Disodium metasilicate

Endpoint summary

Description of key information

NOAEL (rats): 227 mg/kg bw/day
NOAEL (mice): 260 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

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 limited number of parameters studied.

Principles of method if other than guideline:

Feeding study conducted to study the effects of silicon-deficiency and the possibility to overcome this deficiency using different silicon sources.

GLP compliance:

no

Limit test:

no

Species:

other: turkey

Strain:

other: Nicholas

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: 4-6 weeks
- Weight at study initiation: 54.3 g (760 g after 4 weeks)

Route of administration:

oral: feed

Vehicle:

other: 28% protein, dextrose-casein type formulated dietdiet

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0, 270 ppm Si corresponding to 0 and 2039 mg Na2SiO3x5H2O/kg  diet
Basis:
nominal in diet

No. of animals per sex per dose:

18

Control animals:

yes

Observations and examinations performed and frequency:

- Body weight: Registered every week
- Haematology: Hemoglobin, hematocrit recorded at necropsy
- Biochemistry: Plasma Ca, Mg, Zn, P, Cu and plasma cholesterol, alkaline phosphatase activity. Cu and Zn in nitric acid digests of liver.

Sacrifice and pathology:

- Macroscopic: Heart, liver, tibia (organ weights only)

Other examinations:

Concentrations of Cu and Zn in excised organs

Statistics:

General linear model (GLM) analysis of variance (ANOVA); Fisher protected least square difference (LSD) test; standard error of the means calculated from mean squares

Critical effects observed:

not specified

- Time of death: no mortality
- Number of deaths: no mortality

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality and time to death: None
- Body weight gain: No effects
- Clinical chemistry: increased P (6%) and decreased Cu (29%) at p<0.05 level.
- Haematology: No effects
- Organ weights: No effects

Reference 2

Endpoint:

sub-chronic 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 limited number of parameters studied.

Principles of method if other than guideline:

Feeding study conducted to study the effects of silicon-deficiency and the possibility to overcome this deficiency using different silicon sources.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: 8-12 weeks
- Weight at study initiation: 45.0 g (257 g after 8 weeks)

Route of administration:

oral: feed

Vehicle:

other: dextrose-egg-albumin type diet

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

8 weeks

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0, 500 ppm Si corresponding to 0 and 3777 mg Na2SiO3x5H2O/kg  diet
Basis:
nominal in diet

No. of animals per sex per dose:

18

Control animals:

yes

Observations and examinations performed and frequency:

- Body weight: Registered once a week
- Haematology: Hemoglobin, hematocrit registered at necropsy
- Biochemistry: Plasma minerals (Ca, P, Mg, Cu, Zn), plasma cholesterol, alkaline phosphatase activity registered. Cu and Zn was registered in nitric acid digests of liver and heart tissues.

Sacrifice and pathology:

- Macroscopic: Heart, liver, femurs (organ weights only)

Other examinations:

Concentrations of Cu and Zn in excised organs were measured.

Statistics:

General linear model (GLM) analysis of variance (ANOVA); Fisher protected least square difference (LSD) test; standard error of the means calculated from mean squares.

Critical effects observed:

not specified

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: No mortality
- Body weight gain: No effects
- Clinical chemistry: decreased Ca (8%), Mg (7%) at p<0.05 level
- Haematology: No effects
- Organ weights: No effects
- Other: decreased Zn in liver (8%) at p<0.05 level

Reference 3

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: Study performed according to basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: 7 weeks

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 months

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
200, 600 and 1800 ppm
Basis:
nominal in water

No. of animals per sex per dose:

5

Control animals:

yes

Observations and examinations performed and frequency:

- Clinical signs: daily
- Mortality: daily
- Body weight: once a week
- Food consumption: once a week
- Water consumption: measured daily 
- Haematology: after the test period erythrocytes and leukocytes were counted, hemoglobin value, blood cell volume and leukocyte percentage
- Biochemistry:  after the test period gamma-GOT, gamma-GPT and alkali phosphatase activity measurement
- Urinalysis: after the test period measurements were made on pH-value, sugar, protein, ketone and blood value.

Sacrifice and pathology:

- Macroscopic: wet weight of liver, kidney, heart, lung, spleen, suprarenal glands, thymus, thyroid gland, testicles and ovaries. Also dissected: pancreas, intestines, stomachs, bone marrow.
- Microscopic: liver, kidney, heart, lung, spleen, suprarenal glands, thymus, thyroid gland, testicles and ovaries were fixed with 10% formalin, packed in paraffin, cut into thin sections and subjected to hematoxylin and eosin staining.

