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EC number: 234-733-4 | CAS number: 12028-48-7
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- Experiment start date (Animal Arrival) - 30 July 2015 to Completion date of experimental phase (Foetal pathology): 09 October 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- 1. HYPOTHESIS FOR THE CATEGORY APPROACH: The hypothesis is that properties are likely to be similar or follow a similar pattern because of the presence of a common metal ion, in this case tungstate.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES):
Source: Sodium Tungstate
Target: Ammonium metatungstate
3. CATEGORY APPROACH JUSTIFICATION: See Annex 3 in CSR
4. DATA MATRIX: See Annex 3 in CSR
Cross-reference
- Reason / purpose for cross-reference:
- read-across: supporting information
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 016
- Report date:
- 2016
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- ICH Harmonised Tripartite Guideline: Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility S5 (R2): finalised (Step 4) November 2005.
- Deviations:
- no
- Principles of method if other than guideline:
- ICH Harmonised Tripartite Guideline: Detection of Toxicity to Reproduction for Medicinal Products & Toxicity to Male Fertility S5 (R2): finalised (Step 4) November 2005.
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Disodium wolframate
- EC Number:
- 236-743-4
- EC Name:
- Disodium wolframate
- Cas Number:
- 13472-45-2
- Molecular formula:
- Na2O4W
- IUPAC Name:
- Disodium dioxido(dioxo)tungsten
- Test material form:
- solid: crystalline
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 1504246000
- Purity test date: 93.1%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test item will be stored at room temperature, protected from light.
- Stability under test conditions: Test item formulations at concentrations of 0.5 mg/mL to 50 mg/mL in vehicle have been shown to be stable for up to 14 days at room temperature, when stored refrigerated and when frozen (approximately -80 ºC) (Kymos Reference S15/341-KE). On this basis, formulations, including Control, were stored refrigerated prior to use.
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD (SD
- Remarks:
- Charles River (UK) Limited, Margate, Kent, CT9 4LT, England.
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, CT9 4LT, England.
- Age at study initiation: 9 to 10 weeks
- Housing: Females were housed individually in grid-floor cages over paper lined trays.
- Diet and water (eg ad libitum): A pelleted rodent diet, VRF1 (manufactured by SDS) supplied by Charles River (UK) Limited, Margate, Kent, CT9 4LT, England, and mains tap water (in bottles) will be freely available.
- Acclimation period: The animals were acclimatised within the study room for at least two days after arrival. Towards the end of this period the animals were re-examined to confirm their suitability for use.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target ranges 19 °C to 23 °C
- Humidity (%): Target ranges 40 % to 70 %,
- Air changes (per hr): Room was air-conditioned
- Photoperiod (hrs dark / hrs light): The room was illuminated by fluorescent light set to give a cycle of 12 hours light and 12 hours dark.
IN-LIFE DATES: From: To:
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The test item was formulated for dosing as a solution in the vehicle (purified water). Separate formulations were prepared for each dose level. The weighed quantity of test item was mixed in the appropriate quantity of vehicle. The formulations were prepared within the known stability period (14 days).
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Formulations for use on the first day and towards the end of dosing was analysed to determine their achieved concentrations. Vehicle (for Controls) was also be analysed on these occasions to confirm the absence of the test item. Analysis was conducted at Kymos Pharma Services using a validated method (code C003-MP0023).
- Details on mating procedure:
- The females were obtained from the supplier timed-mated and were by Day 1 to Day 4 of gestation on arrival. For mating, each female were paired with a sexually mature male of the same strain. The day on which mating is detected was designated Day 0 of gestation.
- Duration of treatment / exposure:
- Animals wiere dosed once daily, from Day 6 of gestation to Day 17 of gestation inclusive. Control animals received the vehicle only, following the same regimen as the other groups.
- Frequency of treatment:
- Animals were dosed once daily
- Duration of test:
- From Day 6 of gestation to Day 17 of gestation inclusive
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day
- Remarks:
- Vehicle control
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 80 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 160 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 20 females per group per dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The dose levels have been selected after examining existing toxicity data and on the basis of results from a preliminary dose range finding study (Sequani Study Number: OHS0004).
