Disodium metasilicate

Carcinogenicity

Description of key information

No reliable data available. Disodium metasilicate does not carry any structural alerts for carcinogenicity.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: 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:

Combined chronic toxicity/carcinogenicity study. The study was ended after 14 months instead of 2 years. Application via drinking water.

GLP compliance:

no

Species:

rat

Strain:

other: Wistar-SLC

Sex:

male/female

Route of administration:

oral: drinking water

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 months

Frequency of treatment:

continuous

Remarks:

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

Remarks:

Doses / Concentrations:
16.7, 50  and 150 mg/kg bw/d
Basis:
other: calculated dose

No. of animals per sex per dose:

40

Control animals:

yes

Details on study design:

Post-exposure period: no

Observations and examinations performed and frequency:

- Body weight: registered once a week
- Food consumption: registered twice a week
- Water consumption: registered twice a week
- Clinical signs: registered daily
- Mortality: registered daily
- Macroscopic examination: all organs in the thoracic and abdominal cavity were examined at necropsy 
- Ophthalmoscopic examination: not reported - Haematology: erythrocyte count, leucocyte count, haemoglobin, haematocrit, blood serum protein, leucocyte composition
- Clinical chemistry: 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, urobilinogen.

Sacrifice and pathology:

- Macroscopic: liver, kidney, spleen, suprarenal glands, thymus, thyroid glands, testicles, pituitary glands, heart, lung, brain, ovary.
- Microscopic: liver, kidney, spleen, suprarenal glands, thyroid glands, testicles, pituitary glands, heart, lung, brain, pancreas, thymus, ovary, stomach, duodenum, jejenum, ileum, cecum, rectum, urinary bladder, prostate, uterus, arteries, lymphatic glands, bone marrow and mammary glands were fixed in 10% formalin, packed in paraffin, cut into thin sections, subjected to haematoxylin and eosin staining and examined microscopically.

Other examinations:

After 6 and 12 months of the exposure period, necropsy was performed on 6 males and six females from each group. Animals that died during the exposure period were necropsied. Liver tissue was prepared for examination by light microscope and electronmicroscope by cutting it into thin slices, which were fixed with 2% glutaraldehyde and thereafter fixed with 2% osmic acid solution. After dehydration with ethanol the fixed tissue specimen was packed in Epon 812, before subjecting to uranyl acetate and lead nitrate staining. 
Combined chronic toxicity/carcinogenicity study. The study was ended after 14 months instead of 2 years, due to high mortality.

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

MORTALITY AND TIME TO DEATH:

There were sporadical deaths in all groups from the sixth month of exposure forward, 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.

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.

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 monophils 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

Justification for classification or non-classification

The available data is conclusive but not sufficient for classification.