Silicic acid, aluminum calcium sodium salt

Endpoint summary

Description of key information

The substance is not considered acutely toxic via the oral, inhalation or dermal routes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted by GLP compliant laboratory using OECD Testing Guideline 401.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Species:

mouse

Strain:

other: ddY-N

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Exposure period of 14 days

Doses:

1160, 1380, 1660 and 2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: The excretion of the soft and caddy stool movement and pollution of the cover hair were observed in 1-3 cases after the dosage, but, as for the constant tendency, it was admitted that male and female in the degree of the outbreak situation and the symptom

Gross pathology:

As a result of killing all mice at the time of the examination end, and having held an autopsy by eye, the abnormality was not accepted by a main organ.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral lethal dose (LD50) of the test material in mice was found to be >2000 mg/kg bodyweight.

Executive summary:

The acute oral toxicity of the substance was determined in accordance with the OECD Guideline for Testing of Chemicals 401. The acute oral lethal dose (LD₅₀) of the test material in mouse was found to be >2000 mg/kg bodyweight. The substance is therefore not classified as an acute oral toxin according to EU CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The acute oral lethal dose (LD50) of the test material in mouse was found to be >2000 mg/kg bodyweight. The substance is therefore not classified as an acute oral toxin according to EU CLP criteria.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was conducted at the request of CEFIC-ASASP, Brussels, and followed adapted OECD Testing Guidelines for acute, subacute and subchronic inhalation toxicity. The study is included in the peer reviewed Food and Chemical Toxicology Journal. Read-across from the results on the test substance has been made to the registered substance based on the similar structure of the two substances.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline available

Principles of method if other than guideline:

The study was conducted in order to compare results with those of 90-day, subchronic inhalation studies. The study was designed to provide evidence that short-term (five-day) exposure can provide comparable prediction of toxicity to those of 90-day studies. There are no references made to specific testing guidelines in the report (with the exception of the animal procedures which were carried out according to OECD 412, and GLP guidelines). The study appears to utilise adapted versions of OECD 412 and 413, based on a comparison of the published study and the relevant OECD test guidelines.

GLP compliance:

not specified

Remarks:

There is no specific mention of GLP compliance (with the exception of the animal procedures which were carried out according to GLP).

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Young adult, Wistar (Crl:(WI)WU BR) rats were purchased from Charles River Deutschland (Sulzfeld, Germany). The animals were acclimatised for at least 5 days before the start of the study. They were kept under conventional laboratory conditions in suspended, stainless steel cages fitted with wire mesh floor and front, two, three or five rats per cage and received powdered RM3 rodent diet and unfluoridated tap water ad libitum. The animal rooms were ventilated with about 10 air changes per hour and were maintained at a temperature of 22°C ± 2°C and a relative humidity of at least 30% and not exceeding 70% other than during room cleaning. All animal procedures were approved by the TNO Committee on Animal Welfare and carried out according to OECD 412 and OECD GLP guidelines.

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Remarks:

Filtered, ambient air

Details on inhalation exposure:

Electromagnetically driven, miniature dust feeders (Institute's design) were used that released periodically (with periods in the range of 2-8 or 6-12 s) small lumps of test material to low velocity eductors in which the test material were aerosolised. Separate aerosol generators were used for each unit. All test materials were delivered using a slip stream of filtered ambient air. The eductors were operated with compressed humidified air, using mass flow controllers. At the entrance of each exposure unit, the generated aerosol was diluted with measured amounts of humidified air.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The concentration of the test material in the test atmosphere was determined by gravimetric analysis. The actual concentrations were calculated by dividing the amount of test material present on each fibre glass filter by the volume of the sample taken.

Duration of exposure:

5 d

Concentrations:

1, 5 and 25 mg/m^3

No. of animals per sex per dose:

10 male rats

Control animals:

yes

Details on study design:

Only male rats were used in this study because of a slightly higher sensitivity in male rats when compared to female rats in initial experiments with a similar substance (see 'Acute toxicity: inhalation_read-across_precipitated silica'). The exposure groups consisted of 10 males each, the control groups II consisted of 12 males each. Positive controls were exposed to 25 mg/m^3 crystalline silica (quartz dust), negative controls were exposed to clean air.

