Tin dioxide

Repeated dose toxicity: oral

Administrative data

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: Published literature fulfilled basically scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1973

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In order to investigate repeated toxicity in 28 days of series of tin compounds, Rats were fed on diets containing 0 (control), 0.03, 0.10, 0.30 or 1.00 % of tin dioxide, stannous orthophosphate, oxalate and sulphide, stannous sulphate, stannous oleate, and stannous tartrate of tin for periods of 4 weeks.- Principle of test: The various tin compounds examined were fed to groups
of ten male and ten female rats at dietary levels of 0-0 (control), 0.03, 0.10, 0.30 and 1.00 %
for 28 days. Body weight and food intake were recorded weekly. Haematological examinations
were made on all rats on day 27 using blood from the tip of the tail. Measurements
were made of haemoglobin concentration, packed cell volume and counts of erythrocytes
and leucocytes.
- Short description of test conditions: Animals and diets. Male and female weanling rats from the Institute's Wistar-derivedcolony were housed in groups of five in stainless steel cages with screen bottoms.
- Parameters analysed / observed:At autopsy the liver, kidneys, heart and spleen were weighed and samples of these organs were processed in the usual way for histological examination.

GLP compliance:

no

Remarks:

publication

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tin dioxide

EC Number:

242-159-0

EC Name:

Tin dioxide

Cas Number:

18282-10-5

Molecular formula:

O2Sn

IUPAC Name:

tin(4+) dioxidandiide

Details on test material:

Stannic oxide (pure, E. Merk AG, Darmastad, Germany); in addition other tin compounds were also tested. They were as follows:
stannous orthophosphate, oxalate and sulphide (laboratory reagents, British Drug Houses Ltd., Poole, Dorset), stannous sulphate (Schuchardt AG, Munich, Germany), stannous oleate (K and K Labora- tories Inc., Plainview, N.Y.) and stannous tartrate (Sigma Chemical Co., St. Louis, Mo.).

Test animals

Species:

rat

Strain:

other: weanling rats from the Institutes Wistar-derived colony

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female weanling rats from the Institute's Wistar-derived colony were housed in groups of five in stainless steel cages with screen bottoms. The diet used for both control and treated groups was the Institute's stock diet, with the following percentage composition: soyabean-oil meal, 10; fish meal, 8; meat scraps, 4; dried whey, 2; yellow maize, 29.05; wheat, 36; grass meal, 3; brewer's yeast, 3, complete B-vitamin mixture, 0.1; vitamin-ADEK preparation, 0.6; bone meal, 0.75; trace mineral salt, 0.5; soyabean oil, 3. This diet was found to contain calcium (0.98 %), phosphorus (0.80 %), iron (205 ppm), copper (23 ppm), manganese (85 ppm) and zinc (38 ppm). Test diets were prepared by blending the stock diet and the tin compouds in a Stephan cutter. Diets and tap water were provided ad lib.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The various tin compounds examined were fed to groups of ten male and ten female rats at dietary levels of 0-0 (control), 0.03, 0.10, 0.30 and 1.00 % for 28 days.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Due to stability of these tin compounds, the analytical verification for these substances is unnecessary.

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

Animals were dosed once each day at approximately the same time each day, seven days per week.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: %

Remarks:

Basis:nominal in diet
Control.

Doses / concentrations 2

Dose / conc.:

0.03 other: %

Remarks:

Basis: nominal in diet.

Doses / concentrations 3

Dose / conc.:

0.1 other: %

Remarks:

Basis: nominal in diet

Doses / concentrations 4

Dose / conc.:

0.3 other:

Remarks:

Basis:nominal in diet

Doses / concentrations 5

Dose / conc.:

1 other: %

Remarks:

Basis: nominal in diet

No. of animals per sex per dose:

10 males and 10 famels

Control animals:

yes, concurrent no treatment

Details on study design:

The various tin compounds examined were fed to groups of ten male and ten female rats at dietary levels of 0-0 (control), 0.03, 0.10, 0.30 and 1.00 % for 28 days. Body weight and food intake were recorded weekly. Haematological examinations were made on all rats on day 27 using blood from the tip of the tail. Measurements were made of haemoglobin concentration, packed cell volume and counts of erythrocytes and leucocytes. At autopsy the liver, kidneys, heart and spleen were weighed and samples of these organs were processed in the usual way for histological examination.

Positive control:

not required

Examinations

Observations and examinations performed and frequency:

Body weight and food intake were recorded weekly. Haematological examinations were made on all rats on day 27 using blood from the tip of the tail. Measurements were made of haemoglobin concentration, packed cell volume and counts of erythrocytes and leucocytes. At autopsy the liver, kidneys, heart and spleen were weighed and samples of these organs were processed in the usual way for histological examination.