- Rationale for animal assignment (if not random): Allocation to groups wiere performed using a stratified randomisation procedure based on body weight ranges recorded on arrival.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
Animals will be examined twice daily for mortality and morbidity. During the treatment period each animal was routinely checked pre-dose and soon after completion of dosing. On week days, additional observations were made approximately 1 hour after dosing and approximately 4 hours after dosing or at the end of the working day (whichever is sooner).
DETAILED CLINICAL OBSERVATIONS: Yes
All animals will be examined daily for clinical signs of toxicity or changes in behaviour and appearance from the start of treatment.
BODY WEIGHT: Yes
Day 0 of gestation body weight will be recorded by the supplier. At Sequani, body weights will be recorded daily from Day 5 to 18 of gestation, inclusive, then again on Day 20 of gestation.
FOOD CONSUMPTION: Yes
The amount of food consumed by each animal will be recorded over Days 6 to 9, 9 to 12, 12 to 15, 15 to 18, and 18 to 20 of gestation.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day #: Females were killed on Day 20 of gestation
- Organs examined: The animals were weighed, the thoracic and abdominal cavities were opened by a ventral mid-line incision and the major organs were examined. Gravid uterus and placenta weights were recorded and organs or tissues showing any macroscopic abnormalities were removed and retained in fixative
- Ovaries and uterine content:
- For pregnant females the following observations will be made: 1. Number of corpora lutea 2. Number and distribution of implantations in each uterine horn, classified as early intrauterine deaths, late intrauterine deaths, dead foetuses or live foetuses 3. Gravid uterus weight 4. Placental weight
The implantations are numbered separately for the right and left horns. Numbering is sequential, commencing at the ovarian end through to the cervix. The live foetuses and their placentae will be removed and the uterus and ovaries will be retained in neutral buffered formaldehyde. Gravid uterus and placenta weights will be recorded for pregnant females killed on Day 20 of gestation only. - Fetal examinations:
- Live foetuses will be killed by rapid cooling followed by immersion in fixative. The following observations will be made for live foetuses killed on Day 20 of gestation: 1. Foetal weights; 2. Foetal sexes, and 3. Foetal abnormalities (to include external, fresh visceral, fixed visceral and/or skeletal examinations)
- Statistics:
- Comparisons: Group 1 against Groups 2, 3 and 4.
Statistical tests and parameters: Data was processed to give group mean values and standard deviations, where appropriate. Where the data allow, the following methods wiere used for statistical analysis. Depending on the nature of the data set to be analysed, appropriate tests were applied. Where parametric tests may be appropriate they preceded by a check for homogeneity of variance using the Levene test and, where available, the Shapiro-Wilks test for normality. If either of these two assumptions fails a log transformation was applied before retesting. If the transformation fails, appropriate non-parametric tests was applied.
Proportions of foetuses affected were treated as continuous nonparametric data, using one-sided step-wise Jonckheere Tests. Probability values of less than 5 % were regarded as providing sufficient evidence to reject the null hypothesis and therefore statistical significance was identified at the p<0.05 level. For illustrative purposes, significance levels of p<0.01 and p<0.001 also were noted. - Indices:
- 1) Pre-implantation loss (%) = [(no. corpora lutea – no. implantation sites)/ number of corpora lutea] x 100
2) Post-implantation loss (%) = [(no. implantation sites – no. live foetuses)/no. of implantation sites] x 100
Mean foetal body weights will be calculated separately by sex for each litter; group mean body weights will be calculated (separately by sex) from the litter means. The percentage of foetuses in each litter exhibiting each classification of abnormality was calculated; group mean percentages was calculated from the litter percentages. The percentage of male foetuses, out of the total number of foetuses, was calculated for each litter.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There was no clinical signs associated with sodium tungstate.