During exposure, the rats were individually restrained in Battelle tubes and each tube was then placed into one of the inhallation units for head/nose-only exposure to the test atmosphere. Each unit had a volume of approximately 50 l, with an exposure air flow of 51 l/min. Daily mean temperature of the test atmospheres was between 21.9°C and 25.5°C with standard deviations between 0.1°C to 1.2°C; daily mean relative humidity was between 29% and 51% with standard deviations of 1-2%. Rats were exposed for 6h/day for five consecutive days.

Statistics:

Body weight data were analysed by one-way analysis of co-variance (ANCOVA) using pre-exposure (day 0) weights as the covariate. Total cell counts, absolute differential cell counts and biochemical parameters in (bronchoalveolar lavage fluid) BALf, silicon content in the lungs and lymph nodes, and weights of these organs were analysed by one-way analysis of variance (ANOVA).

Sex:

male

Dose descriptor:

other: NOAEL

Effect level:

1 mg/m³ air

Based on:

test mat.

Exp. duration:

5 d

Remarks on result:

other: No serious treatment-related changes were observed in animals of the low exposure group directly after exposure. The level of 1 mg/m^3 was therefore considered a NOAEL for this substance.

Mortality:

No treatment-related mortality was observed during the study period.

Clinical signs:

other: No treatment-related clinical signs were observed during the study period.

Body weight:

No changes in body weight gain were observed in any of the dose groups.

Gross pathology:

There were no treatment-related gross lesions at necropsy.

Other findings:

Microscopic examination revealed substance-related changes in the lungs and tracheobronchial lymph nodes. Most histopathological changes were observed at 25 mg/m^3, and to a lesser degree at 5 mg/m^3, and none at 1 mg/m^3. Directly after the exposure period, the histopathological changes in the lungs that were observed consisted of increased intra-alveolar accumulation of macrophages and bronchial/bronchiolar hypertrophy. All of the noted changes were very slight to slight. No changes were observed in the tracheobronchial lymph nodes.

Of the three SAS substances which were tested (see the additional study records for this endpoint) silica gel induced the least pronounced changes in markers of lung inflammation, but with a slight increase in hydroxyproline content three months after the last exposure. These results are similar to those of other studies that had 90 -day exposure periods e.g. Reuzel et al. (1991). SAS induced changes were generally most apparent the day after the last exposure and disappeared relatively fast within three months post-exposure. In contrast, the quartz (i.e. the positive control) induced pulmonary changes were minimal at the end of the five day exposure period but progressed clearly thereafter with slight changes one month post-exposure and overt changes three months after the last exposure. Clearance of the silica gel from the lungs during the post-exposure period was rapid as amounts of silicon were mostly below the detection limit one month after exposure. In contrast, quartz dust was not cleared at all during the three month post-exposure period. It appeared that the vast majority of the silica gel was dissolved rapidly in the lung fluid and removed via the mucocilliary escalator within three months post-exposure.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study gave a NOAEL of 1 mg/m^3 for silica gel. No treatment-related deaths or clinical signs were observed during the study, therefore the substance is not classified as an acute inhaltion toxin according to EU CLP criteria.

Executive summary:

The acute inhalation toxicity of the test substance was determined in accordance with adapated OECD Guidelines for Testing of Chemicals (possibly 412 and 413 based on the method information provided). Male Wistar rats were exposed nose-only to concentrations of 1, 5 and 25 mg/m³ of silica gel 6 hours per day for five consecutive days. Positive controls were exposed to 25 mg/m³ of crystalline silica (quartz dust), negative controls were exposed to clean air. Animals were necropsied the day after the last exposure, or one or three months later. All exposures were tolerated without serious clinical effects, changes in body weight or food intake. Silicon was found in the lungs one day after exposure to 25 mg/m³ of silica gel but was cleared three months later. Some effects were seen in the lungs at the highest exposure concentration, however, these effects were transient and reversible during the three month recovery period. No adverse reactions were seen at the 1 mg/m³ exposure level, therefore 1 mg/m3 was assigned as the NOAEL for this substance. The substance is not classified as an acute inhaltion toxin according to EU CLP criteria.

