Tin dichloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Reference is considered reliable with restrictions (conduct of study prior to establishment of current test guidelines, but the conduct of the study is otherwise equivalent or similar to OECD 414 (2001)) Restrictions/deviation/deficiencies in comparison to OECD TG 414: - purity of the test substance was not stated - body weight was neither recorded on the first day of dosing nor at least every 3 days during the dosing period. - food consumption was not recorded at three-day intervals and did not coincide with days of body weight determination. Food consumption appeared to be part of the clinical observations conducted daily. - gross pathological examination of the females consisted only of the examination of the urogenital tract. - uteri of non-pregnant females were not further examined (e.g. by ammonium sulfide staining) to confirm the non-pregnant status - gravid uteri including the cervix were not weighed. - whereas commonly approximately one-half of each litter is prepared and examined for skeletal alterations and the remainder for soft tissue alterations, in this study instead one-third of each litter was prepared for soft tissue alterations and two-thirds for skeletal tissue alterations. - data on clinical signs were not provided. - age and individual weight of the animals were not given - no analysis of dose administered - data on number and percent of pre- and post-implantation losses were not given

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Principles of method if other than guideline:

Conduct of study prior to establishment of current test guidelines, but the conduct of the study is otherwise equivalent or similar to OECD 414 (2001). For details on deviations/deficiencies see technical dossier.

GLP compliance:

not specified

Remarks:

GLP was not compulsory at time of study conduct

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:

[Cl-].[Cl-].[Sn++]

IUPAC Name:

tin dichloride

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): FDA 71-33 (Stannous chloride)
- Physical state: white crystalline material

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age: adult
- Weight (average per dose level; day 0 of gestation; pregnant dams): control group: 31.1 g; 0.5 mg/kg: 30.5 g; 2.3 mg/kg: 32.3 g; 11.0 mg/kg: 33.1 g; 50.0 mg/kg: 30.7 g: positive control: 33.1 g
- Housing: individually housed in disposable plastic cages in temperature and humidity-controlled quarters
- Diet (ad libitum)
- Water (ad libitum): fresh tap water

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Test substance was administered as a water solution; 1.0 mL/kg bw

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused: females were mated with young adult males
- Proof of pregnancy: vaginal sperm plug referred to as day 0 of gestation

Duration of treatment / exposure:

Day 6 through Day 15 of gestation

Frequency of treatment:

daily

Duration of test:

17 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0.5, 2.3, 11.0, and 50.0 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

Treatment groups: 22 - 26 mated females (20 - 23 pregnant females)
Control group: 29 mated females (21 pregnant females)

Control animals:

yes, sham-exposed

Details on study design:

- Positive control: 150 mg/kg aspirin (24 mated females received the positive control; 20 females were pregnant)

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: appearance and behaviour with particular attention to food consumption and weight

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 11, 15, and 17 of gestation

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption for each animal determined: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE: No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: urogenital tract

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantation sites: Yes
- Number of resorption sites: Yes
- Numbers of live and dead foetuses were recorded

Fetal examinations:

- External examinations: Yes, all per litter (foetal sex, body weight of live foetuses and presence of external congenital abnormalities)
- Soft tissue examinations: Yes, one-third of foetuses per litter
- Skeletal examinations: Yes, two-thirds of foetuses per litter
- Head examinations: No data

Statistics:

no data

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:no effects

Details on maternal toxic effects:
The administration of up to 50 mg/kg bw of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal survival.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

> 50 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

> 31 mg/kg bw/day (nominal)

Based on:

element

Remarks:

tin

Basis for effect level:

other: maternal toxicity

3

Basis for effect level:

other: effect type not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The administration of up to 50 mg/kg bw of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Effect level:

> 50 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: teratogenicity

2

Dose descriptor:

NOAEL

Effect level:

> 31 mg/kg bw/day (nominal)

Based on:

element

Remarks:

tin

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

NOAEL (maternal toxicity) > 50 mg/kg bw (nominal concentration)
NOAEL (teratogenicity) > 50 mg/kg bw (nominal concentration)
The administration of up to 50 mg/kg bw of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or foetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring spontaneously in the sham-treated controls.