Sacrifice and pathology:

At autopsy the liver, kidneys, heart and spleen were weighed and samples of these organs were processed in the usual way for histological examination.

Other examinations:

no data

Statistics:

no data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

Rats fed stannic oxide, stannous sulphide and stannous oleate at dietary levels up to 1.0 % gained weight at a normal rate and showed no abnormalities in the haematological data examined, apart from a statistically significant increase in the haematocrit in male rats fed the highest level of stannous sulphide. The absolute and relative weights and the gross and microscopic appearance of the liver, kidneys, heart and spleen were not altered. There was no evidence of any deleterious effects of these tin compounds at dietary levels up to 7900 ppm tin.

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

Rats fed stannic oxide, stannous sulphide and stannous oleate at dietary levels up to 1.0 % gained weight at a normal rate and showed no abnormalities in the haematological data examined.
The absolute and relative weights and the gross and microscopic appearance of the liver, kidneys, heart and spleen were not altered.

Effect levels

Key result

Dose descriptor:

dose level:

Effect level:

>= 7 900 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

7 900 ppm

Organ:

blood

heart

kidney

leucocyte development

liver

Any other information on results incl. tables

The feeding of tin as orthophosphate, sulphate, oxalate and tartrate, however, resulted in considerable growth retardation and distinct indications of anaemia at dietary levels of 0.3 and 1.0 % in both sexes. The reduced gain in body weight was accompanied by a decrease in food intake, but food efficiency was also decreased, at least at the 1.0 % feeding level. The signs of anaemia included decreased haemoglobin levels, haematocrit values and erythrocyte counts. The mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC)of the rats fed the highest level of the active tin compounds were generally slightly lower than in the corresponding controls. Although the differences were not considerable (less than 12 %) most of them were statistically significant (P< 0.05). The white blood cell counts showed the usual wide variation, both among individual rats and among the various groups, but there was no evidence that tin compounds affected the number of leucocytes.

 

None of the organs weighed (liver, kidneys, heart and spleen) was distinctly enlarged, except the livers of females ingesting tin orthophosphate, the relative weights of which showed a dose-related increase at 0.1% and above. Slightly decreased liver-to-body weight ratios occurred in groups exhibiting growth retardation.

 

At autopsy, signs of anaemia (pale eyes and viscera) were observed in animals fed the 1% dose level of tin chloride, tin oxalate or tin sulphate. In addition, rats fed on diets containing 1% tin chloride or 1% tin orthophosphate showed slightly distended small and large intestines.

Microscopic examination revealed distinct changes in the livers of males and females fed 1% of each of the various tin compounds found to be capable of inducing anaemia and growth retardation. The changes consisted of clearly homogeneous liver cell cytoplasm and a slight but definite oval cell type hyperplasia of bile ducts. Similar hepatic alterations, though of a lesser degree and frequency, were found in rats fed 0-3 % dietary levels of tin chloride, tin oxalate or tin orthophosphate. The histological appearance of the kidneys, heart and spleen was unremarkable in all cases.

Applicant's summary and conclusion

Conclusions:

There was no evidence of any deleterious effects of tin dioxide at dietary levels up to 7900 ppm tin, corresponding to 510 mg/Kg calculated NOAEL. Calculation was made using standard food intake and body weight of rats.

Executive summary:

There were marked differences in the toxicity of various oxides and salts of tin in rats when given by oral administration. In a study, groups of rats (Wistar; n=10/sex/group) were fed diets containing 0, 0.03, 0.10, 0.30, or 1.00% of various tin salts or oxides for periods of 4 weeks for Tin (IV) dioxide, stannous orthophosphate, oxalate and sulphide, stannous sulphate, stannous oleate and stannous tartrate. Effects on behaviour, mortality, body weights, food consumption, blood, urine, biochemical parameters, and organ weights were examined; and gross microscopic examinations were performed. No adverse effects were noted at any dose of tin dioxides, as well as stannous sulphide and oleate. However, severe growth retardation, decreased food efficiency, slight anaemia, and slight histological changes in the liver were observed with 0.3% or more of orthophosphate, sulphate, oxalate, and tartrate.

Rats fed stannic oxide, stannous sulphide and stannous oleate at dietary levels up to 1.0 % gained weight at a normal rate and showed no abnormalities in the haematological data examined, apart from a statistically significant increase in the haematocrit in male rats fed the highest level of stannous sulphide. The absolute and relative weights and the gross and microscopic appearance of the liver, kidneys, heart and spleen were not altered.

There was no evidence of any deleterious effects of these tin compounds at dietary levels up to 7900 ppm tin.