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EC number: 231-141-8 | CAS number: 7440-31-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
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Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.31 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Tin
- EC Number:
- 231-141-8
- EC Name:
- Tin
- Cas Number:
- 7440-31-5
- Molecular formula:
- Sn
- IUPAC Name:
- tin
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Appearance: grey powder
- Storage conditions of test material: 15 to 25 °C
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Crl:WI(Han)
- Age at study initiation: Females were nine to ten weeks old
- Animal receipt: Females were delivered by Day 3 of gestation
- Weight at study initiation: Females weighed at least 140 g at mating. Females weighed between 167.3 and 252.9 g at the start of dosing.
- Fasting period before study: No
- Housing: The animals were housed singly in cages with Aspen wood chips used for bedding (changed on a weekly basis). Animals were provided with wooden Aspen chew blocks and rodent nesting materials as forms of environmental enrichment.
- Diet: Food was provided ad libitum throughout the study
- Water: Mains water was provided ad libitum via water bottles
- Acclimation period: Acclimatisation was limited by mated status
ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24 °C
- Humidity: 45 to 65 % (relative)
- Air changes: 15 to 20 per hour
- Photoperiod: 12 hrs dark / 12 hrs fluorescent light
IN-LIFE DATES
From: 03 August 2015
To: 21 August 2015
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- CMC (carboxymethyl cellulose)
- Remarks:
- 0.1 % CMC (sodium salt)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS
- Frequency of preparation: Formulations were prepared weekly
- Storage of dosing solutions: The formulations were stored refrigerated (2 to 8 °C) in a sealed container
- Test material administration: On arrival at the animal room, the formulations were stirred continuously for thirty minutes before and throughout dosing (excluding the vehicle control group).
VEHICLE
- Amount of vehicle (if gavage): A dose volume of 10 mL/kg was used. Individual dose volumes were based on individual body weight. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- STABILITY AND HOMOGENEITY
- Stability: Determined at 3 and 100 mg/mL for 14 days at 4 °C in the dark in a previous study
- Homogeneity: Determined at 3 and 100 mg/mL in a previous study
CONCENTRATION VERIFICATION
Samples were taken from formulations prepared for the first and last day of dosing. Three samples (1 mL) removed from the test material formulations were added to pre-weighed HPLC vials. These samples were analysed to determine the achieved concentration. Two samples (1 mL) were removed from the control formulations to determine the vehicle subtraction weight. - Details on mating procedure:
- - Impregnation procedure: Overnight at the supplier’s laboratory
- Proof of pregnancy: Presence of a vaginal plug in situ, or other evidence of mating, if necessary. The day on which mating was confirmed was designated as Day 0 of gestation.
- Other: Females were considered to be sexually mature at the start of dosing. - Duration of treatment / exposure:
- From Day 6 to 20 of gestation
- Frequency of treatment:
- Once daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 30 mg/kg bw/day (nominal)
- Dose / conc.:
- 300 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 20 females per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The high dose level of 1000 mg/kg/day was the No-Observed-Effect-Level (NOEL) in the rat OECD 421 screening study. In the event of treatment related effects, 300 mg/kg/day was considered to be an appropriate step between the low and high dose levels to help characterise findings. The low dose level, 30 mg/kg/day was expected to be a NOEL with respect to adult toxicity and embryo-foetal development.
- Rationale for animal assignment: The animals were assigned to treatment groups on arrival based on body weight and day of mating (i.e. all animals confirmed as mated on a specific day were randomly allocated to treatment groups).
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. The animals were observed at approximately 1 hour after dosing.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Each animal was given a detailed physical examination on the days of body weight recording. An individual record was maintained of the clinical condition of each animal.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded on Day 3, 6, 7, 8, 9, 12, 15, 17, 19, 20 and 21 of gestation.
FOOD CONSUMPTION: Yes
- Time schedule for examinations: The amount of food consumed was determined daily beginning on Day 3 of gestation. Food consumption was calculated as g/animal/day.
WATER CONSUMPTION: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #21. Females were euthanised in replicate order on Day 21 of gestation by cervical dislocation following isoflurane anaesthesia, death confirmed by exsanguination. Food was not removed prior to necropsy. All animals examined macroscopically. All lesions were recorded and retained in the relevant fixative.
