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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

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

Referenceopen allclose all

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

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.

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

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.
   -----------

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

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.

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

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.
   ------------

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.
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