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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

From the studies, it is concluded that dietary exposure to levels of Tin (II) oxide and Tin (IV) dioxide up to 1% for 13 and 4 weeks respectively, did not induce any effect in rats.

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: Published literature fulfilled basically scientific principles.
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
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.
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.
Dose / conc.:
0 other: %
Remarks:
Basis:nominal in diet
Control.
Dose / conc.:
0.03 other: %
Remarks:
Basis: nominal in diet.
Dose / conc.:
0.1 other: %
Remarks:
Basis: nominal in diet
Dose / conc.:
0.3 other:
Remarks:
Basis:nominal in diet
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
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
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.
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
Key result
Critical effects observed:
no
Lowest effective dose / conc.:
7 900 ppm
Organ:
blood
heart
kidney
leucocyte development
liver

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.

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.

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:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Published literature fulfilled basic scientific principles. From existing studies of toxicokinetic profiles of Tin (IV) dioxide and Tin (II) oxide, it can be concluded that the toxicokinetic profiles of these two substances appear to be similar. Minor differences between Tin (II) and Tin (IV) in their absorption and distribution indicate that Tin (II) may be a bit more toxic than Tin (IV). Therefore Tin (II) oxide can be used as a structural surrogate for Tin (IV) dioxide in the 90 days repeated toxicity test.
Qualifier:
no guideline followed
Principles of method if other than guideline:
In order to investigate repeated toxicity in 90 days of series of tin compounds, Two tin compounds, stannous oxide (SnO) and stannous chloride (SnCI2•2H20) examined were fed to groups of ten male and ten female rats at dietary levels of 0 (control), 0.03, 0.10, 0.30 and 1.00 % for 90 days.
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
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.
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Two tin compounds, stannous oxide (SnO) and stannous chloride (SnCI2•2H2O) were examined in 13-wk feeding studies. Each of these compounds was 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 90 days.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Due to stability of tin compounds, the analytical verification for these substances is unnecessary.
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
Animals were dosed once each day at approximately the same time each day, seven days per week.
Remarks:
Doses / Concentrations:
0%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0.03%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0.1%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0.3%
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
1.0%
Basis:
nominal in diet
No. of animals per sex per dose:
10 males and 10 femels
Control animals:
yes, concurrent no treatment
Details on study design:
Two tin compounds, stannous oxide and stannous chloride were examined in 13-wk feeding studies. Each of these compounds was 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 90 days. Individual body weights were recorded weekly. The food intake of each group was measured at weekly intervals up to wk 4 and in wk 11-12. Haematological studies were carried out at wk 12 and provided measurements of haemoglobin concentration and haematocrit value, counts of red blood cells and total and differential counts of white blood cells. Additional haematological observations were made in the study on tin chloride. These consisted of haemoglobin readings at wk 2, 4, 6 and 9, and terminal determinations of haptoglobin concentration, numbers of reticulocytes and the osmotic resistance of the erythrocytes. Serum activities of glutamic-oxalacetic and glutamic--pyruvic transaminases and of alkaline phosphatase were determined terminally in both experiments. Bilirubin concentrations were measured terminally only in the study with tin chloride.
Urine examinations, including appearance, pH, glucose, protein, occult blood, ketones and microscopy of the sediment were conducted upon pooled samples from each group in wk 13.

The rats fed the highest level of tin chloride were sacrificed after 8 wk because of poor condition and high mortality. Organs and tissues were fixed in buffered formalin. In wk 14, the remaining rats were killed by decapitation and examined for gross changes. The heart, kidneys, liver, spleen, brain, gonads, thymus, thyroid and adrenals were weighed and paraffin-wax sections of these and a wide range of other organs were stained with haematoxylin and eosin. Detailed microscopic examinations were performed on all rats fed 1% tin oxide, on those fed the two highest levels of tin chloride and on the controls. In the rats fed the intermediate levels of tin chloride, only the liver, kidneys and stomach were examined.
Positive control:
no
Observations and examinations performed and frequency:
Individual body weights were recorded weekly. The food intake of each group was measured at weekly intervals up to wk 4 and in wk 11-12. Haematological studies were carried out at wk 12 and provided measurements of haemoglobin concentration and haematocrit value, counts of red blood cells and total and differential counts of white blood cells. Additional haematological observations were made in the study on tin chloride. These consisted of haemoglobin readings at wk 2, 4, 6 and 9, and terminal determinations of haptoglobin concentration, numbers of reticulocytes and the osmotic resistance of the erythrocytes. Serum activities of glutamic-oxalacetic and glutamic--pyruvic transaminases and of alkaline phosphatase were determined terminally in both experiments. Bilirubin concentrations were measured terminally only in the study with tin chloride.
Urine examinations, including appearance, pH, glucose, protein, occult blood, ketones and microscopy of the sediment were conducted upon pooled samples from each group in wk 13.