Dose descriptor:

NOAEL

Effect level:

> 227 - 237 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: overall effects

Critical effects observed:

not specified

No clearly treatment related effects at tested dose levels of 200, 600 and 1800 ppm (corresponding to 26.4, 76.2 and
227.1 mg/kg/day, respectively, for males; and 32.1, 97.6 and 237.2  mg/kg/day, respectively, for females).

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: None
- Clinical signs: No effects
- 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: Except for the kidneys, no morphological changes have  been observed in the organs examined. The observed

histological changes in the kidneys (tubule wall calcinosis, glomerular swelling, tubule  swelling, weakening of the renal tubule cell

walls and dilation of the  tubule lumen) were not dose-related and occurred also in the controls.  Cylindrical inclusions in the renal

tubular cells were only observed in  the medium dosage group.

Reference 4

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: Study performed according to basic scientific principles, study report is unclear in some points.

Principles of method if other than guideline:

no data

GLP compliance:

no

Limit test:

no

Species:

mouse

Strain:

other: ddy

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: 4 weeks

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

continuously

Remarks:

Doses / Concentrations:
300, 900, 2700 ppm (males), 333, 1000, 3000 ppm (females)
Basis:
nominal in water

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

Post-exposure period: no

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS AND FREQUENCY: 
- Clinical signs: registered once daily
- Mortality: registered once daily
- Body weight: registered once a week
- Food consumption: registered once a week
- Water consumption: registered twice a week
- Haematology: erythrocyte count, leucocyte count, haemoglobin, haematocrit, blood serum protein content, leucocyte composition.
- Biochemistry: S-GOT, S-GTP, S-AlP (alkali phosphatase), bilirubin, blood glucose, BUN, cholesterol, A/G, potassium, sodium, chloride.
- Urinalysis: performed at the end of the study. pH, sugar (assumed to be glucose), protein, ketone, blood concentration, urinobilinogen.

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC): 
- Macroscopic: the wet weight of liver, kidney, spleen, suprarenal glands, thyroid glands, testicles, pituitary glands, heart, lung, brain, ovary was registered. The organs of the thoracic and abdominal cavity were examined macroscopically
- Microscopic: liver, kidney, spleen, suprarenal glands, thyroid glands, testicles, pituitary glands, heart, ovary, lung, brain, pancreas, stomach, duodenum, jejenum, ileum, cecum, rectum, urinary bladder, prostate, uterus, mammary glands, arteries, bone marrow, lymphatic glands were fixed in 10% formalin, packed in paraffin, cut into thin sections, subjected to haematoxylin and eosin staining and examined microscopically

Dose descriptor:

NOAEL

Effect level:

260 - 284 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: overall effects

Dose descriptor:

LOAEL

Effect level:

716 - 892 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: organ weights

Critical effects observed:

not specified

ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: 
males:
nominal dose   300       900       2700 ppm
actual intake  2.4-2.5   6.6-7.0   19.4-20.8 mg/animal/d
actual dose    96-100    264-280   776-832 mg/kg bw/d

females:
nominal dose   333       1000      3000 ppm
actual intake  2.2-2.6   6.5-7.1   17.9-22.3 mg/animal/d
actual dose    88-104    260-284   716-892 mg/kg bw/d
(calculations are based on an average body weight for mice of 25 g)

- Time of death: no mortality
- Number of deaths at each dose: no mortality

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: no mortality
- Clinical signs: no treatment-related effects
- Body weight gain: no treatment-related effects 
- Food/water consumption: there were no effects on food and water consumption. 
- Clinical chemistry: no effects 
- Haematology: There was an increase of the haematocrit level in the female high dose group. The leucocyte count in females
was significantly reduced in the low and medium dose group, and reduced in the highest dose group.
- Urinalysis: the protein concentration in all female exposure groups was slightly increased compared with the control group.
- Organ weights: the relative pituitary gland weight in females was reduced in all dose groups compared to the control, statistically significant only in the highest dose group. The relative liver weight in males was increased in all dose groups compared to control group,significantly in the low and medium

dose group. With respect to the reproductive organs examined, the following wet  weights (g) were determined:

                   Testes             Ovaries
               right    left       right   left

control        0.13     0.14       8.4     7.3
2700 ppm     0.14     0.14       7.7     7.4
900 ppm       0.13     0.13       9.7     9.1
300 ppm       0.13     0.12       8.3     8.4

- Gross pathology: see histopathology
- Histopathology: no treatment-related effects

Reference 5

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study report provides only summary of data, no tables with data from individual animals are given. In addition, inconsistencies were found. For example, the dose levels under "method" and "results" do not correlate, so the "results" section may have been switched with the "results" section of the 14 days mouse study, and therefore the data are tainted with uncertaintanties.

