Hydrothermal synthesis product of calcium oxide, quartz and water

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

other company data

Title:

Unnamed

Year:

1953

Report date:

1953

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1956

Report date:

1956

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

Deviations:

yes

Remarks:

limited group size (15 + 15); limited examinations

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Silicic acid, calcium salt

EC Number:

215-710-8

EC Name:

Silicic acid, calcium salt

Cas Number:

1344-95-2

IUPAC Name:

Silicic acid, Calcium salt

Test material form:

solid

Specific details on test material used for the study:

- Name of test material (as cited in study report) = Silene EF
- Composition of test material, percentage of components: SiO2 (64 %); CaO (18 %); Al2O3 (0.6 %); MgO (0.1 %); NaCl (1.5 %)

Test animals

Species:

rat

Strain:

other: albino, Carworth Farm strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: weanling
- Weight at study initiation: averages 70 - 73 g (m, f)
- Fasting period before study: no
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: gelatine (15 g/100 mL water)

Details on oral exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Particular measures: Based on results from the pre-test, the test compound had be administered in moist form
in order to suppress its alkalinity and dustability
- Mixing appropriate amounts: Appropriate amounts of the Silene-gelatine mixtures were mixed
with the basic diet in a twin-shell blender on w/w basis.
The amount of gelatine added to all diets including controls remained constant
throughout the whole experiment.

- Storage temperature of food: no data

- Dosage regimen: The high-dose groups had accustom to the diet containing higher levels of Silene:
Therefore, gradual increase in Silene content:
7.5 % group: increase from 5 to 7.5 % after 3 wks;
10 % group: increase from 5 to 7.5 % after 3 wks, further increase from 7,5 to 10 % after 10 wks.

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 years

Frequency of treatment:

continuous

Doses / concentrations

Remarks:

Doses / Concentrations:
1.0, 5.0, 7.5, and 10 % (w/w) in feed, 7.5 and 10 % after an acclimation period to higher levels (see "Diet Preparation" above)
Basis:
nominal in diet

No. of animals per sex per dose:

15

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: no data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: weekly


DETAILED CLINICAL OBSERVATIONS: Yes


BODY WEIGHT: Yes (see report, Table 41, 43, )
- Time schedule for examinations: weekly


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) (see Report, Table 42, 44, 45)
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes (Table 45 + 46)
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes (Table 45)


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages
from the consumption and body weight gain data: Yes


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


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: Yes
- Time schedule for collection of blood: start, 13, 52 and 104 wks
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: start (5 m, 5 f), 13, 52 and 104 wks (3 m, 3 f each group and interval)
- Parameters checked in table 47 were examined: hemoglobin, total red and white blood cell count, differential leukocyte picture


CLINICAL CHEMISTRY: No data


URINALYSIS: Yes (pH measurement)
- Time schedule for collection of urine: during wk 102
- Metabolism cages used for collection of urine: No, individually, in void urine of 5 m and 5 f of each group
- Animals fasted: No
- Parameters checked in table 48 were examined: pH


NEUROBEHAVIOURAL EXAMINATION: No


OTHER:
ANALYSIS of the FECES (see Report, Table 49)
- silicon dioxide content: prior to termination of the experiment

ANALYSIS of TISSUE Sections (see Report, Table 52)
- silicon dioxide content: upon termination of the experiment
(kidney, liver, spleen, cardiac muscle, skeletal muscle, and testes:
from 6 m and 6 f of each dose level, tissues of 3 animals of each sex pooled for analysis (2 replicates)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

ORGAN WEIGHTS: Yes (see table 51)
liver, kidneys, and spleen (both sexes, each group)

HISTOPATHOLOGY: Yes (see table 50)
Tissues from 6 m and 6 f each dose level and control preserved in formalin:
thyroid, lung, heart, liver, kidney, stomach, large and small intestine, pancreas, spleen,
adrenal, urinary bladder, gonads, bone marrow, and skeletal muscle

Statistics:

no data, arithmetic means plus S.D., Fisher Student test for pH in urine

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

effects observed, treatment-related

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not specified

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
survival comparable to controls for all dose groups (Tab. 45)
Prior to death: weight loss and signs of pneumonitis in majority of animals due to overwhelming respiratory infection


BODY WEIGHT AND WEIGHT GAIN
1 %: comparable to control (m + f)
5 %: males with very slight retardation, not statistically significant;
females with growth retardation until wk 52, from wk 78 - 80 comparable to control
7.5 %: males with significant growth retardation (bw approx. -9 % at termination)
females comparable to development in the 5% group
10 %: males and females significant growth retardation, less pronounced in females (bw approx. -11 % for males at termination)


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Food consumption increased at 5 % and higher due to the increase in inert fraction in the diet.
Compound intake: mean daily intake calculated per rat based on food consumption

FOOD EFFICIENCY
decreased dose-related:
1 %: no significant difference from the control, or only slight decreasing trend (Table 46)
5 %: ~90 % of control (m); ~85 % of control (f)
7.5 % ~82 % of control (m); ~75 % of control (f)
10 % ~70 % of control (m); ~70 % of control (f)


URINALYSIS
slightly increasing trend in the high-dose groups as compared to controls (Tab. 48).


ORGAN WEIGHTS
no effect discernible (Tab. 51)


GROSS PATHOLOGY
1 and 5%: No gross lesions attributable to the treatment
10 % level: Calculi consisting of high concentration of CaCO3 and some SiO2 in the intestine or
brittle in the urinary bladder in isolated cases, which may have caused the animals´death.
7.5 and 10 % level: Supply of body fat somewhat less than of controls
Bile-duct dilations and dilation of the portal vein (histologically: impression of cholangitis)
in isolated cases (not noted in other groups);
tissue nodules in the liver in isolated cases (not noted in other groups).


HISTOPATHOLOGY: NON-NEOPLASTIC
comparable to controls



OTHER FINDINGS

SILICON in TISSUES (see also 7.1 Toxikokinetics...)
There was a dose-related increase of Si in the kidney and liver, but not in the other organs examined:
The increase was more marked in males than in females.

Kidney at 5 % level: approx. 3x background (m), no or only slight increase (f)
at 10 % level: approx. 20x background (m), approx. 15x background (f)

Liver at 5 % level: approx. 2x background (m), no or only slight increase (f)
at 10 % level: approx. 3x background (m), approx. 3x background (f)

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

5 other: % in diet

Sex:

male/female

Basis for effect level:

body weight and weight gain

gross pathology

2

Key result

Dose descriptor:

LOAEL

Effect level:

7.5 other: % in diet

Sex:

male/female

Basis for effect level:

other: body weight; gross pathology

3

Key result

Dose descriptor:

NOAEL

Effect level:

ca. 2 500 - ca. 3 200 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: estimated from Report: Compound consumed per rat (Tab. 45) related to mean body weights (Tables 43 and 44)

Target system / organ toxicity

Key result

Critical effects observed:

no