silicon ion levels, that is to say, the levels of silicon in blood, urine or tissues. Silicon in different forms is ubiquitous in nature. Diet is the main factor affecting the blood/urine silicon levels. Diet also causes large inter-individual variability in blood/urine silicon levels. Silicon in different forms is a commonly used food additive and the EFSA (2009) has concluded that adding up to 1,500 mg SiO2/day (equal to 700 mg/day) of silicon dioxide to food supplements is not a safety concern. The OECD (2004) concluded, on the basis of weight-of-evidence, that prolonged exposure to synthetic amorphous silica, applied before and during pregnancy at high doses, is not expected to cause harmful effects to the reproductive performance in experimental animals. This conclusion is based on the information that subchronic studies with amorphous silica and a dominant lethal study with calcium silicate have failed to demonstrate any histopathological changes or deleterious effects in the reproductive organs of treated animals. In addition, the inherent physico-chemical properties and ubiquitous nature of synthetic amorphous silicas suggest that there is no structural alert to indicate any potential for reproductive toxicity.
According to available comparative in vitro dissolution data, the dissolution of silicon from silica fume and synthetic amorphous silica (Aerosil Ox50) is similar, with Aerosil Ox50 showing a somewhat higher release than silica fume. Thus, the bioaccessibility (and bioavailability) of silica fume is likely to be similar or lower than that of synthetic amorphous silica. In circulation, silicon exists in the form of monosilicic acid in both cases.
Thus, the reproductive hazards are likely to be the same, which means that exposure to silica fume is not expected to produce harmful effects on the reproductive performance.
Silica fume may, however, contain impurities whose possible impact on reproductive toxicity should be assessed. According to the CLP/GHS classification criteria for mixtures, any mixture containing a reprotoxicity category 1 or 2 substance of more than 0.3% should be classified as such.
The main impurities present in silica fume at levels over 0.3% and released from it include zinc, magnesium and iron. These are all essential minerals with no reproductive toxic properties and which are also widely used dietary supplements during pregnancy. Lead can affect reproductive toxicity but it is usually present in silica fume only at levels less than 0.3%. Therefore, according to the CLP criteria, its contribution does not need to be considered. Thus, it can be concluded that the known impurities are unlikely to have any impact on silica fume reproductive toxicity and silica fume can be considered to resemble synthetic amorphous silica in this respect.
Effects on developmental toxicity
Description of key information
Animal data on the developmental toxicity of synthetic amorphous silica, calcium silicate and sodium aluminium silicate, which can be used for read-across, do not suggest developmental toxicity or teratogenicity. The inherent physico-chemical properties and ubiquitous nature of silicon ion suggest that there is no structural alert to indicate any potential for developmental toxicity.
Link to relevant study records
- 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
- Qualifier:
- no guideline available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- test material was administered to pregnant animals
- 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
- 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
- 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)
- 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
- Historical control data:
- no data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- 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
- 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
- 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
- Qualifier:
- no guideline available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- test material was administered to pregnant animals
- 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
- 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
- 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
- Historical control data:
- no data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- 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
- 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
- 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
- Qualifier:
- no guideline available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- test material was administered to pregnant animals
- GLP compliance:
- no
- Limit test:
- no
- 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 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:
- 1x/d
- Duration of test:
- day 29: sacrifice of does by Caesarian section
- No. of animals per sex per dose:
- 10, 12, 11, 14, and 13 pregnant animals, respectively (related to dose groups above)
- Control animals:
- yes
- other: pos. control dosed with 6-aminonicotinamide (2.5 mg/kg bw)
- 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
- Historical control data:
- no data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- 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
- 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
- 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
- Qualifier:
- no guideline available
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Principles of method if other than guideline:
- test material was administered to pregnant animals
- GLP compliance:
- no
- Limit test:
- no
- 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
- 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 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
- No. of animals per sex per dose:
- 20 - 25 pregnat 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
- 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: 1/3 per litter
- Head examinations: yes - Statistics:
- no data
- Historical control data:
- no data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- Remarks:
- (highest dose tested)
- Effect level:
- 1 350 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 tested)
- Effect level:
- 1 350 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- (exposure ended 4 days before sacricfice, guideline 1 day)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- hamster