- Mortality:
- no mortality observed
- Description (incidence):
- There was no moratlity associated with sodium tungstate.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Females given 160 mg/kg/day gained less weight up to Day 15 of gestation but thereafter, mean . See Tables 1a, 1b and 2 on "Any other information on results incl. tables" section below.weight gain was similar to, or greater than, Controls. Whilst this initial body weight effect resulted in a statistically significantly lower body weight gain over the dosing period (p<0.05), absolute body weight on Day 20 of gestation was comparable with Controls, including that corrected for the gravid uterus weight. Body weight was unaffected in the groups given 40 or 80 mg/kg/day. See Tables 1a, 1b and 2 on "Any other information on results incl. tables" section below.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There was no effect of sodium tungstate on food intake.
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no macroscopic abnormalities associated with sodium tungstate
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
Maternal developmental toxicity
- Number of abortions:
- no effects observed
- Description (incidence and severity):
- See Table 3 on "Any other information on results incl. tables" section below.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- There was no adverse effect of sodium tungstate on the uterine/implantation data. See Tables 4a and Table 4b on "Any other information on results incl. tables" section below.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- See Table 3 on "Any other information on results incl. tables" section below.
- Early or late resorptions:
- no effects observed
- Description (incidence and severity):
- See Table 3 on "Any other information on results incl. tables" section below.
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- See Table 4b on "Any other information on results incl. tables" section below.
- Changes in pregnancy duration:
- no effects observed
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- All females were pregnant with the exception of Animal 53 given 80 mg/kg/day. There was no adverse effect of Sodium Tungstate on the uterine/implantation data. See Table 3 on "Any other information on results incl. tables" section below.
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- ca. 80 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- ca. 160 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
Maternal abnormalities
- Key result
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- No changes on group mean values of Litter weights (g) / foetal data . See Table 5 on "Any other information on results incl. tables" section below.
- Reduction in number of live offspring:
- no effects observed
- Description (incidence and severity):
- See Table 3 on "Any other information on results incl. tables" section below.
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- There was no effect of sodium tungstate on the sex ratio. See Table 5 on "Any other information on results incl. tables" section below.
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- No changes on group mean values of Litter weights (g) / foetal data . See Table 5 on "Any other information on results incl. tables" section below.
- Changes in postnatal survival:
- no effects observed
- External malformations:
- no effects observed
- Description (incidence and severity):
- See Table 6 on "Any other information on results incl. tables" section below.
- Skeletal malformations:
- effects observed, treatment-related
- Description (incidence and severity):
- The overall incidence of minor foetal abnormalities was significantly higher than Controls in litters given 160 mg/kg/day (p<0.05). This was largely attributable to an increase in the number of foetuses which showed irregular palate ridging and incomplete nasal ossification; both incidences were above the background data ranges. Foetuses from litters given 80 mg/kg/day also showed slightly higher incidences of these abnormalities, although these did not achieve statistical significance and were only marginally higher than the background data ranges.
Changes in the palate rugae seen on this study are considered likely to be related to Sodium Tungstate given the dose response and increase in litter incidence (25 foetuses from 16 litters in the group given 160 mg/kg/day compared with 7 foetuses from 6 litters in the Control group). However, in the absence of any attendant major abnormalities, or other signs of generalised disturbance in foetal development, the changes seen at the dose levels on this study are considered not adverse. In addition to the changes in the extent of nasal ossification, there was also a slight increase in the number of foetuses from litters given 160 mg/kg/day which showed the minor defects of incomplete ossification of the caudal vertebral centra and/or hyoid bone of the skull. These incidences however, were either within, or only just outside, the background data ranges. Foetuses from litters given 80 or 160 mg/kg/day also had an increase in the variant finding of ossified cervical vertebral centra. Whilst changes in the extent of ossification typically reflect a slight developmental delay, due to the propensity for repairing by postnatal skeletal remodelling, these changes are considered not adverse. See Table 6 on "Any other information on results incl. tables" section below. - Visceral malformations:
- no effects observed
- Description (incidence and severity):
- See Table 6 on "Any other information on results incl. tables" section below.
