Registration Dossier
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EC number: 215-231-4 | CAS number: 1314-35-8
- 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

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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE ANALOGUE 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: Tungsten Trioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR
4. DATA MATRIX: See Annex 1 in CSR
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- read-across: supporting information
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Well documented scientfically sound study similar to OECD guidelines with sufficient information provided on materials and methods to evaluate results. However as this study is used in the context of a read across, Klimisch 2 is assigned.
- Justification for type of information:
- REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE ANALOGUE 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: Tungsten trioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR
4. DATA MATRIX: See Annex 1 in CSR - Reason / purpose for cross-reference:
- read-across: supporting information
- 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:
- other: EPA OPPTS 870.3650 "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study
- Deviations:
- yes
- Remarks:
- The protocol was extended beyond the minimum 54 days of treatment to accomodate evaluation of the development of the offspring through postnatal day 20 as well as their dams following the last dose on day 70.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories (Wilmington, MA)
- Age at study initiation: 8 weeks
- Housing: The adults (e.g., P1) were singly housed (except during mating)
- Acclimation period: 14 days - Route of administration:
- oral: gavage
- Vehicle:
- other: deionized water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The powder readily dissolved in a deionized water (diH2O) vehicle for the concentrations used in this study at 5, 62.5 and 125 mg/mL. The solution was concentrated to administer a volume of 1 mL/kg body weight not to exceed 2 mL. Fresh solution was made daily and administered via oral gavage
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Lot/batch no. (if required): no data
- Purity: no data - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: not specified
- Length of cohabitation: 14 days
- Verification of same strain and source of both sexes: not specified
- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 70 days
- Frequency of treatment:
- Daily pre- and postnatal exposure
- Details on study schedule:
- Day 13: 24 hr usine/feces
Day 14: Mating begins
Day 28: Mating ends
Day 70: Last dosing - Dose / conc.:
- 5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 40 rats per sex per treatment group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Dosing continued for 70 days and encompassed mating following 14 days of treatment, that continued through the 14 day mating period, the 22 day gestational period, and through to postnatal day (PND)20. In order to ensure a total of 70 day exposure, adults were dosed for any additional days necessary following weaning. Prenatal pup exposure was from sodium tungstate crossing through the placenta and postnatal exposure was indirect via dams' milk. Offspring (F1 generation) were monitored until PND70. On PND1 (day of parturition=PND 0), the number of pups in each litter was recorded. Litters were culled on PND4 to eight pups, and litters were weighed. Selection of pups was pseudo-random to maintain a 4 male/4 female ratio whenever possible, and all pups remained with their biological mothers.
- Parental animals: Observations and examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Throughout the exposure period, dams and the males used for mating were observed for clinical signs of toxicity.
BODY WEIGHT: Yes
- Time schedule for examinations: Pregnant dams were weighed on gestation days (GD) 1, 10, 15 and 20, and gestational weight gain and gestation length were recorded.
Various organ tissues (heart, spleen, kidney, liver, lungs, brain, testes, ovaries, thymus, bone, gastrointestinal tract, etc,) were carefully removed and postfixed in 4% paraformaldehyde no longer than 24 h. After dehydration, tissues embedded in paraffin and 40 μm coronal sections were made on glass slides for histological evaluation using hematoxylin and eosin. - Litter observations:
- PND 0-4: SIze of Litter (#males/#females), weight of litter, and gross abnormalities
PND 4: Liiter culled to 8 pups (4 males and 4 females)
PND 5: Individual pups weight starting on PND 5 and weekly therefe - Postmortem examinations (parental animals):
- Tungsten concentrations in brain tissue were measured in adults and pups for the control and highest dose groups only. Ten male and female adults from each dose group were necropsied on the day of the last dose were necropsied on PND20 and PND70. For all necropsies, animals were anesthetized via CO2 overdose followed by exsanguination via the vena cava. Concentrations of the tungstate anion were determined using inductively coupled plasma mass spectrometry (ICP-MS).
