Calcium tin trioxide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Published literature fulfilled basically scientific principles. Various animal data on inorganic compounds indicate even lower toxicity of Tin (IV) than Tin (II) and insoluble inorganic tin than soluble inorganic tin. Both Tin (II) oxide and Tin (IV) dioxide did not induce any effect in rats in repeated dose toxicity studies. Based on above, the use of Tin (II) oxide, Tin (IV) chloride, Tin (II) fluoride and Tin (II) chloride, as well as other stannic or stannous compounds as a structural surrogate for Tin (IV) dioxide (CAS No. 18282-26-4) for pre natal toxicity study is feasible.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1971

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Sprague-Dawley rats were given diets containing tin at 125 - 625 mg/kg (SnF2, NaSn2F5, NaSn2Cl5) throughout pregnancy (to day 20) to figure out the prenatal toxicity of tin and fluorion.

GLP compliance:

no

Remarks:

Publication

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tin difluoride

EC Number:

231-999-3

EC Name:

Tin difluoride

Cas Number:

7783-47-3

Constituent 2

Reference substance name:

22578-17-2

Cas Number:

22578-17-2

IUPAC Name:

22578-17-2

Constituent 3

Reference substance name:

102696-35-5

Cas Number:

102696-35-5

IUPAC Name:

102696-35-5

Details on test material:

no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Weanling female rats of Sprague-Dawley derivation 2 were housed individually in screened-bottom galvanized cages and fed a low fluoride basal dietat libitum.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

Each salt was blended with about 50 times its weight of this starch, and micropulverized. Sodium fluoride and stannous fluoride in the proper molar ratio (1:2) and sodium pentachlorostannite, were control salts for sodium pentafluorostannite. In addition, one diet was made with added sodium chloride to control for the sodium contributed by the highest level of sodium fluoride (242 ppm sodium)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

All fluoride- and tin-containing test salts and sodium chloride were ground in a mortar and pestle and triturated in partially hydrolyzed cornstarch to ensure adequate distribution in the diets. After formulation, the diets were analyzed for fluoride and tin. The added amounts and analytical data for tin and fluoride are compared in table 1 -refer to section "Any other information on materials and methods inl.tables". Agreement between the added and analyzed fluoride levels improved as the levels of fluoride in the diets increased.
Tin levels in diets, placentas, and fetuses were determined by emission spectroscopy. Samples of diets or individual fetuses were placed in Vycor dishes, concentrated nitric acid was added, and the samples were charred. Following complete combustion of the organic material, the sample was mixed with ultra-pure graphite and lithium carbonate buffer, placed in a graphite electrode, and excited using the standard Stallwood Jet method of excitation. The lower limit of detection of the method was 0.5 ppm tin in the diets and 0.05 ppm tin in the fetuses and placentas.

Details on mating procedure:

no detailed information is available.
Mating was indicated by the detection of sperm in the daily vaginal smear.

Duration of treatment / exposure:

throughout pregnancy (From day 0 to day 20)

Frequency of treatment:

dietary every day

Duration of test:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 125, 156, 250, 312, 500, or 625 mg/kg
Basis:
nominal in diet

No. of animals per sex per dose:

groups of 9–10 female rats

Control animals:

yes, concurrent no treatment

Details on study design:

At day 20 of pregnancy, the females were decapitated and bled. The fetuses were removed, weighed and frozen individually on dry ice. Placentas were similarly collected. Implantation sites in each uterus were counted and reabsorptions calculated. The frozen samples were stored prior to analysis for tin and fluoride.

Examinations

Maternal examinations:

Food and water intakes and body weight changes were observed during test.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes / No / No data
Examinations included:
- Gravid uterus weight: yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

No. of live fetuses per litter, average fetal weight, and average placental weight were observed.

Statistics:

Statistically significant effects of test salts and test salt level were determined by two-way analysis of variance of the values for the animals in relevant groups. Duncan's multiple range test was used to determine statistically significant differences between individual means at the 95% confidence level.

Indices:

No data

Historical control data:

no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes. Remark: Less food consumed and less body weight gain

Details on maternal toxic effects:
The rats fed the highest level of sodium pentafluorostannite consumed significantly (P < 0.05) less food in the first 7 days of gestation than animals fed the lowest level of this salt. The total 20-day food intake of the rats fed the highest level of each test salt was less than that of the rats fed the lowest level. The net weight gain of the rats fed the highest level of stannous fluoride was significantly (P < 0.05) lower than that of the rats in any other group.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

625 mg/kg diet

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The greatest number of foetal resorptions was found in groups fed sodium pentafluorostannite, but the observation was not considered toxicologically significant. There were no effects on the numbers of litters, resorptions, or live fetuses per litter. Mean placental and fetal weights were also unaffected.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

From the test, it can be concluded that the stannous (Tin II) has no teratogenic effect to rats. Based on existing information, tin (IV) is of lower toxic than Tin II. Therefore the substance tin dioxide has no developmental or teratogenic concern to animals or human.

Executive summary:

When groups of 9–10 female Sprague-Dawley rats were given diets containing tin at 0, 125, 156, 250, 312, 500, or 625 mg/kg (as tin salts (SnF2, NaSn2F5, NaSn2Cl5) throughout pregnancy (to day 20). Untreated rats had foetuses containing 0.64 mg Sn/kg. Foetal tin values were found to be elevated (0.8-1.3 mg Sn/kg) when the maternal diets contained tin salts. The greatest number of foetal resorptions was found in groups fed sodium pentafluorostannite, but the observation was not considered toxicologically significant. There were no effects on the numbers of litters, resorptions, or live fetuses per litter. Mean placental and fetal weights were also unaffected (Theuer et al., 1971).