- Strain:
- other: golden hamsters, no other details
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data
- Age at study initiation: adult
- Weight at study initiation: mean weight ca 105 g
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): fresh tap water ad libitum
- Acclimation period: no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: various
- Amount of vehicle (if gavage): 1 ml/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- Gestation days 6 to 10
- Frequency of treatment:
- Daily
- Duration of test:
- 14 days
- No. of animals per sex per dose:
- 22 (positive control: 26)
- Control animals:
- yes, sham-exposed
- 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: Yes (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 14 - 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 early resorptions: No
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter - Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other:
- Remarks on result:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of hamsters to Ca-silicate during days 6-10 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Ca-silicate were studied in hamsters (Food and Drug Research Laboratories 1972). Maternal exposure of rats to Ca-silicate during days 6-10 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- exposure ended 4 days before Caesarian section; guideline 1 day
- GLP compliance:
- no
- Limit test:
- no
- Species:
- hamster
- Strain:
- other: golden hamsters from an outbread strain
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: ca 110 g
- Fasting period before study: no data
- Housing: individually in mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- Days 6 to 10
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- 23 in the control and 1600 mg/kg groups, 24 in the other groups
- Control animals:
- yes, sham-exposed
- Details on study design:
- Positive control: Aspirin 250 mg/kg
- 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 (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 14 - 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 data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: - Statistics:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of hamsters to Na-Al-silicate during days 6-10 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Na-Al-silicate were studied in hamsters (Food and Drug Research Laboratories
1973). Maternal exposure of rats to Na-Al-silicate during days 6-10 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- 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: adult
- Weight at study initiation: 28-32 g
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): fresh tap water ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled temperature
- Humidity (%): controlled humidity
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: various
- Amount of vehicle (if gavage): 1 ml/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy- Duration of treatment / exposure:
- day 6 to day 15 of gestation
- Frequency of treatment:
- daily
- No. of animals per sex per dose:
- 16 mg/kg: 27; 74 mg/kg: 26; 350 mg/kg: 29; 1600 mg/kg: 29 animals
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Other: Positive controls treated with 150 mg/kg Aspirin
- 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 : Yes (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 17 - 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 early resorptions: No
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter - Clinical signs:
- not specified
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Number of abortions:
- no effects observed
- Pre- and post-implantation loss:
- no effects observed
- Total litter losses by resorption:
- no effects observed
- Early or late resorptions:
- no effects observed
- Dead fetuses:
- no effects observed
- Changes in pregnancy duration:
- not specified
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified - Changes in number of pregnant:
- not specified
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Fetal body weight changes:
- no effects observed
- Reduction in number of live offspring:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
- Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Maternal exposure of mice to Ca-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Ca-silicate were studied in mice (Food and Drug Research Laboratories 1972). Maternal exposure of mice to Ca-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- 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: adult
- Weight at study initiation: ca 30 g
- Fasting period before study: no data
- Housing: gang-housed in disposable plastic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, no data
- Humidity (%): controlled, no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details.
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy- Duration of treatment / exposure:
- Day 6 to day 15 of gestation,
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- 32 for the highest dose, 25 for the other doses
- Control animals:
- yes, sham-exposed
- Details on study design:
- Positive control: aspirin 150 mg/kg
- 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 (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 20 - 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 data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter - Statistics:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of mice to Na-Al-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Na-Al-silicate were studied in mice (Food and Drug Research Laboratories 1973). Maternal exposure of mice to Na-Al-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- exposure ended 11 days before Caesarean section: guideline 1 day
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rabbit
- Strain:
- Dutch
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: ca 3.1 kg
- Fasting period before study: no data
- Housing: individually in mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Duration of treatment / exposure:
- Days 6-18 of gestation
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- 16.0 mg/kg: 17 rabbits, 74.3 mg/kg: 15 rabbits, 345.0 mg/kg: 15 rabbits; 1600.0 mg/kg: 23 rabbits. Controls 11 and and positive controls 18/group.