Various organ tissues (heart, spleen, kidney, liver, lungs, brain, testes, ovaries, thymus, bone, gastrointestinal tract, etc,) were carefully removed and postfixed in 4% paraformaldehyde no longer than 24 h. After dehydration, tissues embedded in paraffin and 40 μm coronal sections were made on glass slides for histological evaluation using hematoxylin and eosin (H&E) stain. - Postmortem examinations (offspring):
- Tungsten concentrations in brain tissue were measured in pups for the control and highest dose groups only. Ten male and female adults from each dose group were necropsied on the day of the last dose were necropsied on PND20 and PND70. For all necropsies, animals were anesthetized via CO2 overdose followed by exsanguination via the vena cava. Concentrations of the tungstate anion were determined using inductively coupled plasma mass spectrometry (ICP-MS).
- Statistics:
- All statistical testing was performed using ANOVA with repeated measures factors. Tukey'svHSD analysis was used to evaluate pair-wise comparisons.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Animals were observed for clinical signs of toxicity throughout the exposure period, although none were noted. Additionally, no deaths were recorded for the adult females or males at the doses tested.
- Mortality:
- no mortality observed
- Description (incidence):
- No deaths were recorded for the adult females or males at the doses tested
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Sodium tungstate treatments did not have an effect on average gestational weight gain in adults
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Sodium tungstate treatments did not have an effect on average gestational weight gain in adults
- 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):
- effects observed, treatment-related
- Description (incidence and severity):
- 1) A significant effect of tungstate exposure on spontaneous locomotor activity was detected especially with low dose treated dams. Compared to control and the high dose treated animals, the low dose treated dams spent more time on ambulatory time and distance traveled and less time in stereotypies. On the contrary, in high dose treated dams less time resting and more time in stereotypic movements than the controls or low dose group were markedly observed. Maternal retrieval test revealed that sodium tungstate exposure to dams had no effect on latency in both treatment groups. In the dams, opposing exposure effects were observed in the low and high dose groups related to locomotor activity and exploration.
2) On PND 20, the mean tungstate ion concentrations in males and females of the 125 mg/kg/day treatment group were 0.008 ± 0.006 ppm and 0.002±0.002 ppm, respectively. No tungstate ion was detected in the males or females of the control group. Furthermore, no tungstate ion was detected in the brains of males or females in the control or high dose group on PND 70.
3) Tungstate ion concentrations in dam milk secretions measured PND10–14 were significantly greater in the 125 mg/kg/day treatment group (0.45 ± 0.007 ppm) than in the low dose group (0.021 ± 0.001 ppm) or controls (0.005±0.0 ppm). Concentrations in the low dose group did not significantly differ from controls. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination showed no severe chronic injury in the organs tested. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P0 animals of 125 mg NaW dose group.
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- - The study results indicate that a significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, particularly 125 mg dose group animals showed longer gestational period when compared to control, 5 and 62.5 mg groups, but did not have an effect on average gestational weight gain in adults and offspring.
- Tungstate ion concentrations in the male and female adult and pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control. Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Further, we also observed increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated adult and pups. - Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Daily administration of sodium tungstate produced no overt evidence of toxicity and had no apparent effect on mating success
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- histopathology: non-neoplastic
- reproductive performance
- Key result
- Dose descriptor:
- LOEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Behaviour
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- histopathology: non-neoplastic
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- System:
- cardiovascular
- Organ:
- heart
- Treatment related:
- yes
- Dose response relationship:
- no
- Relevant for humans:
- not specified
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Sodium tungstate treatments did not have an effect on average gestational weight gain in adults and offspring
- Food consumption and compound intake (if feeding study):
- not specified
- 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
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- Daily administration of sodium tungstate produced no overt evidence of toxicity on offspring physical development.
- Histopathological findings:
- no effects observed
- Description (incidence and severity):
- Daily administration of sodium tungstate produced no overt evidence of toxicity on offspring physical development and no significant test article-related lesions
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Tungstate ion concentrations in the pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control. Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Further, we also observed increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in pups.
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- For righting reflex, a significant sex effect was found on male where males were faster than females. However, there was no dose related effect on this activity (Fig. 3). Further, on ultrasonic distress vocalization test, pups showed dose-related effects during 60 s time period. The high dose treated pups exhibited more vocalization than control and 5 mg groups
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- > 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- body weight and weight gain
- gross pathology
- histopathology: non-neoplastic
- Key result
- Generation:
- F1
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- developmental neurotoxicity
- Remarks on result:
- not determinable because of methodological limitations
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- Daily administration of sodium tungstate produced no overt evidence of toxicity and had no apparent effect on mating success, and did not cause a change in gestation length and weight gain in adult females. No significant test article related histopathological findings were observed in the F1 treatment groups. The 2011 publication mentions the investigation of neurobehavioral findings only in the control, low and high dose groups but not from the mid dose (only body weight gain, tungsten organ distribution data and histopathology) for the mid dose group animals are reported. The neurobehavioral results in the 2008 publication resemble the results reported in the 2011 publication. However, the 2011 paper does not quote the 2008 publication of the same group. This causes some doubt on the study design.
