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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
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 - each group should preferably contain approx. 20 female animals with implantation sites at necropsy, whereas in this study only 10 - 12 pregnant females were present in the groups. - test substance should be administered until the day prior to scheduled caesarean section. In this study the dosing was stopped eleven days before caesarean section. - 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 which were 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. Salewski staining) to confirm the non-pregnant status - gravid uteri including the cervix were not weighed. - head examinations were not carried out - no data on clinical signs were 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
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reference
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:
comparable to guideline study with acceptable restrictions
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
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
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
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
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
Dose / conc.:
0 other: mg Sn / kg diet
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)
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
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:
--
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):
-
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.
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
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
-
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.
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
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
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.
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
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 - test substance should be administered until the day prior to scheduled caesarean section. In this study the dosing was stopped five days before caesarean section. - 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
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
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
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Wistar derived stock
- Age: adult
- Weight (average per dose level; day 0 of gestation; pregnant dams): control group: 241 g; 0.5 mg/kg: 234 g; 2.3 mg/kg: 339 g; 11.0 mg/kg: 242 g; 50.0 mg/kg: 237 g; positive control: 241 g
- Housing: individually housed in mesh bottom cages in temperature and humidity-controlled quarters
- Diet (ad libitum)
- Water (ad libitum): fresh tap water
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:
20 days
Dose / conc.:
0 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: 24 mated females (22 - 24 pregnant females)
Control group: 24 mated females (20 pregnant females)
Control animals:
yes, sham-exposed
Details on study design:
- Positive control: 250 mg/kg aspirin (24 mated females received the positive control; 24 females were pregnant)
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 20 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 20
- 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
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
no effects observed
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 rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal survival.
Key result
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity, no effects observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
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 rats 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.
Key result
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: teratogenicity, no effects observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
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 rats 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.
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
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 - test substance should be administered until the day prior to scheduled caesarean section. In this study the dosing was stopped four days before caesarean section. - 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 genital 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 weighted. - 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. - age and individual weight of the animals were not given - no analysis of dose administered - data on clinical signs were not provided . - data on number and percent of pre- and post-implantation losses were not given
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
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
Species:
hamster, Syrian
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS - golden hamster from an outbred strain
- Age: adult
- Weight (average per dose level; day 0 of gestation; pregnant dams): control group: 134.2 g; 0.5 mg/kg: 127.0 g; 2.3 mg/kg: 133.6 g; 11.0 mg/kg: 135.8 g; 50.0 mg/kg: 134.8 g; positive control: 134.2 g
- Housing: individually housed in mesh bottom cages in temperature and humidity-controlled quarters
- Diet (ad libitum)
- Water (ad libitum): fresh tap water
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 mature males
- M/F ratio per cage: 1 male / 1 female
- Proof of pregnancy: appearance of motile sperm in vaginal smear referred to as day 0 of gestation
Duration of treatment / exposure:
Day 6 through Day 10 of gestation
Frequency of treatment:
daily
Duration of test:
14 days
No. of animals per sex per dose:
Treatment groups: 22 mated females (20 - 21 pregnant females)
Control group: 22 mated females (21 pregnant females)
Control animals:
yes, sham-exposed
Details on study design:
- Positive control: 250 mg/kg aspirin (22 mated females received the positive control; 22 females were pregnant)
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: appearance and behaviour with particular attention to food consumption

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 8, 10, and 14 of gestation period

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 14
- Organs examined: genital 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 per litter
- Skeletal examinations: Yes, two-thirds per litter
- Head examinations: No data
Statistics:
no data
Indices:
no data
Historical control data:
no data
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 hamster for 5 consecutive days had no clearly discernible effect on nidation or on maternal survival.
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 31 mg/kg bw/day (nominal)
Based on:
element
Remarks:
tin, recalculated from the value of tin chloride
Basis for effect level:
other: maternal toxicity
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 hamster for 5 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.
Dose descriptor:
NOAEL
Effect level:
> 50 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
> 31 mg/kg bw/day (nominal)
Based on:
element
Remarks:
tin, recalculated from the value of tin chloride
Basis for effect level:
other: teratogenicity
Abnormalities:
not specified
Developmental effects observed:
not specified
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 hamster for 5 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.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1974
Report date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
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

Constituent 1
Chemical structure
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 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:
rabbit
Strain:
other: dutch-belted
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age: adult
- Weight (average per dose level; day 0; pregnant dams): control group: 1.99 kg; 0.42 mg/kg: 2.17 kg; 1.90 mg/kg: 2.35 kg; 8.90 mg/kg: 2.27 kg; 41.5 mg/kg: 2.42 kg: positive control: 2.39 kg
- Housing: individually housed in mesh bottom 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.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Details on mating procedure:
- Impregnation procedure: artificial insemination
On Day 0, each doe was given an injection of 0.4 mL of human chorionic gonadotropin (400 IU) via the marginal ear vein. Three hours later, each doe was inseminated artificially with 0.3 mL of diluted semen from a proven donor buck using approximately 20 x 10^6 motile sperm according to the procedure described by Vogin et al (Pharmacologist 11, 282 (1969)).
Duration of treatment / exposure:
Day 6 through Day 18
Frequency of treatment:
daily
Duration of test:
29 days
No. of animals per sex per dose:
Treatment groups: 15 - 17 mated females (11 - 12 pregnant females)
Control group: 14 mated females (10 pregnant females)
Control animals:
yes, concurrent vehicle
Details on study design:
- Positive control: 2.5 mg/kg 6-aminonicotinamide dosed on Day 9 (17 mated females received the positive control; 12 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, 12, 18, and 29 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 29
- 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)
The live foetuses of each litter were then placed in an incubator for 24 hours for the evaluation of neonatal survival. All surviving pups were sacrificed, and all pups were further examined as follows:
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- 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 41.5 mg/kg bw of the test material to pregnant rabbits for 13 consecutive days had no clearly discernible effect on nidation or on maternal survival.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 41.5 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 26 mg/kg bw/day (nominal)
Based on:
element
Remarks:
tin, recalculated from the value of tin chloride
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The administration of up to 41.5 mg/kg bw of the test material to pregnant rabbits for 13 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)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 41.5 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
> 26 mg/kg bw/day (nominal)
Based on:
element
Remarks:
tin, recalculated from the value of tin chloride
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) > 41.5 mg/kg bw (nominal concentration)
NOAEL (teratogenicity) > 41.5 mg/kg bw (nominal concentration)
The administration of up to 41.5 mg/kg bw of the test material to pregnant rabbits for 13 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.