Registration Dossier

Administrative data

Description of key information

NOAEL (rats) = 159 mg/kg bw/day 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented study, but test substance not clearly identified and background exposure through diet not stated.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
no
Species:
rat
Strain:
other: Charles River Cesarean-Derived (CD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS
- Weight at study initiation:  80-100 g
Route of administration:
oral: feed
Vehicle:
other: feed
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
2400 mg/kg bw/d
Basis:
other: nominal conc.
No. of animals per sex per dose:
15
Control animals:
yes
Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY: 
- Clinical signs: registered daily
- Mortality: registered daily
- Body weight: registered weekly
- Food consumption: registered with unknown frequency
- Haematology: Total WBC count, differential WBC count, packed cell volume, prothrombine time and serum hemoglobin was registered weekly. 
- Urinalysis: Urinary specific gravity protein concentration, glucose concentration and urea nitrogen was registered weekly.
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): 
- Macroscopic: the weight of not specified organs was registered.
- Microscopic: A set of tissues was preserved in formalin for histopathological examination. There are no further details.
Dose descriptor:
NOAEL
Effect level:
2 400 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: polydipsia, polyuria and soft stools
Critical effects observed:
not specified

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: None
- Clinical signs: Polydipsia, polyuria and soft stools was observed in a few animals (not quantified)
- Body weight gain: No effects
- Food/water consumption: No effects
- Clinical chemistry: No effects
- Haematology: No effects
- Urinalysis: No effects
- Organ weights: No effects
- Gross pathology: No effects
- Histopathology: No effects

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Only two standard parameters were studied: body weight and survival. Background concentration in the diet varied between 0.1 and 1.0% of SiO2 (w/w). Nitrogen and phosphorous retention/excretion was measured only in the males at the end of the exposure period.
Principles of method if other than guideline:
Oral exposure of weanling rats via drinking water for 180 days.
The study was conducted to assess the influence of silica in the diet on growth and nutrient balance.
GLP compliance:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS
- Age: Weanling
Route of administration:
oral: drinking water
Vehicle:
water
Duration of treatment / exposure:
180 d (m-f) + 17 days (m)
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
789.5 and 1587 mg sodium  silicate/L
Basis:
nominal in water
Remarks:
Doses / Concentrations:
600 and 1200 mg SiO2/l
Basis:

No. of animals per sex per dose:
6
Control animals:
yes
Details on study design:
Post-exposure period: no
Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY: 
- Mortality: registered with unknown frequency
- Body weight: registered every week
- Urinalysis: nitrogen and phosphorous registered daily from day 181-197 in males. 
Other examinations:
Analysis of faeces: nitrogen and phosphorous registered daily from day 181-197 in males.
Dose descriptor:
NOAEL
Effect level:
> 159 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: no effects observed
Critical effects observed:
not specified

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: None
- Clinical signs: no effects
- Body weight gain: Some statistically significant differences in body weight between experimental groups and controls were registered, but these were small (6% or less), not consistent and not dose related.
- Urinalysis: significant, but not dose-related effects on nitrogen and  phosphorus retention (p<0.05)
- Other: In the male low dose group nitrogen retention was 50% lower that in the control group, while in the high dose
group no such difference was observed. In a repeat experiment no clear and significant differences in nitrogen
retention were found. In both experiments phosphorous retention seemed somewhat increased in the male high dose
groups (approximately 12%), while in the low dose groups no effect of treatment was seen.

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented study, but test substance not clearly identified and background exposure through diet not stated.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
no
Species:
dog
Strain:
Beagle
Sex:
male/female
Details on test animals and environmental conditions:
TEST ORGANISMS
- Age: about 6 months (young adult)
- Weight at study initiation:  7-9 kg
Route of administration:
oral: feed
Vehicle:
other: feed
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
2400 mg/kg bw/d
Basis:
other: nominal dose
No. of animals per sex per dose:
8
Control animals:
yes
Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY: 
- Clinical signs: daily
- Mortality: examined daily
- Body weight: recorded weekly
- Food consumption: registered with unknown frequency
- Haematology: registered weekly: total WBC count, differential WBC count, packed cell volume, prothrombine time, serum hemoglobin
- Urinalysis: urinary specific gravity, protein, glucose concentrations and urea nitrogen measured weekly
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): 
- Macroscopic: the weight of not specified organs was registered. 
- Microscopic: A set of tissues was preserved in formalin for histopathology examination. No further information.
Dose descriptor:
LOAEL
Effect level:
2 400 mg/kg bw/day (nominal)
Sex:
male/female
Basis for effect level:
other: gross cortical renal lesions in 15/16 animals
Critical effects observed:
not specified

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: None
- Clinical signs: Polydipsia, polyuria and soft stools observed in a few animals (not quantified). Most animals had soft discoloured faeces occasionally due to unabsorbed compound.
- Body weight gain: No effects
- Food/water consumption: No effects
- Clinical chemistry: No effects
- Haematology: No effects
- Urinalysis: No effects
- Organ weights: No effects
- Gross pathology: Gross cortical lesions of the kidney were observed in 8/8 males and 7/8 females.
- Histopathology: Irritation of the renal tubular epithelium was followed by degenerative and regenerative changes, accompanied by inflammatory cell infiltration into the interstitium in all dogs exhibiting gross renal lesions. These phenomena were not observed in any of the control animals. Animals with renal lesions did not show any impairment of renal function.

Additional information

Oral

Sodium silicate has been tested in repeated oral dose toxicity studies ranging from 28 days to 180 days exposure in rats and dogs. No adverse effects were observed in male and female rats administered the test substance via drinking water for 180 days (Smith et al., 1973). The NOAEL was determined to be > 159 mg/kg bw/day.

In a subchronic study, the only treatment-related effects observed in rats were: polydipsia, polyuria and soft stools at 2400 mg/kg bw/day (Newberne and Wilson, 1970). Dogs exhibited gross renal cortical lesions, polydipsia, polyuria and soft stools at 2400 mg/kg bw/day (Newberne and Wilson, 1970).

Justification for classification or non-classification

Data are not sufficient for classification.