- Executive summary:
No fertility, reproductive, or developmental toxicity data of sufficient quality are available for tungsten trioxide (target substance). However, reproductive toxicity data are available for sodium tungstate (source substance), which will be used for reading across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.
- Further, we also observed increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated adult rats.
- Histopathological examination showed no severe chronic injury in the organs tested.
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE ANALOGUE 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: Tungsten Trioxide
3. CATEGORY APPROACH JUSTIFICATION: See Annex 1 in CSR
4. DATA MATRIX: See Annex 1 in CSR - Reason / purpose for cross-reference:
- read-across: supporting information
- 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:
- other: EPA OPPTS 870.3650 "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study
- Deviations:
- yes
- Remarks:
- The protocol was extended beyond the minimum 54 days of treatment to accomodate evaluation of the development of the offspring through postnatal day 20 as well as their dams following the last dose on day 70.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories (Wilmington, MA)
- Age at study initiation: 8 weeks
- Housing: The adults (e.g., P1) were singly housed (except during mating)
- Acclimation period: 14 days - Route of administration:
- oral: gavage
- Vehicle:
- other: deionized water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The powder readily dissolved in a deionized water (diH2O) vehicle for the concentrations used in this study at 5 mg/mL and 125 mg/mL. The solution was concentrated to administer a volume of 1 mL/kg body weight not to exceed 2 mL. Fresh solution was made daily and administered via oral gavage
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Lot/batch no. (if required): no data
- Purity: no data - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Concentrations of the tungstate anion were determined using inductively coupled plasma mass spectrometry (ICP-MS).
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: not specified
- Length of cohabitation: 14 days
- Verification of same strain and source of both sexes: not specified
- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy - Duration of treatment / exposure:
- 70 days
- Frequency of treatment:
- daily pre- and postnatal exposure
- Dose / conc.:
- 5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 62.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 40 rats per sex per treatment group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- In order to ensure a total of 70 days exposure, adults were dosed for any additional days necessary following weaning. Prenatal pup exposure was from sodium tungstate crossing through the placenta and postnatal exposure was indirect via dams' milk.
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Throughout the exposure period, dams and the males used for mating were observed for clinical signs of toxicity.
BODY WEIGHT: Yes
- Time schedule for examinations: Pregnant dams were weighed on gestation days (GD) 1, 10, 15 and 20, and gestational weight gain and gestation length were recorded.
OTHER: N/A - Ovaries and uterine content:
- no data
- Fetal examinations:
- - External examinations: No data
- Soft tissue examinations: Yes: control and high dose pups
- Skeletal examinations: No data
- Head examinations: Yes - Statistics:
- All measures were analyzed using ANOVA. Repeated measures ANOVA were used where appropriate. All animals in the pre-weanling litter were tested for righting reflex and separation distress so the litter was used as the unit of analysis for the ANOVA. The fiducial limit was pb 0.05 and post-hoc comparisons were performed using Tukey's HSD analysis for pair-wise comparisons as appropriate.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Animals were observed for clinical signs of toxicity throughout the exposure period, although none were noted.
- Mortality:
- no mortality observed
- Description (incidence):
- No deaths were recorded for the adult females or males at the doses tested
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Sodium tungstate treatments did not have an effect on average gestational weight gain in adults.