- Control animals:
- yes, sham-exposed
- Details on study design:
- 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, 8, 12, 18 and 29 of gestation
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 29 - 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 data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter - Statistics:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other:
- Remarks on result:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of rabbits to Na-Al-silicate during days 6-18 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Na-Al-silicate were studied in rabbits (Food and Drug Research Laboratories
1973). Maternal exposure of rabbits to Na-Al-silicate during days 6-18 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- (exposure ended 5 days before Caesarean section: guideline 1 day)
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data
- Age at study initiation: adult
- Weight at study initiation: mean weight ca 219 g
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): fresh tap water ad libitum
- Acclimation period: no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Concentration in vehicle: various
- Amount of vehicle (if gavage): 1 ml/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- Days 6 to 15 of gestation
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- Controls: 23, 16 mg/kg: 28; 74 mg/kg: 23; 350 mg/kg: 22; 1600 mg/kg: 25 animals
- Control animals:
- yes, sham-exposed
- Details on study design:
- - Other: Positive controls treated with 250 mg/kg Aspirin
- 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 : Yes (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 20 - 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 early resorptions: No
- Number of late resorptions: Yes
- Other: - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter - Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of rats to Ca-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Ca-silicate were studied in rats (Food and Drug Research Laboratories 1972). Maternal exposure of rats to Ca-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- exposure ended 5 days befor Caesarean section; guideline: 1 day
- GLP compliance:
- no
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: ca 225 g
- Fasting period before study: no data
- Housing: individually in mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, no data
- Humidity (%): controlled, no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- No details
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
- Duration of treatment / exposure:
- Days 6-15 of pregnancy
- Frequency of treatment:
- Daily
- No. of animals per sex per dose:
- 16.0 mg/kg: 28 rats, 74.3 mg/kg: 24 rats, 345.0 mg/kg: 25 rats; 1600.0 mg/kg: 25 rats. Controls and positive controls: 25/group.
- Control animals:
- yes, sham-exposed
- Details on study design:
- Positive control: Aspirin 250 mg/kg.
- 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 (observations, no calculations)
POST-MORTEM EXAMINATIONS: No data
- Sacrifice on gestation day 20 - 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 data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter - Statistics:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- 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
- Effect level:
- 1 600 mg/kg bw/day
- Basis for effect level:
- other: teratogenicity
- Remarks on result:
- other: no effects
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Maternal exposure of rats to Na-Al-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.
- Executive summary:
The teratogenic effects of Na-Al-silicate were studied in rats (Food and Drug Research Laboratories
1973). Maternal exposure of rats to Na-Al-silicate during days 6-15 of pregnancy did not cause any signs of teratogenicity or maternal toxicity even at the highest dose of 1600 mg/kg bw.- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Justification for type of information:
- No toxicological data were available for silica fume and, therefore, a read-across approach was used. The dissolution, composition and surface properties were the most important parameters considered when deciding which substances can be used for read-across.
Based on the composition, surface characteristics, and bioaccessibility data, silica fume was assumed to have toxicological properties similar to those of sparingly synthetic amorphous silicas. Therefore read-across was carried out using available toxicological studies with synthetic amorphous silica (SAS). In addition, data on sparingly soluble silicates was also collected.
Details on the read-across approach are presented in Iuclid section 13. - Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across source
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Basis for effect level:
- other:
- Remarks on result:
- other: No effects observed in any of the studies
- Abnormalities:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other:
- Remarks on result:
- other: No effects observed in any of the studies
- Key result
- Developmental effects observed:
- no
- Conclusions:
- Due to the lack of silica fume studies on developmental toxicity, read-across to other silicon compounds was carried out and the data on synthetic amorphous silica and sparingly soluble silicates were assessed. Teratogenicity test data for several animal species were found for synthetic amorphous silica and silicates. Synthetic amorphous silica, Ca-silicate and Na-Al-silicate did not cause developmental toxicity/teratogenicity in various animal species. Based on read-across, supported by the lack of general systemic effects caused by silicates and silica, there are no indications of potential risks of developmental toxicity that might be caused by silica fume.
