Registration Dossier

Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study according guideline, glp, study from US authorities

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Reference Type:
publication
Title:
Health effects assessment for tin and tin compounds
Author:
U.S. EPA
Year:
1987
Bibliographic source:
EPA/600/8-88/055
Reference Type:
publication
Title:
Begruendungen zu Zinn(II)-Verbindnungen, anorganische in TRGS 900
Author:
Bundesanstalt für Arbeitsschutz und Arbeitsmedizin
Year:
2008
Bibliographic source:
Begruendungen zu Zinn(II)-Verbindnungen, anorganische in TRGS 900, Ausgabe März 2008

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
yes
Remarks:
additional analysis, see principles
Principles of method if other than guideline:
Additional chemical absorption of tin in bone, kidney and liver in the groups treated with 1 and 2 ppm stannous chloride was determined
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
other: rat, mice
Strain:
other: rat: F344/N, mice: B6C3F_1
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
105 weeks
Frequency of treatment:
in normal diet
Post exposure period:
0
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.000, 1.000 and 2.000 ppm SnCl_2
Basis:
nominal in diet
for rats
Remarks:
Doses / Concentrations:
0.000, 1.000 and 2.000 ppm SnCl_2
Basis:
nominal in diet
for mice
No. of animals per sex per dose:
rats: 10 per sex and dose
mice: 10 per sex and dose
Control animals:
yes