- Food consumption and compound intake (if feeding study):
- not specified
- 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):
- effects observed, treatment-related
- Description (incidence and severity):
- A significant effect of tungstate exposure on spontaneous locomotor activity was detected especially with low dose treated dams. Compared to control and the high dose treated animals, the low dose treated dams spent more time on ambulatory time and distance traveled and less time in stereotypies. On the contrary, in high dose treated dams less time resting and more time in stereotypic movements than the controls or low dose group were markedly observed.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination showed no severe chronic injury in the organs tested. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P0 animals of 125 mg dose group
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Tungstate ion concentrations in the male and female adult and pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control (data not shown). Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur
bone and gastrointestinal regions in both male and female treated adult. - Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- effects observed, treatment-related
- Description (incidence and severity):
- The study results indicate that a significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, particularly 125 mg dose group animals showed longer gestational period when compared to control, 5 and 62.5 mg groups.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): The study results indicate that a significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, particularly 125 mg dose group animals - Changes in number of pregnant:
- not specified
- Other effects:
- effects observed, treatment-related
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):
Astatistically significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, average gestation duration was longer for the 125 mg/kg/day dose group than for the control and 5 mg/kg/day groups. Average gestational weight gain did not differ across treatments. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- clinical signs
- mortality
- Key result
- Dose descriptor:
- LOEL
- Remarks:
- 125 mg dose group animals showed longer gestational period when compared to control, 5 and 62.5 mg groups
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- effects on pregnancy duration
- Dose descriptor:
- LOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Abnormalities:
- effects observed, treatment-related
- 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): Sodium tungstate treatments did not have an effect on average gestational weight gain in offspring - Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- - Increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated pups
- On PND 20, the mean tungstate ion concentrations in males and females of the 125 mg/kg/day treatment group were 0.008 ± 0.006 ppm and 0.002±0.002 ppm, respectively. No tungstate ion was detected in the males or females of the control group. Furthermore, no tungstate ion was detected in the brains of males or females in the control or high dose group on PND 70. - Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
There were no differences in average number of pups born.
All pups were inspected for physical birth defects, including missing digits, however, none were found.
The high dose group demonstrated a greater number of ultrasonic distress vocalizations when separated from the dam and littermates. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- changes in litter size and weights
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- This study evaluated the reproductive, systemic and developmental effects of sodium tungstate in rats following 70 days of daily pre-and postnatal exposurevia oral gavage to 5, 62.5 and 125 mg/kg/ day through mating, gestation and weaning (PND 0–20). Daily administration of sodium tungstate produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.
- Executive summary:
No fertility, reproductive, or developmental toxicity data of sufficient quality are available for tungsten trioxide (target substance). However, developmental toxicity data are available for sodium tungstate (source substance), which will be used for reading across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.
Tungstate ion concentrations in the male and female adult and pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control. Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Further, an increased concentration of tungstate ion distribution was observed in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated adult and pups.
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- Neurobehavioral effects of sodium tungstate exposure on rats and their progeny
- Author:
- McInturf SM, Bekkedal MY, Wilfong E, Arfsten D, Gunasekar PG, Chapman GD.
- Year:
- 2 008
- Bibliographic source:
- Neurotoxicol Teratol., 30(6): 455-61
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: EPA OPPTS 870.3650 "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Study
- Deviations:
- yes
- Remarks:
- The protocol was extended beyond the minimum 54 days of treatment to accomodate evaluation of the development of the offspring through postnatal day 20 as well as their dams following the last dose on day 70.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Disodium wolframate
- EC Number:
- 236-743-4
- EC Name:
- Disodium wolframate
- Cas Number:
- 13474-45-2
- Molecular formula:
- Na2O4W
- IUPAC Name:
- Disodium dioxido(dioxo)tungsten
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): Sodium tungstate dihydrate (Reported as 10213-10-2)
- Source: Fisher Scientific
- Analytical purity: >98%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories (Wilmington, MA)
- Age at study initiation: 8 weeks
- Housing: The adults (e.g., P1) were singly housed (except during mating)
- Acclimation period: 14 days
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: deionized water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The powder readily dissolved in a deionized water (diH2O) vehicle for the concentrations used in this study at 5 mg/mL and 125 mg/mL. The solution was concentrated to administer a volume of 1 mL/kg body weight not to exceed 2 mL. Fresh solution was made daily and administered via oral gavage
VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Lot/batch no. (if required): no data
- Purity: no data - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- Concentrations of the tungstate anion were determined using inductively coupled plasma mass spectrometry (ICP-MS).
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: not specified
- Length of cohabitation: 14 days
- Verification of same strain and source of both sexes: not specified
- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy - Duration of treatment / exposure:
- 70 days
- Frequency of treatment:
- daily pre- and postnatal exposure
Doses / concentrationsopen allclose all
- Dose / conc.:
- 5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 125 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 40 rats per sex per treatment group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- In order to ensure a total of 70 days exposure, adults were dosed for any additional days necessary following weaning. Prenatal pup exposure was from sodium tungstate crossing through the placenta and postnatal exposure was indirect via dams' milk.
