Disodium tin trioxide

Endpoint summary

Description of key information

According to the relvant study for subacute chronic toxicity a NOAL of 1 % in diet was determined.

Under consideration of a body of 250g / rat the folowing NOAEL could be calculated from the raw data:

NOAEL (male( = 517.14 mg SnO2/kg bw day

NOAEL(female) 408,57 mg SnO2 /kg bw day.

So the female aninal is the most sensitive species, thus the NOAEL for Sodiums stabbate is 723.01 mg / kg /bw day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

read across to Sn compound with the same oxidation sztate and stability

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

pre-guideline studiy similar the later OECD 408

Deviations:

not applicable

Principles of method if other than guideline:

SNO2 was 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:

not specified

Remarks:

pre-glp

Limit test:

no

Species:

cat

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

Details on route of administration:

0.0 (control), 0.03, 0.10, 0.30 and 1.00 % for 90 days.

Vehicle:

other: in diet

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

4 wks

Frequency of treatment:

with diet

Dose / conc.:

0 other: % in diet

Dose / conc.:

0.03 other: % in diet

Dose / conc.:

0.1 other: % in diet

Dose / conc.:

0.3 other: % in diet

Dose / conc.:

1 other: % in diet

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:

.a.

Statistics:

n.a.

Clinical signs:

no effects observed

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:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Immunological findings:

no effects observed

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

Other effects:

no effects observed

Details on results:

no effects in stannix oxide groups reported

Key result

Dose descriptor:

NOAEL

Effect level:

> 100 000 ppm

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Conclusions:

NOAEL for Sn= = 100000 ppm

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

723.09 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available