Sacrifice and pathology:
The rats fed the highest level of tin chloride were sacrificed after 8 wk because of poor condition and high mortality. Organs and tissues were fixed in buffered formalin. In wk 14, the remaining rats were killed by decapitation and examined for gross changes. The heart, kidneys, liver, spleen, brain, gonads, thymus, thyroid and adrenals were weighed and paraffin-wax sections of these and a wide range of other organs were stained with haematoxylin and eosin. Detailed microscopic examinations were performed on all rats fed 1 % tin oxide, on those fed the two highest levels of tin chloride and on the controls. In the rats fed the intermediate levels of tin chloride, only the liver, kidneys and stomach were examined.
Other examinations:
no data
Statistics:
no data
Clinical signs:
no effects observed
Description (incidence and severity):
For Stannous oxide
Mortality:
no mortality observed
Description (incidence):
For Stannous oxide
Body weight and weight changes:
no effects observed
Description (incidence and severity):
For Stannous oxide
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
For Stannous oxide
Food efficiency:
no effects observed
Description (incidence and severity):
For Stannous oxide
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
For Stannous oxide
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Description (incidence and severity):
For Stannous oxide
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
For Stannous oxide
Gross pathological findings:
no effects observed
Description (incidence and severity):
For Stannous oxide
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
For Stannous oxide
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
For Stannous oxide
Details on results:
Stannous oxide:
The feeding of stannous oxide at various dietary levels up to 1.0 % did not cause any noticeable changes in appearance or behaviour, nor in body-weight gain and food intake. The haematological values and serum-enzyme activities were not altered and there were no significant changes in the composition of the urine. No treatment-related differences were observed in the weights of the organs or in the gross and microscopic appearance of the organs examined. Since none of the criteria examined was affected, no details of this study are presented.

Stannous chloride:
The rats fed the diet containing 1 % stannous chloride ate little food and already showed abdominal distension during wk 1. Growth was slow in the first few weeks and stopped completely in males after 4 wk and in females after 6 wk. At wk 8, loss of body weight occurred in seven males and four females and one male died. At wk 9, another three males died. Since several other males were moribund it was decided to discontinue this group and autopsy was performed.
Poor appetite and abdominal distension were observed also at the 0.3 % feeding level during the first 2 wk. However, all rats kept growing, except for one female which lost weight in wk 10 and died in wk 11. It summarizes some of the data on mean body weights, consumption of food and water and food efficiency. The growth retardation that occurred at 1.0 and at 0.3 % during the first 2 wk was associated with a decrease in food consumption. Thereafter body-weight gain and food-intake figures at the 0.3 % level returned to normal. Food intake was relatively low also at the 0.1% level, but only during wk 1. Water intake per unit of food consumed was slightly increased in the 0.3 and 1.0% groups during wk 1.
The haemoglobin values determined at various stages showed decreased levels in the 1.0 and 0.3 % groups in both sexes from wk 4 onwards. At 1.0 % there was a gradual decrease in haemoglobin content, and at 0.3 %, although a gradual rise did occur, it was distinctly slower in the initial stages than that in the controls.
The terminal haematological findings are presented in Table 4 of the pubblication. The mean values of haemoglobin content and cell volume were decreased in both sexes in the group given the 0.3 % diet but the differences from the controls were statistically significant only in males.
Key result
Dose descriptor:
NOAEL
Effect level:
>= 10 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
food consumption and compound intake
Critical effects observed:
not specified

Tin (II) oxide did not induce any effect in rats in repeated dose toxicity studies.

