Silicic acid, aluminum calcium sodium salt

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

21 May - 07 June 1979

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Screening study/limited examination: meets generally accepted scientific standards, sufficiently documented, database insufficient for complete assessment. No study guideline provided. 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Method: screening/range-finding for 90-d study: Reduced number of animals; no comprehensive examinations in haematology/clinical chemistry/urinalysis/limited histopathology (only high-dose and control group: 3 animals each).

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid, aluminum sodium salt

EC Number:

215-684-8

EC Name:

Silicic acid, aluminum sodium salt

Cas Number:

1344-00-9

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Sodium Aluminosilicate
- Substance type: inorganic
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Lot/batch No.: B71778

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

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 indivual data available / mean weights 179 - 184 g (male); 153 - 156 g (female)
- Fasting period before study: none
- Housing: 5/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 17 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +-1 (Report 74 +-2 °F)
- Humidity (%): 50 +-5
- Air changes (per hr): 10 - 15x
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): 1x/week
- Mixing appropriate amounts with (Type of food): NIH-07 Rat and Mouse Ration Mash

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

14 d

Frequency of treatment:

continuous

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0.625%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
1.25%
Basis:
nominal in diet

Doses / concentrations 3

Remarks:

Doses / Concentrations:
2.5%
Basis:
nominal in diet

Doses / concentrations 4

Remarks:

Doses / Concentrations:
5%
Basis:
nominal in diet

Doses / concentrations 5

Remarks:

Doses / Concentrations:
10%
Basis:
nominal in diet

No. of animals per sex per dose:

5

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: 1 d (day 15)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: day 0, 7, and 14


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Mean weekly food consumption of each group is given after week 1 and 2 (Tab. 4)
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


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


OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, on 10% of the animals (6/60), 2 female and 1 male each from the control and the 10% group

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Male rats of the highest-dosed group showed a significantly lower bw gain (-39 %), which may be considered to be treatment-related.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

BODY WEIGHT AND WEIGHT GAIN:  
Male rats of the highest-dosed group showed a significantly lower body weight gain (-39%), which may be considered to be treatment-related.

Effect levels

1

Dose descriptor:

NOAEL

Remarks:

5% dietary level

Effect level:

ca. 4 750 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: body weight

2

Dose descriptor:

NOAEL

Remarks:

10% dietary level

Effect level:

ca. 7 000 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL (5% dietary level) was 4750 mg/kg bw/day in male rats (based on body weight). Male rats in the highest-dosed group showed a significantly lower body weight gain (-39%), which may be considered to be treatment-related. The NOAEL (10% dietary level) was 7000 mg/kg bw/day in female rats (based on overall effects). No clinical signs or mortality was recorded. There were no effects reported during gross pathology or histopathological investigation.

Executive summary:

The repeated dose toxicity of the test substance was determined, with no test guideline provided. The method followed involved a screening/range-finding test for 90-day study. The method used a reduced number of animals; there were no comprehensive examinations in haematology/clinical chemistry/urinalysis/limited histopathology (only high-dose and control group: 3 animals each). The study investigated the toxicity of repeated oral exposure of the test substance to male and female rats. Animals were exposed to 0.625 -10% doses, as part of the diet, for 14 days. The NOAEL (5% dietary level) was 4750 mg/kg bw/day in male rats (based on body weight). Male rats in the highest-dosed group showed a significantly lower body weight gain (-39%), which may be considered to be treatment-related. The NOAEL (10% dietary level) was 7000 mg/kg bw/day in female rats (based on overall effects). No clinical signs or mortality was recorded. There were no effects reported during gross pathology or histopathological investigation. The test susbtance is not considered to be toxic to rats via repeated oral exposure. 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.