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 160 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- ca. 40 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- skeletal malformations
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 1a. Body weight gains (g) - group mean values
Sex: Female | Body Weight Gain (Day of Gestation) | ||||||
Group | 0 to 5# | 5 to 6# | 6 to 7# | 7 to 8# | 8 to 9# |
| |
Group: 1 Control 0 mg/kg/day | Mean | 22.4 I1 | 3.9 I1 | 2.0 R2 | 3.7 I1 | 4.1 I1 |
|
SD | 11.0 | 3.8 | 6.6 | 4.8 | 7.7 |
| |
N | 20 | 20 | 20 | 20 | 20 |
| |
Group: 2 Sodium Tungstate 40 mg/kg/day | Mean | 22.2 | 4.1 | 1.4 | 4.6 | 4.0 |
|
SD | 7.8 | 3.6 | 6.1 | 5.5 | 4.9 |
| |
N | 20 | 20 | 20 | 20 | 20 |
| |
Group: 3 Sodium Tungstate 80 mg/kg/day | Mean | 20.7 | 3.8 | 1.2 | 1.6 | 4.7 |
|
SD | 9.6 | 4.7 | 6.9 | 4.6 | 4.2 |
| |
N | 19 | 19 | 19 | 19 | 19 |
| |
Group: 4 Sodium Tungstate 160 mg/kg/day | Mean | 20.4 | 4.8 | 0.3 | 2.7 | 2.8 |
|
SD | 10.3 | 5.1 | 6.9 | 3.8 | 4.3 |
| |
N | 20 | 20 | 20 | 20 | 20 |
|
# [Statistically Analysed]
1 [I - Automatic Transformation: No Transformation]
2 [R - Automatic Transformation: Rank]
Table 1b. Body weight gains (g) - group mean values
Sex: Female | Body Weight Gain (Day of Gestation) | ||||||
Group | 9 to 12# | 12 to 15# | 15 to 18# | 6 to 18# | 18 to 20# |
| |
Group: 1 Control 0 mg/kg/day | Mean | 18.7 R1 | 18.4 I2 | 29.4 I2 | 76.2 I2 | 31.6 I2 |
|
SD | 7.0 | 8.1 | 12.6 | 14.1 | 8.1 |
| |
N | 20 | 20 | 20 | 20 | 20 |
| |
Group: 2 Sodium Tungstate 40 mg/kg/day | Mean | 20.5 | 18.6 | 33.8 | 82.7 | 32.9 |
|
SD | 6.0 | 6.3 | 7.0 | 10.2 | 4.7 |
| |
N | 20 | 20 | 20 | 20 | 20 |
| |
Group: 3 Sodium Tungstate 80 mg/kg/day | Mean | 18.4 | 18.2 | 32.6 | 76.8 | 36.5 |
|
SD | 5.6 | 5.6 | 7.2 | 15.8 | 7.7 |
| |
N | 19 | 19 | 19 | 19 | 19 |
| |
Group: 4 Sodium Tungstate 160 mg/kg/day | Mean | 15.4 | 15.6 | 29.9 | 66.6 W3 | 34.8 |
|
SD | 11.0 | 6.6 | 8.9 | 16.2 | 6.5 |
| |
N | 20 | 20 | 20 | 20 | 20 |
|
# [Statistically Analysed]
1 [R - Automatic Transformation: Rank]
2 [I - Automatic Transformation: No Transformation]
3 [W - Test: Williams 2 Sided p < 0.05]
Table 2. Terminal body weight (g) adjusted for gravid uterus weight (g) - group mean values
Sex: Female | Dead Body Weight | Gravid Uterus Wt | BWt Adjusted for GUWt | Adjusted BWt Gain | |
Group | # | # | # | 6 to 20# | |
Group: 1 Control 0 mg/kg/day | Mean | 349.27 I1 | 71.1 R2 | 278.17 I1 | 32.42 I1 |
SD | 30.15 | 23.0 | 17.85 | 10.75 | |
N | 20 | 20 | 20 | 20 | |
Group: 2 Sodium Tungstate 40 mg/kg/day | Mean | 359.18 | 73.4 | 285.83 | 39.03 |
SD | 25.70 | 10.9 | 17.50 | 9.25 | |
N | 20 | 20 | 20 | 20 | |
Group: 3 Sodium Tungstate 80 mg/kg/day | Mean | 357.06 | 77.4 | 279.69 | 31.12 |