Conclusions:
It suggested that insoluble tin compounds (stannic oxide and stannous oxide) are relatively harmless at dietary levels of 1%, whereas cationic tin compounds soluble in water or dilute acid may be toxic at dietary levels above 0.1%.
Executive summary:

In the test, groups of rats (Wistar; n=10/sex/group) were fed diets containing Tin (II) oxide and stannous chloride at dose of 0, 0.03, 0.10, 0.30, or 1.00% for periods of 13 weeks. 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 oxide. However, severe growth retardation, decreased food efficiency, slight anaemia, and slight histological changes in the liver were observed with 0.3% or more of stannous chloride.

 

The authors concluded that the differences in response to different tin compounds suggested that insoluble tin compounds are relatively harmless whereas cationic tin compounds soluble in water or dilute acid may be toxic at dietary levels above 0.1%. From these studies, it is concluded that dietary exposure to levels of Tin (II) oxide up to 1% for 13 weeks, did not induce any effect in rats.

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The main assumption for this read across approach is that the source substance ionic Tin and the target substance Tin (IV) dioxide NP have a common moiety (Tin ion).
Differences in the valence of atom Sn are expected to exert little effect on the physicalchemical properties of Tin (II) oxide and Tin (IV) dioxide NP, which indicates their toxicokinetic profile should be similar.
Minor differences between Tin (II) and Tin (IV) in their absorption and distribution indicate that Tin (II) may be a bit more toxic than Tin (IV). In addition, soluble inorganic tin like Tin (IV) chloride, Tin (II) fluoride, and Tin (II) chloride with higher water solubility and content of halogen is more toxic than insoluble tin oxides, regardless the dimension. It has to be noted that Tin dioxide bulk form and the Tin Dioxide NP are both highly insoluble in water. This support a read-across argument.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to test item sections for details.
3. ANALOGUE APPROACH JUSTIFICATION
A reliable short-term oral study is available for the source substance ionic Tin (II), showing that there was no evidence of any deleterious effects of these tin compounds at dietary levels up to 7900 ppm tin.
Since the target and the source substance dissociate to the same ion, both target and read-across substance, do share the same toxicological mechanisms and the effects of the target substance is predicted to be equal to the effects of the source substance.
The differences in response to different tin compounds suggested that insoluble tin compounds are relatively harmless whereas cationic tin compounds soluble in water or dilute acid may be toxic at dietary levels above 0.1%. From these studies, it is concluded that dietary exposure to levels of Tin (II) oxide and Tin (IV) dioxide up to 1% for 13 and 4 weeks respectively, did not induce any effect in rats.

The dissolving part of Tin (IV) dioxide contributes mostly to its toxicity (De Groot et al, 1973). The common compound ionic Tin (IV) is solely responsible for the absence or presence of effects. Therefore the same conclusion is valid for the target substance Tin Dioxide NP.
(see also document attached).
Reason / purpose for cross-reference:
read-across source
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 con-taining 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 %
GLP compliance:
no
Remarks:
pubblication
Limit test:
no
Dose / conc.:
0 other: %
Remarks:
Basis: nominal in diet
Control.
Dose / conc.:
0.03 other: %
Remarks:
Basis: nominal in diet
Dose / conc.:
0.1 other: %
Remarks:
Basis: nominal in diet
Dose / conc.:
0.3 other: %
Remarks:
Basis: nominal in diet
Dose / conc.:
1 other: %
Remarks:
Basis: nominal in diet
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
Key result
Critical effects observed:
no
Lowest effective dose / conc.:
7 900 ppm
Organ:
blood
heart
kidney
leucocyte development
liver
Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The main assumption for this read across approach is that the source substance ionic Tin and the target substance Tin (IV) dioxide NP have a common moiety (Tin ion).
Differences in the valence of atom Sn are expected to exert little effect on the physicalchemical properties of Tin (II) oxide and Tin (IV) dioxide NP, which indicates their toxicokinetic profile should be similar.
Minor differences between Tin (II) and Tin (IV) in their absorption and distribution indicate that Tin (II) may be a bit more toxic than Tin (IV). In addition, soluble inorganic tin like Tin (IV) chloride, Tin (II) fluoride, and Tin (II) chloride with higher water solubility and content of halogen is more toxic than insoluble tin oxides, regardless the dimension. It has to be noted that Tin dioxide bulk form and the Tin Dioxide NP are both highly insoluble in water. This support a read-across argument.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to test item sections for details.
3. ANALOGUE APPROACH JUSTIFICATION
A reliable sub-chronic oral study is available for the source substance ionic Tin (II), showing that dietary exposure to levels of Tin (II) oxide up to 1% for 13 weeks, did not induce any effect in rats.
Since the target and the source substance dissociate to the same ion, both target and read-across substance, do share the same toxicological mechanisms and the effects of the target substance is predicted to be equal to the effects of the source substance.
The differences in response to different tin compounds suggested that insoluble tin compounds are relatively harmless whereas cationic tin compounds soluble in water or dilute acid may be toxic at dietary levels above 0.1%. From these studies, it is concluded that dietary exposure to levels of Tin (II) oxide and Tin (IV) dioxide up to 1% for 13 and 4 weeks respectively, did not induce any effect in rats.