- Organs examined: Ovaries and uteri - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: The number and intrauterine position of implantations was subdivided into live foetuses, early intrauterine deaths, late intrauterine deaths and dead foetuses.
Early intrauterine deaths were classified as those which showed decidua or placental tissue only. Late intrauterine deaths showed embryonic or foetal tissue in addition to placental tissue. Dead foetuses were classified as those which appeared to have died shortly before necropsy. Implantations were allocated numbers relating to their position in utero.
The uterus of any apparently non pregnant female was immersed in a 10 % ammonium sulphide solution to reveal any evidence of implantation. - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No
Live foetuses were euthanised by a subcutaneous injection of sodium pentobarbitone.
Individual foetal and placental weights were recorded and foetuses were examined externally and sexed. Approximately one half of the foetuses in each litter, selected by systematic sampling, were dissected and the visceral abnormalities were examined. They were then eviscerated and the carcasses processed for skeletal examination. The skeletons were examined in 50 % glycerol and retained in glycerol/propylene glycol.
The remaining foetuses were fixed in Bouin's fluid and examined. The foetuses fixed for visceral examination were retained in the relevant fixative.
Foetal abnormalities were classified as malformations (rare and/or potentially lethal defects) and variations (commonly occurring non-lethal abnormalities). - Statistics:
- Data from treated animals were compared with control data. Statistical analyses were performed where appropriate.
Data for each sex was analysed separately, unless stated otherwise. Except where otherwise stated, tests were performed using a two-sided risk and were considered significant where P≤0.05.
Body weight, body weight gains and food consumption were analysed using analysis of variance (ANOVA). Mean foetal weight (male, female and combined) was analysed using analysis of covariance (ANCOVA), with litter size (live and dead foetuses) as the covariate. The number of corpora lutea, implantation sites, early and late resorptions, dead foetuses, live foetuses and percent pre- and post-implantation loss and percent male foetuses were analysed using the Kruskal-Wallis and Wilcoxon rank sum test.
Gravid uterine weights and corrected body weights (carcass weights) were analysed using analysis of variance (ANOVA) and the percentage of foetuses affected (mean litter percent) was analysed using the Kruskal-Wallis and Wilcoxon rank sum test.
Proportion of litters affected was analysed using a 1–sided upper tail Fishers exact test.
Full details are given below. - Indices:
- A number of indices were used, where appropriate, to evaluate reproductive function:
- % pre-implantation loss = [(Number of corpora lutea – number of implantations) / Number of corpora lutea] x 100
- % post-implantation loss = [(Number of implantations – number of live embryos) / Number of implantations] x 100
- Carcass weight = Terminal body weight – uterus weight
- Total weight change = Day 21 body weight – Day 3 body weight
- % male foetuses = (Number of male foetuses / Number of foetuses of determined sex) x 100
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Clinical observations were consistent across groups and unaffected by treatment. Observations consisted primarily of fur and/or coat changes which are common background observations in the rat. There were no post-dosing observations associated with treatment.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no unscheduled deaths during the study.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Mean body weight parameters were unaffected by the test material at all dose levels.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption was unaffected by the test material at all dose levels.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no macroscopic observations associated with treatment. Caesarean section parameters were consistent across all dose groups and unaffected by treatment.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- DOSE ANALYSIS
The target range for the preparation of the formulations was 90 to 100 % of nominal. All results were within this range and considered acceptable for use.
Maternal developmental toxicity
- 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
- 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 - Changes in number of pregnant:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Reproductive performance was consistent across all groups and unaffected by treatment.
- Details on maternal toxic effects:
- Sixteen females with implantations per group are considered optimal for statistical analysis of data. In this study there were fifteen females with implantations in the control group. Since the study results are clear, and statistical analysis is not needed to discern the lack of effects on pregnancy and embryo-foetal development, this is not considered to have adversely affected interpretation of the study.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- External malformations:
- no effects observed
- Description (incidence and severity):
- Foetal external parameters were consistent across all groups and unaffected by treatment.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- Foetal skeletal parameters were consistent across all groups and unaffected by treatment.