SD | 32.53 | 13.9 | 24.31 | 14.85 | |
N | 19 | 19 | 19 | 19 | |
Group: 4 Sodium Tungstate 160 mg/kg/day | Mean | 346.06 | 69.3 | 276.81 | 29.71 |
SD | 31.40 | 13.0 | 26.66 | 13.77 | |
N | 20 | 20 | 20 | 20 |
# [Statistically Analysed]
1 [I - Automatic Transformation: No Transformation]
2 [R - Automatic Transformation: Rank]
Table 3. Pregnancy data - summary
Sex: Female | Group: 1 0 mg/kg/day | Group: 2 | Group: 3 | Group: 4 Sodium Tungstate | |
Group Size |
| 20 | 20 | 20 | 20 |
Not Pregnant |
| 0 | 0 | 1 | 0 |
Not Pregnant % |
| 0.0 | 0.0 | 5.0 | 0.0 |
Not Pregnant Died/Killed | Sum | 0 | 0 | 0 | 0 |
Not Pregnant Schedule Kill | Sum | 0 | 0 | 1 | 0 |
Pregnant |
| 20 | 20 | 19 | 20 |
Pregnant % |
| 100.0 | 100.0 | 95.0 | 100.0 |
Pregnant Died/Killed/Aborted | Sum | 0 | 0 | 0 | 0 |
Pregnant with Total Resorption | Sum | 0 | 0 | 0 | 0 |
Number with Live Foetuses | Sum | 20 | 20 | 19 | 20 |
Table 4a. Uterine and implantation data - group mean values
Sex: Female | Group: 1 0 mg/kg/day | Group: 2 | Group: 3 | Group: 4 Sodium Tungstate | |
Number with Foetuses |
| 20 | 20 | 19 | 20 |
Number of Corpora Lutea# | Sum | 275 R1 | 279 | 283 | 284 |
Mean | 13.8 R1 | 14.0 | 14.9 | 14.2 | |
SD | 3.7 | 2.1 | 2.8 | 2.0 | |
Number of Implantations# | Sum | 259 R1 | 270 | 268 | 265 |
Mean | 13.0 R1 | 13.5 | 14.1 | 13.3 | |
SD | 4.1 | 1.6 | 2.0 | 2.0 | |
% Pre-implantation Loss # | Mean | 6.1 R1 | 2.6 | 4.5 | 6.3 |
Number of Early Deaths | Sum | 13 | 18 | 9 | 16 |
Mean | 0.7 | 0.9 | 0.5 | 0.8 | |
SD | 1.0 | 0.7 | 0.7 | 1.1 | |
Number of Late Deaths | Sum | 0 | 0 | 0 | 0 |
Mean | 0.0 | 0.0 | 0.0 | 0.0 | |
SD | 0.0 | 0.0 | 0.0 | 0.0 |
# [Statistically Analysed]
1 [R - Automatic Transformation: Rank]
Table 4b. Uterine and implantation data - group mean values (Continued)
Sex: Female | Group: 1 0 mg/kg/day | Group: 2 | Group: 3 | Group: 4 Sodium Tungstate | |
Number of Dead Foetuses | Sum | 0 | 0 | 0 | 0 |
Mean | 0.0 | 0.0 | 0.0 | 0.0 | |
SD | 0.0 | 0.0 | 0.0 | 0.0 | |
Number of Live Foetuses# | Sum | 246 R1 | 252 | 259 | 249 |
Mean | 12.3 R1 | 12.6 | 13.6 | 12.5 | |
SD | 4.0 | 1.8 | 2.3 | 2.2 | |
% Post-implantation Loss # | Mean | 4.6 R1 | 6.8 | 3.6 | 6.1 |
Mean % of Implantations | Mean | 95.4 | 93.2 | 96.4 | 93.9 |
# [Statistically Analysed]
1 [R - Automatic Transformation: Rank]
Table 5. Litter weights (g) / foetal data - group mean values
Sex: Female | Group: 1 0 mg/kg/day | Group: 2 | Group: 3 | Group: 4 Sodium Tungstate | |
Number with Live Foetuses |
| 20 | 20 | 19 | 20 |
No of Live Foetuses | Sum | 246 | 252 | 259 | 249 |
No of Male Foetuses | Sum | 133 | 145 | 141 | 114 |
No of Female Foetuses | Sum | 113 | 107 | 118 | 135 |