The dissolving part of Tin (IV) dioxide contributes mostly to its toxicity (De Groot et al, 1973). The common compound ionic Tin (IV) is solely responsible for the absence or presence of effects. Therefore the same conclusion is valid for the target substance Tin Dioxide NP.
(see also document attached).
Reason / purpose for cross-reference:
read-across source
Qualifier:
no guideline followed
Principles of method if other than guideline:
In order to investigate repeated toxicity in 90 days of series of tin compounds, Two tin compounds, stannous oxide (SnO) and stannous chloride (SnCI2•2H20) examined were fed to groups of ten male and ten female rats at dietary levels of 0 (control), 0.03, 0.10, 0.30 and 1.00 % for 90 days.
GLP compliance:
no
Limit test:
no
Key result
Dose descriptor:
NOAEL
Effect level:
>= 10 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
food consumption and compound intake
Critical effects observed:
not specified
Endpoint conclusion
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
Critical effects observed:
not specified

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
a short-term toxicity study does not need to be conducted because a reliable sub-chronic (90 days) or chronic toxicity study is available, conducted with an appropriate species, dosage, solvent and route of administration
Critical effects observed:
not specified

Additional information

From existing studies of toxicokinetic profiles of Tin (IV) dioxide and Tin (II) oxide, it can be concluded that the toxicokinetic profiles of the two substances appear to be similar. Minor differences between Tin (II) and Tin (IV) in their absorption and distribution indicate that Tin (II) may be a bit more toxic than Tin (IV). Therefore Tin (II) oxide can be used as a structural surrogate for Tin (IV) dioxide in the 90 days repeated toxicity test.

In the test, 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 13 weeks for Tin (II) oxide and 4 weeks for Tin (IV) dioxide, respectively. 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 oxides, 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 stannous chloride, orthophosphate, sulphate, oxalate, and tartrate (De Groot et al, 1973). The authors concluded that the differences in response to different tin compounds suggested that insoluble tin compounds are relatively harmless whereas cationic tin compounds soluble in water or dilute acid may be toxic at dietary levels above 0.1%. From these studies, it is concluded that dietary exposure to levels of Tin (II) oxide and Tin (IV) dioxide up to 1% for 13 and 4 weeks respectively, did not induce any effect in rats.

Therefore the NOAEL of Tin (IV) dioxide was considered to be 1 % in diet for rat (NOECmammal, food_chr). (1% in diet is equivalent to 10000 mg/kg diet)

According to REACH guidance “Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for environment” the NOAELmammal, food_chr= NOECmammal, food_chr/ CONVmammal(CONVmammal for Rattus norvegicus (> 6 weeks) was default as 20). The NOAEL of Tin (IV) dioxide to rat, 500 mg/kg bw per day can be estimated by above method.


Repeated dose toxicity: via oral route - systemic effects (target organ) other: all gross lesions and masses

Justification for classification or non-classification

Based on the NOAEL of 500 mg/kg bw/day is above the criteria value of STOT RE 100 mg/kg bw, the substance is not need to be classified under Regulation (EC) No 1272/2008 for any category of Specific target organ toxicity - repeated exposure. For the same reason it does not satisfy with the classification criteria of Directive 67/548/eec.