The structure of both silica gel (silicon dioxide) and silicic acid, aluminium, calcium, sodium salt are macromolecular skeletons of silicon and oxygen. In the silicic acid, aluminium, calcium, sodium salt the metal cations bind ionically to negatively charged oxygens in the structure. The inclusion of the metal cations to the structure of silica gel (silcon dioxide) would not change the toxicity of the substance, or the behaviour of the substance once inhaled.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The NOAEL of the test substances (silica gel, pyrogenic silica and precipitated silica) was found to be 1 mg/m^3. The substance is not classified as an acute inhalation toxin according to EU CLP criteria.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was conducted using a test method similar to OECD Testing Guideline 402, with one amendment. Limited documentation is available, the study is considered acceptable for assessment. Read-across from the results on the test substance has been made to the registered substance based on the similar structure of the two substances.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

24 hour exposure, abraded and intact skin

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

The test substance was applied as paste to the intact and abraded skin of 2 animals of each dose group
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: impervious bandage
- The test substance was applied as paste to the intact and abraded skin of 2 animals each of the dose group

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- For solids, paste formed: yes, aqueous

VEHICLE
- Amount(s) applied (volume or weight with unit): no data

Duration of exposure:

24 h

Doses:

2000, 3000, 4000, and 5000 mg/kg as aqueous paste

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Dose descriptor:

LD0

Effect level:

>= 5 000 mg/kg bw

Mortality:

none: 0/16 (0/4 per each dose group)

Clinical signs:

other: no data

Gross pathology:

No pathological findings

Other findings:

Dermal reactions were limited to slight erythema and edema.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance was found to be >5000 mg/kg bw. The substance is not classified as an acute dermal toxin according to EU CLP criteria.

Executive summary:

The acute dermal toxicity of the test substance was determined via use of a guideline similar to the OECD Guideline for Testing of Chemicals 402, with the ammendment from OECD 402 being 24 hour exposure to abraded and intact skin. The test involved occlusive application of between 2000 and 5000 mg/kg bw of the test substance to the abraded and intact skin of rabbits. No mortality was recorded and the LD50 was reported as >5000 mg/kg bw. The substance is not classified as an acute dermal toxin accoring to EU CLP criteria. The structure of both silicic acid, aluminium, sodium salt and silicic acid, aluminium, calcium, sodium salt are macromolecular skeletons of silicon and oxygen with the metal cations binding ionically to negatively charged oxygens in the structure. In the silicic acid, aluminium, calcium, sodium salt the metal cations bind ionically to negatively charged oxygens in the structure. The inclusion of calcium salts to the structure of silicic acid, aluminium, sodium salt would not be expected to change the toxicity of the substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The LD50 of the test substance was found to be >5000 mg/kg bw. The substance is not classified as an acute dermal toxin according to EU CLP criteria.

Additional information

A study was conducted on the registered substance to determine the acute oral toxicity of the substance. The acute oral lethal dose (LD₅₀) of the test material in mouse was found to be >2000 mg/kg bodyweight. The substance is therefore not classified as an acute oral toxin according to EU CLP criteria.

A read-across was made from a study conducted on the similar substance silicic acid, aluminium, sodium salt to the registered substance to determine the acute dermal toxicity of the substance. The acute dermal LD₅₀ of the test substance was found to be >5000 mg/kg bw. The registered substance is not classified as an acute dermal toxin according to EU CLP criteria.

A study was conducted on three substances (silica gel, precipitated silica and pyrogenic silica) with similar structures to the registered substance. The NOAEL was found to be 1 mg/m³. The registered substance is not classified as an acute inhalation toxin according to EU CLP criteria.

Justification for selection of acute toxicity – oral endpoint
This study was conducted on the registered substance according to GLP standards and using OECD Testing Guideline 401.

Justification for selection of acute toxicity – inhalation endpoint
This study was conducted on a substance which is structurally similar to the registered substance using acceptable testing methods and published in a peer reviewed journal.

Justification for selection of acute toxicity – dermal endpoint
This study was conducted on a substance which is structurally similar to the registered substance using OECD Testing Guideline 402.

Justification for classification or non-classification

The acute oral lethal dose (LD₅₀) of the test material in mouse was found to be >2000 mg/kg bodyweight. The substance is therefore not classified as an acute oral toxin according to EU CLP criteria.

The acute dermal LD₅₀of a substance with structural similarity to the registered substance was found to be >5000 mg/kg bw. The results of testing on the similar substance were read across to the registered substance. The registered substance is therefore not classified as an acute dermal toxin according to EU CLP criteria.

The acute inhalation toxicity NOAEL was found to be 1 mg/m³. The registered substance is not classified as an acute inhalation toxin according to EU CLP criteria