Tin dioxide

Toxicity to reproduction

Administrative data

Endpoint:

multi-generation reproductive toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

This information is from the Concise International Chemical Assessment Document for Tin and Inorganic Tin Compounds which was issued by World Health Organization, but no details for the test procedure. 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 didn’t 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 reproductive toxicity study is feasible.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2005

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In a multigeneration study, CPB:WU rats were given tin in the diet at 0, 200, 400, or 800 mg/kg for three generations to investigate the reproductive and developmental toxicity for Tin (as Tin(II) chloride).

GLP compliance:

not specified

Remarks:

Secondary source without such information

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tin dichloride

EC Number:

231-868-0

EC Name:

Tin dichloride

Cas Number:

7772-99-8

Molecular formula:

Cl2Sn

IUPAC Name:

tin(II) chloride

Details on test material:

No data

Test animals

Species:

rat

Strain:

other: CPB:WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

CPB:WU rats were given tin in the diet at 0, 200, 400, or 800 mg/kg for three generations.

Details on mating procedure:

No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

three generations
No detailed information for accurate exposure duration

Frequency of treatment:

no data

Details on study schedule:

No data

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Remarks:

nominal in diet

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day (nominal)

Remarks:

nominal in diet

Doses / concentrations 3

Dose / conc.:

400 mg/kg bw/day (nominal)

Remarks:

nominal in diet

Doses / concentrations 4

Dose / conc.:

800 mg/kg bw/day (nominal)

Remarks:

nominal in diet

No. of animals per sex per dose:

no data

Control animals:

yes, concurrent no treatment

Details on study design:

No data

Positive control:

no data

Examinations

Parental animals: Observations and examinations:

Yes, growth of the parents and fertility were examined during the test.

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

no data

Litter observations:

numbers of offspring per litter and birth weight were observed.

Postmortem examinations (parental animals):

no data

Postmortem examinations (offspring):

Yes, F3b and F3c generations;

Statistics:

No data

Reproductive indices:

No data

Offspring viability indices:

No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Details on results (P0)

Tin did not affect growth of the parents, fertility, numbers of offspring per litter, or birth weight.

Effect levels (P0)

Dose descriptor:

NOAEC

Effect level:

800 mg/kg diet

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Results: P1 (second parental generation)

Effect levels (P1)

Dose descriptor:

dose level:

Effect level:

625 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P1)

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

Details on results (F1)

In the study, tin did not affect numbers of offspring per litter or birth weight. Increased mortality of F2 ofspring during the first half of lactation was corrected by increasing the iron content of the mothers’ diet. Tin reduced offspring growth and haemoglobin levels during lactation but not thereafter. On pathological examination
of rats from the F3b and F3c generations, the F3b pups showed microscopic changes in the liver and spleen at weaning but not at 4 weeks of age. Within this multigeneration study, a teratogenicity tudy was carried out using 20 F2b females per dose level. On visceral and skeletal examination, there was no increase in the incidence of fetal malformations

Results: F2 generation

Effect levels (F2)

Dose descriptor:

NOAEC

Generation:

F2b

Effect level:

800 mg/kg diet

Based on:

test mat.

Sex:

female

Basis for effect level:

other: On visceral and skeletal examination, there was no increase in the incidence of foetal malformations.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

It can be concluded that, under test conditions, tIn II did not affect growth of the parents, fertility, numbers of offspring per litter, or birth weight of fetuses. Furthermore, there was no increase in the incidence of fetal malformations by test material.

Executive summary:

In a multigeneration study, CPB:WU rats were given tin in the diet at 0, 200, 400, or 800 mg/kg for three generations. To simulate the “form of the tin likely to be found in canned food,” tin(II) chloride was allowed to react in aqueous medium with the casein content of the diet. Tin did not affect growth of the parents, fertility, numbers of offspring per litter, or birth weight. Tin did not affect numbers of offspring per litter or birth weight. Increased mortality of F2 offspring during the first half of lactation was corrected by increasing the iron content of the mothers’ diet. Tin reduced offspring growth and haemoglobin levels during lactation but not thereafter. On pathological examination of rats from the F3b and F3c generations, the F3b pups showed microscopic changes in the liver and spleen at weaning but not at 4 weeks of age. Within this multigeneration study, a teratogenicity study was carried out using 20 F2b females per dose level. On visceral and skeletal examination, there was no increase in the incidence of fetal malformations.