Results and discussion

Results of examinations

Relevance of carcinogenic effects / potential:
A carcinogenesis bioassay of stannous chloride was conducted in F344/N rats and B6C3Fl/N mice. The doses selected for the 2- year chronic study were 1,000 and 2,000 ppm stannous chloride because higher doses (3,800 ppm or more) in the 13-week study caused distention of the cecum in rats and mice and reddened gastric mucosa in rats. Mean body weight gain and feed consumption of dosed and control rats and mice were comparable in the chronic study. Survival of high-dose male rats was somewhat lower than that of the control and low-dose groups (37150, control; 39/50, low-dose; 30150, high-dose). Survival of control male mice was less (P < 0.05) than that of either dosed group (32/50, 42/50, 45/50); survival of the female mice appeared to be dose related (38/50,33/50, 28/50).
C-cell adenomas were significantly (P < 0.05) increased in low-dose male rats. C-cell carcinomas of the thyroid in male rats did not occur at a significant incidence; however, C-cell adenomas or carcinomas (combined) occurred in male rats with a significant positive trend (P = 0.027 for the life table test), and the incidence in either dosed group was significantly (P < 0.01, lowdose; P 50.05, high-dose) higher than that seen in the controls (control, 2/50, 4%; low-dose, 13/49, 27%; high-dose, 8/50, 16%). The incidence of C-cell carcinomas or the combined incidence of C-cell adenomas and carcinomas in previous control groups of male F344/N rats from this laboratory has been as high as 7% and 20%, respectively (historical incidence at this laboratory: C-cell adenomas, 24/288, 8.3%; C-cell carcinomas, 8/ 288, 2.8%; C-cell adenomas or carcinomas, 32/288, 11.1%). If the historical control rate is used as a basis of comparison, the low-dose effect remains significant (P < 0.01), but the high-dose does not. Since the incidences of these tumors in high-dose male rats were not significantly different from the historical control rate at this laboratory and since the incidence of C-cell hyperplasia in male rats (control, 1 / 50, 2%; low-dose, 1/49, 2%; high-dose, 2/50, 4%) was similar in dosed groups and controls,, the increased incidence of thyroid tumors in dosed male rats is not considered to be clearly related to administration of stannous chloride.
Adenomas of the lung in male rats occurred with a significant (P < 0.05) positive trend, but the increased incidence in the high-dose group was not significant in a direct comparison with the control group (controls, 0/50,0%; low-dose, 0150, 0%; high-dose, 3/50, 6%). The historical incidence of control F344/N male rats with adenomas
of the lung at this laboratory is 2.1% (6/289) with a range of 0%-6%. The incidence of male rats with either adenomas or carcinomas (combined) in the lung was not statistically significant.
Retinal degeneration, found in increased incidence in high-dose male rats and in low-dose female rats, has previously been found at this laboratory to be related to proximity to the fluorescent light.
The incidence of female mice with either hepatocellular adenomas or carcinomas exhibited a significant (P < 0.05) dose-related trend (controls, 3/49, 6%; low-dose, 4/49, 8%; high-dose, 8/49, 16%). However, the incidence observed in the high-dose group falls within the historical range for female control B6C3F1 /N mice at the laboratory (4%-18%; mean, 24/297,8%), and is not statistically significant relative to the historical control rate; thus the increase is not considered to be related to administration of stannous chloride.
Histiocytic lymphomas in female mice occurred with a significant positive trend (P < 0.05). However, the incidence of histiocytic lymphomas in the female controls (O/50, 0%) is lower than the historical incidence for mice of the same sex and strain at this laboratory (9/298, 3.0%; range, 0%-6%). Furthermore, the incidence of all lymphomas or leukemias was not significantly elevated in groups of dosed female mice (control, 6/50, 12%; low-dose, 10/49,20%; high-dose, 11 /49, 22%). The incidence of lymphomas or leukemias in the dosed groups was similar to the historical incidence for control female B6C3Fl/N mice at this laboratory (67/298, 22%).
In summary, although certain tumors observed in the present study occurred at increased incidences in the dosed groups, the historical data from the laboratory suggests
these differences could be attributed to normal variations in tumor incidence and could not be unequivocally attributed to administration of stannous chloride. Nonetheless, the increases seen for C-cell tumors in male rats may have been associated with the dietary administration of stannous chloride. In other 2-year studies using Long-Evans rats and Charles River Swiss mice (see Table l), investigators concluded that stannous chloride was not a carcinogen (Kanisawa and Schroeder, 1967; Schroeder et al., 1968). These two studies were considered inadequate to evaluate the carcinogenicity of stannous chloride because the doses used were low (0.28 ppm in the diet or 5 ppm in the water) and because histopathological examination was done on a select limited number of tissues. The absorption of stannous chloride by rats and mice has been demonstrated in the current study (Table 2) and by several previous investigators (Flinn and Inouye, 1928; Kehoe et al., 1940; Schroeder and Balassa, 1967; Schroeder et al., 1968; Yamaguchi et al., 1977; Yamaguchi et al., 1980). The amount retained in various tissues is dependent on the species and dose used (Table
2). For example, F344/N rats in the present study had concentrations of tin in the kidneys that were 28 to 68 times greater than those found in the kidneys of B6C3FI/N mice administered the same doses (Table 2), but both species accumulated equivalent concentrations of tin in the bone and liver. It is known that ingestion of stannous chloride in humans and rats results in approximately 99% excretion in the feces (Flinn and Inouye, 1928; Fritsch et al., 1977); the extremely low accumulation of tin in the bone, kidney, and liver of animals in the present study is in agreement. Utilization of stannous chloride as a food preservative or exposure to tin leached from canned
foods would presumably result in equally low absorption by humans. For example, bone, kidney, and liver from adult males contained only tenths of a pg tin/g tissue Kehoe et al., 1940).

Effect levels

open allclose all
Dose descriptor:
dose level:
Effect level:
2 ppm
Sex:
male/female
Basis for effect level:
other: SnCl2 in rat: not carcinogen
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Dose descriptor:
dose level:
Effect level:
2 ppm
Sex:
male/female
Basis for effect level:
other: SnCl2 in mice: not carcinogen
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Dose descriptor:
NOEL
Effect level:
2 ppm
Sex:
male/female
Basis for effect level:
other: for rat and mouse
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Dose descriptor:
other: RfD
Effect level:
0.62 mg/kg bw/day (nominal)
Basis for effect level:
other: rat, Sn
Remarks on result:
other:
Remarks:
Effect type: other: (migrated information)
Dose descriptor:
other: CS
Effect level:
28.7
Sex:
male/female
Basis for effect level:
other: toxicity in effects in livers and kindey for rats
Remarks on result:
other: Effect type: toxicity (migrated information)

Applicant's summary and conclusion

Conclusions:
Under the conditions of this bioassay, stannous chloride was judged not to be carcinogenic for male or female F344/ N rats or
MC3FlIN mice, although C-cell tumors of the thyroid gland in male rats may have been associated with the administration of the test
chemical.