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Species:

mouse

Strain:

other: ddy

Sex:

male/female

Route of administration:

oral: gavage

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
37.5, 75, 150, 300, 600 mg/kg
Basis:

Control animals:

yes

Details on study design:

Post-exposure period: no

Dose descriptor:

NOAEL

Effect level:

75 mg/kg bw/day (nominal)

Sex:

male/female

Dose descriptor:

LOAEL

Effect level:

150 mg/kg bw/day (nominal)

Sex:

male/female

Critical effects observed:

not specified

RS-Freetext:
NOAEL: 75 mg/kg bw/d 
LOAEL: 150 mg/kg bw/d 
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
- Time of death: no mortalities
- Number of deaths at each dose: no mortalities
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: no mortalities
- Clinical signs: animals administered 75 mg/kg bw/d or
less, showed no effects. At dose level 150 mg/kg bw/d and
above, the animals became lethargic immediately after
administration. Animals administered 300 or 600 mg/kg bw/d
became agitated and reacted more intensely to external
stimuli. In the highest dose group rough hair coat and dull
fur was observed from the fourth exposure day on.
- Body weight gain: in animals exposed to 600 mg/kg bw/d
reduced body weight increase was observed from the third day
of exposure. Females recovered on the sixth day of exposure.
No further details are given.
- Food/water consumption: not reported
- Ophthalmoscopic examination: not reported
- Clinical chemistry: not reported
- Haematology: not reported
- Urinalysis: not reported
- Organ weights: not reported
- Gross pathology: 2 males administered 600 mg/kg bw/d had
white, hazy spots on the horizontally neighbouring faces of
the right internal lobe of the liver, while 2 females in the
same dose group had a coarse kidney surface (the surface of
the kidney in one animals had a faded colour, the other
showed white hazy spots).
- Histopathology: localised bleeding in the thymus glands
and thickened uterus linings were sporadically observed in
all groups.
- Other: the renal effects reported in the abstract (Ito,
1986) were not mentioned in the study report.
STATISTICAL RESULTS: not reported

Reference 6

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study report provides only summary of data, no tables with data from individual animals are given. In addition, inconsistencies were found. For example, the dose levels under "method" and "results" do not correlate, so the "results" section may have been switched with the "results" section of the 14 days mouse study, and therefore the data are tainted with uncertaintanties.

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Species:

rat

Strain:

other: Wistar-SLC

Sex:

male/female

Route of administration:

oral: gavage

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
Females: 62.5, 125, 250, 500 or 1000 mg/kg bw/d. Males: 37.5, 75, 150, 300, 600 mg/kg bw/d.
Basis:

Control animals:

yes

Details on study design:

Post-exposure period: no

Dose descriptor:

NOAEL

Effect level:

125 mg/kg bw/day (nominal)

Sex:

male/female

Dose descriptor:

LOAEL

Effect level:

250 mg/kg bw/day (nominal)

Sex:

male/female

Critical effects observed:

not specified

RS-Freetext:
NOAEL: 125 mg/kg bw/d 
LOAEL: 250 mg/kg bw/d
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX
- Time of death: no mortalities
- Number of deaths at each dose: no mortalities
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: 3/5 females administered 1000 mg/kg bw/d  (2 died in the first week; 1 in the second week). 2/5 females  administered 500 mg/kg bw/d (1 died in the first week; 1 in the second  week), 2/5 males administered 600 mg/kg bw/d (both died in the first  week).
- Clinical signs: a lower activity level, a lower level of
reaction to external stimuli, and fading skin colour was
observed from the first day of dosing in females exposed to
1000 mg/kg bw/d, and from day 3 in females administered 600
mg/kg bw/d. In general, females in these dose groups had
secretion of nasal mucus and opacified body hairs, these
symptoms improved from day 11 onward. 
- Body weight gain: females administered 250 mg/kg bw/d had
reduced body weight gain day 14 of the exposure, and females
administered 300 mg/kg on day 7 and 14 of exposure. Females
administered 250, males administered 300 mg/kg bw/d and all
higher dose groups showed a reduced body weight gain during
administration. Males recovered from the 14th day on. As no
further details are given, it is unsure whether the reduced
body weight gain is given for the specified days or the 7
preceding days.
- Food/water consumption: not reported
- Ophthalmoscopic examination: not reported
- Clinical chemistry: not reported
- Haematology: not reported
- Urinalysis: not reported
- Organ weights: not reported
- Gross pathology: not reported
- Histopathology: in surviving animals, localised bleeding
in the thymus glands, lungs and semi-transparent fluid in
the uterus were sporadically observed in all groups including the  controls. In the animals that died there was considerable bleeding in the
stomach. The renal effects reported in the abstract (Ito, 1986) were not  mentioned in the study report.
- Other: not reported
STATISTICAL RESULTS: not reported