% of Male Foetuses# | Mean | 56.3 I1 | 57.3 | 54.8 | 44.3 W2 |
Litter Weight (g)# | Mean | 46.66 R3 | 47.85 | 51.40 | 46.15 |
Foetal Weight (M+F) (g)# | Mean | 3.83 I1 | 3.80 | 3.77 | 3.70 |
Foetal Weight (M) (g) | Mean | 3.93 | 3.88 | 3.88 | 3.82 |
Foetal Weight (F) (g) | Mean | 3.65 | 3.68 | 3.67 | 3.60 |
Placental Weight (g)# | Mean | 0.58 R3 | 0.55 | 0.52 | 0.52 |
# [Statistically Analysed]
1 [I - Automatic Transformation: No Transformation]
2 [W - Test: Williams 2 Sided p < 0.05]
3 [R - Automatic Transformation: Rank]
Table 6. Examination of foetuses - summary of group mean values
Combined examination (external/visceral/skeletal) | Group: 1 Control 0 mg/kg/day | Group: 2 | Group: 3 | Group: 4 Sodium Tungstate |
| ||
Total number of litters examined | 20 | 20 | 19 | 20 | |||
Total number of foetuses examined | 246 | 252 | 259 | 249 | |||
Number with major abnormalities | 1 | 1 | 1 | 0 | |||
Mean % of foetuses examined | 0.4 | 0.5 | 0.5 | 0.5
| |||
Number of litters affected# | 1 | 1 | 1 | 0 | |||
Number with minor abnormalities | 56 | 74 | 75 | 81 | |||
Mean % of foetuses examined | 23.2 | 30.1 | 28.4 | 33.1 | |||
Number of litters affected | 19 | 20 | 19 | 20J | |||
Number with variations | 136 | 129 | 136 | 150 | |||
Mean % of foetuses examine | 58.1 | 51.5 | 52.4 | 60.2 | |||
Number of litters affected# | 20 | 20 | 19 | 20 |
Applicant's summary and conclusion
- Conclusions:
- Administration of sodium tungstate by oral gavage, once daily from Days 6 to 17 of gestation to Crl:CD(SD) rats at 40, 80 or 160 mg/kg/day was generally well tolerated. Maternal effects (initial body weight change) were evident at 160 mg/kg/day and minor foetal abnormalities were apparent at 80 or 160 mg/kg/day; however, these changes were considered not adverse.
- Executive summary:
No fertility, reproductive, or developmental toxicity data of sufficient quality are available for ammonium metatungstate (target substance). However, developmental toxicity data are available for sodium tungstate (source substance), which are used for read-across. Due to similar water solubility and toxicity for ammonium metatungstate (target substance) compared to sodium tungstate (source substance), the resulting read-across from the source substance to the target substance is appropriate as an reasonable estimate of potential toxicity for this endpoint. In addition, read-across is appropriate because the classification and labeling is similar for the source substance and target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, similar. For more details, refer to the read-across category approach in the Category section of this IUCLID submission or Annex 3 in the CSR.
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