Referenceopen allclose all
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.
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 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 ei-
ther soft or skeletal tissues of the test groups did not
differ from the number occurring spontaneously in the sham-
treated controls.
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.
------------
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
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
There is only limited data available on the developmental toxicity of amorphous silica. In these studies, high-dose or long-term oral administration of hydrophilic silica gel did not induce developmental toxicity in several species. However, the teratogenic effects of calcium silicate and sodium aluminium silicate have also been tested in different animal species. All tests showed negative results at high doses. This data supports the conclusion that amorphous silica has no toxic effect on development.
It is also relevant to consider the systemic availability of silica and the level of silicon ion in blood in the evaluation of reproductive toxicity. After ingestion, amorphous silica is absorbed from the gastrointestinal tract but it usually has very little effect on systemic silicon ion levels, that is to say, the levels of silicon in blood, urine or tissues. Silicon in different forms is ubiquitous in nature. Diet is the main factor affecting the blood/urine silicon levels. Diet also causes large inter-individual variability in blood/urine silicon levels. Silicon in different forms is a commonly used food additive and the EFSA (2009) has concluded that adding up to 1,500 mg SiO2/day (equal to 700 mg/day) of silicon dioxide to food supplements is not a safety concern.
The OECD (2004) concluded, on the basis of the weight of evidence, that prolonged exposure to synthetic amorphous silica, applied before and during pregnancy at high doses, is not expected to cause harmful effects to the reproductive performance or embryonic/foetal development in experimental animals. In addition to the fertility studies mentioned earlier, this claim is based on the information that subchronic studies have failed to demonstrate any histopathological changes or deleterious effects in the reproductive organs of treated animals. Furthermore, the inherent physico-chemical properties and ubiquitous nature of synthetic amorphous silicas suggest that there is no structural alert to indicate any potential for reproductive and developmental toxicity.
According to available comparativein vitrodissolution data, the dissolution of silicon from silica fume and synthetic amorphous silica (Aerosil Ox50) is very similar, with Aerosil showing a slightly better release. Thus, the bioaccessibility (and bioavailability) of silica fume is likely to be very similar to synthetic amorphous silica. In circulation, silicon exists in the form of monosilicic acid in both cases. Thus, the reproductive hazards are likely to be the same.
Silica fume may, however, contain impurities whose possible impact on reproductive toxicity should be assessed. According to CLP/GHS classification criteria for mixtures, any mixture containing a reprotoxicity category 1 or 2 substance of more than 0.3% should be classified as such.
The main impurities present in silica fume at levels over 0.3% and released from it include zinc, magnesium and iron. These are all essential minerals with no reproductive toxic properties and which are also widely used dietary supplements during pregnancy. Lead can affect reproductive toxicity but it is usually present in silica fume only at levels of less than 0.3%. Therefore, according to the CLP criteria, its contribution does not need to be considered. Thus, it can be concluded that the known impurities are unlikely to have any impact on silica fume reproductive toxicity and silica fume can be considered to resemble synthetic amorphous silica in this respect.
Justification for classification or non-classification
Subchronic studies with amorphous silica and a dominant lethal study with calcium silicate have failed to demonstrate any histopathological changes or deleterious effects in the reproductive organs of treated animals. The inherent physico-chemical properties and ubiquitous nature of silicon ion suggest that there is no structural alert to indicate any potential for reproductive toxicity.
Animal data on the reproductive toxicity of synthetic amorphous silica, calcium silicate and sodium aluminium silicate which can be used for read-across, do not suggest developmental toxic effects. The inherent physico-chemical properties and ubiquitous nature of silicon ion suggest that there is no structural alert to indicate any potential for reproductive and developmental toxicity.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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