- Visceral malformations:
- no effects observed
- Description (incidence and severity):
- Foetal visceral parameters were consistent across all groups and unaffected by treatment.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- 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
Table 1: Summary of Reproductive Performance
Treatment Group |
Control |
30 mg/kg |
300 mg/kg |
1000 mg/kg |
Total Females |
20 |
20 |
20 |
20 |
Pregnant Females |
15 |
17 |
17 |
19 |
Non Pregnant Females |
5 |
3 |
3 |
1 |
Pregnant with Total Litter Loss |
1 |
1 |
1 |
0 |
Females with Live Foeuses |
14 |
16 |
16 |
19 |
Table 2: Summary of Mean Caesarean Section Data
Treatment Group |
Control |
30 mg/kg |
300 mg/kg |
1000 mg/kg |
Number of females pregnant at caesarean section |
15 |
17 |
17 |
19 |
Corpora lutea |
12.6 |
12.9 |
11.8 |
12.5 |
Implantation sites |
10.2 |
11.2 |
10.9 |
11.2 |
Pre-implantation loss |
2.4 |
1.7 |
0.9 |
1.3 |
Pre-implantation loss (%) |
18.8 |
11.5 |
8.3 |
11.6 |
Early resorptions |
0.5 |
0.4 |
0.6 |
0.5 |
Late resorptions |
0.0 |
0.0 |
0.0 |
0.0 |
Total Resorptions |
0.5 |
0.4 |
0.6 |
0.5 |
Dead foetuses |
0.0 |
0.0 |
0.0 |
0.0 |
Post-implantation loss |
0.5 |
0.4 |
0.6 |
0.5 |
Post-implantation loss (%) |
11.5 |
8.7 |
10.0 |
4.1 |
Live foetuses |
10.4† |
11.5† |
10.9† |
10.8 |
†The number of females examined was reduced due to excluded data
Table 3: Summary of Mean Foetal Data
Treatment Group |
Control |
30 mg/kg |
300 mg/kg |
1000 mg/kg |
Number of females with live foetuses |
14† |
16† |
16† |
19 |
Mean number of male foetuses per litter |
4.6† |
6.2† |
5.8† |
5.5 |
Mean number of female foetuses per litter |
5.8† |
5.3† |
5.2† |
5.3 |
% Male foetuses |
48.5† |
54.1† |
53.0† |
48.1 |
Mean foetal weight (g) |
5.34† |
5.31† |
5.41† |
5.41 |
Mean¹ foetal weight - males (g) |
5.41† |
5.41† |
5.51† |
5.49 |
Mean¹ foetal weight - females (g) |
5.14† |
5.28† |
5.28† |
5.23 |
†The number of females examined was reduced due to excluded data
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, daily administration of the test material at doses up to and including 1000 mg/kg/day had no effect on parameters evaluated within this study and the No Observed Adverse Effect Level (NOAEL) is therefore concluded to be 1000 mg/kg/day for both maternal toxicity and developmental toxicity.
- Executive summary:
A pre-natal developmental toxicity study was carried out in the rat to investigate the effects of the test material on embryonic and foetal development. The study was conducted in accordance with the standardised guidelines OECD 414, EU Method B.31, US EPA OPPTS 870.3700 and JMAFF under GLP conditions.
Pregnant female Wistar rats were exposed to the test material in 0.1 % carboxymethylcellulose at dose levels of 0, 30, 300 and 1000 mg/kg/day (20 per group) on Days 6 to 20 of gestation. The females were maintained to Day 21 of gestation when they were sacrificed and their uterine contents examined.
Assessment of toxicity was based on clinical signs, body weight and food consumption. Complete necropsies were performed on all animals with a recording of macroscopic abnormalities for all tissues. Caesarean and foetal examinations were conducted.
There were no unscheduled deaths in the course of the study. Clinical observations, body weight parameters and food consumption were consistent across all groups and unaffected by treatment at doses up to 1000 mg/kg/day.
There were no macroscopic observations associated with treatment and reproductive performance was consistent across all groups and unaffected by treatment. Caesarean section parameters were consistent across all dose groups and unaffected by treatment
Foetal external, visceral and skeletal parameters were consistent across all groups and unaffected by treatment at doses up to 1000 mg/kg/day.
Under the conditions of this study, daily administration of the test material at doses up to and including 1000 mg/kg/day had no effect on parameters evaluated within this study and the No Observed Adverse Effect Level (NOAEL) is therefore concluded to be 1000 mg/kg/day for both maternal toxicity and developmental toxicity.
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