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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1972
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
Justification for type of information:
In stomach dissociation of SnSO_4 into Sn^2+ and SO_4^2-. Read across to SnCl_2. No adverse effects of the different anions. Higher amounts of chloride and sulphate anions are part of daily nutrition than in the test compounds. So Sn(II) is responsible for effects.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1972
Report Date:
1972

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
-
Deviations:
not applicable
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Dose / conc.:
0 other: mg Sn / kg diet
Remarks:
doses see free text
Dose / conc.:
0.5 other: mg Sn / kg diet
Dose / conc.:
2.3 other: mg Sn / kg diet
Dose / conc.:
11 other: mg Sn / kg diet
Dose / conc.:
50 other: mg Sn / kg diet
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

General toxicity (maternal animals)

Clinical signs:
no effects observed
Description (incidence and severity):
-
Description (incidence and severity):
-
Mortality:
no mortality observed
Description (incidence):
-
Body weight and weight changes:
no effects observed
Description (incidence and severity):
-
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
-
Food efficiency:
no effects observed
Description (incidence and severity):
-
Water consumption and compound intake (if drinking water study):
no effects observed
Description (incidence and severity):
-
Ophthalmological findings:
not specified
Description (incidence and severity):
-
Haematological findings:
not specified
Description (incidence and severity):
-
Clinical biochemistry findings:
not specified
Description (incidence and severity):
-
Urinalysis findings:
not specified
Description (incidence and severity):
-
Behaviour (functional findings):
not specified
Description (incidence and severity):
-
Immunological findings:
not specified
Description (incidence and severity):
-
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
-
Gross pathological findings:
no effects observed
Description (incidence and severity):
-
Neuropathological findings:
not specified
Description (incidence and severity):
-
Histopathological findings: non-neoplastic:
not specified
Description (incidence and severity):
-
Histopathological findings: neoplastic:
not specified
Description (incidence and severity):
-
Other effects:
no effects observed
Description (incidence and severity):
-
Details on results:
--

Maternal developmental toxicity

Number of abortions:
no effects observed
Description (incidence and severity):
-
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
-
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
-
Early or late resorptions:
no effects observed
Description (incidence and severity):
-
Dead fetuses:
no effects observed
Description (incidence and severity):
-
Changes in pregnancy duration:
no effects observed
Description (incidence and severity):
-
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): -
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
-
Other effects:
no effects observed
Description (incidence and severity):
-
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)

Key result
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: no effects
Remarks on result:
not determinable due to absence of adverse toxic effects

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
-
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): -
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
-
Changes in sex ratio:
no effects observed
Description (incidence and severity):
-
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
-
Changes in postnatal survival:
no effects observed
Description (incidence and severity):
-
External malformations:
no effects observed
Description (incidence and severity):
-
Skeletal malformations:
no effects observed
Description (incidence and severity):
-
Visceral malformations:
no effects observed
Description (incidence and severity):
-
Other effects:
no effects observed
Description (incidence and severity):
-
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)

Key result
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: teratogenicity, no effects
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Any other information on results incl. tables

-

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.
Executive summary:

-