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Toxicological information

Repeated dose toxicity: oral

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Administrative data

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:
other: Pre-chronic study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: NTP protocol
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Tin Dichloride [CAS No. 7772-99-8]; anhydrous, food grade ~98.5% purity, source: M&T Chemicals, Inc.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Frederick Cancer Research Center, Frederick, Maryland
- Age at study initiation: 4 weeks
- Weight at study initiation: male: 84.3 to 90.4 g; female: 77.3 to 85.4 g
- Housing: 5/polycarbonate cage covered with disposable filters
- Diet (e.g. ad libitum): ad libitum; Wayne Lab Blox meal
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10 days

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily, continuous in diet
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
500, 1000, 1900, 3800, or 7500 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
48, 94, 187, 360, 887 mg/kg bw/day
Basis:
other: actual ingested males
Remarks:
Doses / Concentrations:
46, 98, 187, 376, 863 mg/kg bw/day
Basis:
other: actual ingested females
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
Animals were checked for mortality and signs of moribundity twice daily. Each animal was given a clinical examination weekly, including palpation for tissue masses or swelling. Body weight and feed consumption data were recorded weekly.
Sacrifice and pathology:
Those animals that were judged moribund were killed and necropsied. At the end of the 13-week study, all survivors and all animals found dead, unless precluded in whole or in part by autolysis or cannibalism, were necropsied.

Examinations performed in the control and high dose groups included:  gross lesions, tissue masses, abnormal lymph nodes, skin, mandibular  lymph nodes, mammary gland, salivary gland, thigh muscle, bone marrow,  thymus, trachea, lungs and bronchi, heart, thyroid, parathyroid,  esophagus, stomach, duodenum, jejunum, ileum, colon, mesenteric lymph  nodes, liver, pancreas, spleen, kidneys, adrenals, bladder, seminal  vesicles/prostate/testes or ovaries/uterus, brain, and pituitary.

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):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
There were no mortalities during the 13-week study period.  

Mean body  weight gain was reduced more than 10% in animals receiving the 7500 ppm diet, relative to control animals.  However, average daily feed  consumption at 7500 ppm was higher than that of the control group.

Seventy-100% of rats receiving the 3800 or 7500 ppm diets had gross distention  of the cecum and reddened gastric mucosa, although no compound-related  histopathologic effects were observed in the cecum, stomach, or any other  tissues examined.

Effect levels

open allclose all
Dose descriptor:
NOEL
Effect level:
187 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: gross pathology stomach and caecum
Dose descriptor:
NOEL
Effect level:
1 900 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: gross pathology stomach and caecum

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Based on the results of the 13-week study, doses of 1000 and 2000 ppm  stannous chloride in feed were selected for the chronic, 105-week study.

Applicant's summary and conclusion

Conclusions:
In a 13-week repeated dose study with F344/N rats, 70-100% of rats receiving the 3800 or 7500 ppm diets had gross distention  of the cecum and reddened gastric mucosa, although no compound-related  histopathologic effects were observed in the cecum, stomach, or any other  tissues examined. A NOEL of 1900 ppm (187 mg/kg bw/day) was determined based on the effects seen at 3800 ppm.
Based on the results of the 13-week study, doses of 1000 and 2000 ppm  stannous chloride in feed were selected for the chronic, 105-week study.

Executive summary:

A thirteen-week study was conducted to evaluate the cumulative toxicity of stannous chloride and to determine the concentrations of stannous chloride to be used in chronic studies. Male and female F344/N rats were fed diets containing 0, 500, 1000, 1900, 3800 or 7500 ppm. Seventy to 100% of rats receiving the 3800 or 7500 ppm diets had gross distention  of the cecum and reddened gastric mucosa, although no compound-related  histopathologic effects were observed in the cecum, stomach, or any other  tissues examined. A NOEL of 1900 ppm (187 mg/kg bw/day) was determined based on the effects seen at 3800 ppm.

Based on the results of the 13-week study, doses of 1000 and 2000 ppm  stannous chloride in feed were selected for the chronic, 105-week study.