Reference 7

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study performed according to basic scientific principles, however, the report contains inconsistencies and incomplete tables that make the credibility questionable.

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Species:

rat

Strain:

other: Wistar-DLC

Sex:

male/female

Route of administration:

oral: drinking water

Duration of treatment / exposure:

3 months

Frequency of treatment:

continously

Remarks:

Doses / Concentrations:
23, 47, 110 mg/d (males), 21, 37, 84 mg/d (females)
Basis:

Control animals:

yes

Details on study design:

Post-exposure period: no

Critical effects observed:

not specified

RS-Freetext:
NOAEL (NOEL), LOAEL (LOEL): Not possible to assess.
ACTUAL DOSE RECEIVED BY DOSE LEVEL BY SEX: the actual dose
received was given as "individual specimen intake", the
cumulative intake over the entire exposure period. The
intake has been divided by 90 to find the average daily
intake. Males administered the nominal dose 750, 1500 or
3000 ppm, had an actual intake during the exposure period of
23, 47 or 110 mg/d, respectively. Females had an actual
intake during the exposure period of 21, 37 or 84 mg/d,
respectively. Exact dosing regime unsure due to a confusing
study report.
- Time of death: no mortality
- Number of deaths at each dose: no mortality 
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Mortality and time to death: no mortality
- Clinical signs: no effects
- Body weight gain: no significant effects 
- Food/water consumption: there were no effects on food
consumption. The water consumption was not mentioned in the
report.
- Ophthalmoscopic examination: not reported
- Clinical chemistry: Increase in S-GOT in high and medium
male dose groups, decrease in high female dose group.
Increase in S-GPT in males in high and medium dose group.
Increase in cholesterol level in all male exposure groups.
Decrease in Na-levels in all male exposure groups, increase
in female high dose group. Cl-levels decreased in male high
dose group.  
- Haematology: the erythrocytes count can not be assessed as the report  contains a contradiction between the text and the respective table. An  increase of N-seg and decrease of lymphocytes was observed in the medium  and high female dose groups.
- Urinalysis: the protein content was increased in the high
dose groups.
- Organ weights: a decrease in weight was observed for the
right seminal glands of males exposed to 3000 ppm, for
adrenal glands in all exposed male groups, and pituitary
bodies in all exposed male groups. It is not stated whether
these changes are statistically significant. in the corresponding table  the column indicating the organs is missing.
- Gross pathology: not reported
- Histopathology: no treatment-related effects
- Other: the renal effects referred to in the abstract (Ito,
1986) are not mentioned in the study report.
STATISTICAL RESULTS: not reported

Reference 8

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: High mortality in all groups from month 6 onwards, including control.

Principles of method if other than guideline:

Method: other

GLP compliance:

no

Species:

rat

Strain:

other: Wistar-SLC

Sex:

male/female

Route of administration:

oral: drinking water

Duration of treatment / exposure:

14 months

Frequency of treatment:

continously

Remarks:

Doses / Concentrations:
167, 500, 1500 ppm
Basis:

Control animals:

no

Details on study design:

Post-exposure period: no

Critical effects observed:

not specified

RS-Freetext:
MORTALITY AND TIME TO DEATH: there were sporadical deaths in
all groups from the sixth month of exposure onward, with
the number increasing from month 12. The study was
terminated in month 14 due to difficulties in continuing for
24 months as planned. The exact number of mortalities is not
specified. Deaths were caused by pneumonia.
CLINICAL SIGNS: no significant effects
BODY WEIGHT GAIN: 2-3 months after exposure started, the
medium dose group had a reduced body weight gain. The same
was observed in the low dose group exposure month 3-7. The
effects were transient.
FOOD/WATER CONSUMPTION: the food intake was slightly low in
the female low dose group after the first month of exposure,
and in the male low dose group after month 3 of exposure.
The article states that later there were no significant
changes, however, the length of the period with reduced food
intake is unknown.
OPHTALMOSCOPIC EXAMINATION: not reported
CLINICAL CHEMISTRY: Females in the high dose group had a decreased  glucose level (14 months) and an increase in A/G (12 months). The BUN  increased in females administered medium and high doses (after 6 and 12  months'
exposure), and decreased in males exposed to the medium and
high doses for 12 months. A decreased in sodium
concentration was observed in the female high and medium
dose groups (six months).   
HAEMATOLOGY: the haematocrit level in all exposed male
groups was significantly decreased after 14 months of
exposure, compared to the control group, but within the
expected range according to the authors of the report. The
significant changes in leucocyte composition were as
follows: increase of N-Seg in the male medium dose group at
6 months; increase of eosinophils and monocytes in the male
high dose group, increase of basophiles in the female high
and medium dose group, increase of lymphocytes and decrease
of N-Seg in the female low dose group after 12 months'
exposure; decrease of lymphocytes in the male medium dose
group and increase of monocytes in all female exposure
groups after 14 months of dosing.
URINALYSIS: pH in the male high dose group after six months'
exposure was 6.5-9.0 compared to 7.0-7.5 in the control
group. This range was not registered after 12 or 14 months
of exposure. The protein concentration in the male high dose
group after 12 months of exposure was higher than for the
control group, but not after 6 or 14 months of exposure.
ORGAN WEIGHTS: all results are statistically significant,
and reported after 14 months of exposure. Males in the high
and low dose groups had an increase in thyroid gland weight.
A weight decrease was observed for the livers of males in
low and high dose groups, the left ovary of females in the
medium and high dose groups and the hearts and brains of all
exposed females. The thymus glands could not be weighed due
to fatty degeneration.
GROSS PATHOLOGY: see histopathology
HISTOPATHOLOGY: 3/40 males in the high dose group had
purulent pneumonia after 14 months' exposure.
OTHER: no significant effects were discovered by electron
microscopy of liver tissue. The renal effects mentioned in
the abstract (Ito, 1986) are not present in significant
numbers.
TIME TO TUMOURS: no significant effects
STATISTICAL RESULTS: not reported

Reference 9

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Unsuitable test system as it concerns a study on the growth promoting effects of silicon and not a toxicology study. Furthermore, many relevant parameters are not evaluated.

Principles of method if other than guideline:

26 day feeding study

GLP compliance:

no

Species:

rat

Strain:

Fischer 344

Sex:

male

Route of administration:

oral: feed

Duration of treatment / exposure:

26 days

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
10 and 50 mg of silicon/100g diet and lower, not specified levels
Basis:

Control animals:

yes

Critical effects observed:

not specified

RS-Freetext:
Tooth pigmentation, hairloss, seborrhoea, loss of tonicity
observed.
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
- Clinical signs: Significant improvements of tooth
pigmentation (21%), compared to animals on silicate-free
diet. Hairloss, seborrhoea and loss of tonicity is probabaly
due to the lack of other minerals in the diet.
- Body weight gain: Increased 25-34% at p<0.005 level. Lower
levels of silicon gave statistically insignificant results.
- Gross pathology: No effects
OTHER: Silicon deficiency causes retarded skull growth

Additional information

Oral

Repeated oral dose toxicity studies with disodium metasilicate ranging from 4 weeks to 3 months have been conducted with rats, mice and turkeys. The only treatment-related effects observed in rats were: reduction of blood plasma Ca and Mg and liver Zn concentrations at 1259 mg/kg bw/d (sodium metasilicate, pentahydrate; 8 weeks exposure). In female mice, a reduced pituitary gland weight was observed at 716 - 892 mg/kg bw/d (disodium metasilicate; 3 months exposure). In turkeys, blood plasma phosphate was increased and Cu decreased at 2039 mg/kg diet (disodium metasilicate, pentahydrate; 8 weeks exposure).

From these studies a NOAEL (90 d) of 227 - 237 mg/kg bw/d and of 260-284 mg/kg bw/d can be deduced for rats and mice, respectively.

Justification for classification or non-classification

Data are not sufficient for classification.