Examinations
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Throughout the exposure period, dams and the males used for mating were observed for clinical signs of toxicity.
BODY WEIGHT: Yes
- Time schedule for examinations: Pregnant dams were weighed on gestation days (GD) 1, 10, 15 and 20, and gestational weight gain and gestation length were recorded.
OTHER: N/A - Ovaries and uterine content:
- no data
- Fetal examinations:
- - External examinations: No data
- Soft tissue examinations: Yes: control and high dose pups
- Skeletal examinations: No data
- Head examinations: Yes - Statistics:
- All measures were analyzed using ANOVA. Repeated measures ANOVA were used where appropriate. All animals in the pre-weanling litter were tested for righting reflex and separation distress so the litter was used as the unit of analysis for the ANOVA. The fiducial limit was pb 0.05 and post-hoc comparisons were performed using Tukey's HSD analysis for pair-wise comparisons as appropriate.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- Animals were observed for clinical signs of toxicity throughout the exposure period, although none were noted.
- Mortality:
- no mortality observed
- Description (incidence):
- No deaths were recorded for the adult females or males at the doses tested
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Sodium tungstate treatments did not have an effect on average gestational weight gain in adults.
- Food consumption and compound intake (if feeding study):
- not specified
- 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):
- effects observed, treatment-related
- Description (incidence and severity):
- A significant effect of tungstate exposure on spontaneous locomotor activity was detected especially with low dose treated dams. Compared to control and the high dose treated animals, the low dose treated dams spent more time on ambulatory time and distance traveled and less time in stereotypies. On the contrary, in high dose treated dams less time resting and more time in stereotypic movements than the controls or low dose group were markedly observed.
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- effects observed, treatment-related
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination showed no severe chronic injury in the organs tested. However, the heart showed histological lesions, histiocytic inflammation from minimal to mild with cardiomyocyte degeneration and necrosis in several P0 animals of 125 mg dose group
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- Tungstate ion concentrations in the male and female adult and pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control (data not shown). Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur
bone and gastrointestinal regions in both male and female treated adult.
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- effects observed, treatment-related
- Description (incidence and severity):
- The study results indicate that a significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, particularly 125 mg dose group animals showed longer gestational period when compared to control, 5 and 62.5 mg groups.
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.DescriptionIncidenceAndSeverityEffectsOnPregnancyDuration): The study results indicate that a significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, particularly 125 mg dose group animals - Changes in number of pregnant:
- not specified
- Other effects:
- effects observed, treatment-related
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):
Astatistically significant difference was found for one of the treatment groups on measures of reproductive toxicity. In the dams, average gestation duration was longer for the 125 mg/kg/day dose group than for the control and 5 mg/kg/day groups. Average gestational weight gain did not differ across treatments.
Effect levels (maternal animals)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- clinical signs
- mortality
- Key result
- Dose descriptor:
- LOEL
- Remarks:
- 125 mg dose group animals showed longer gestational period when compared to control, 5 and 62.5 mg groups
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- effects on pregnancy duration
- Dose descriptor:
- LOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- histopathology: non-neoplastic
Maternal abnormalities
- Key result
- Abnormalities:
- effects observed, treatment-related
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): Sodium tungstate treatments did not have an effect on average gestational weight gain in offspring - Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- not specified
- Changes in postnatal survival:
- not specified
- External malformations:
- no effects observed
- Skeletal malformations:
- no effects observed
- Visceral malformations:
- no effects observed
- Other effects:
- effects observed, treatment-related
- Description (incidence and severity):
- - Increased concentration of tungstate ion distribution in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated pups
- On PND 20, the mean tungstate ion concentrations in males and females of the 125 mg/kg/day treatment group were 0.008 ± 0.006 ppm and 0.002±0.002 ppm, respectively. No tungstate ion was detected in the males or females of the control group. Furthermore, no tungstate ion was detected in the brains of males or females in the control or high dose group on PND 70. - Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
There were no differences in average number of pups born.
All pups were inspected for physical birth defects, including missing digits, however, none were found.
The high dose group demonstrated a greater number of ultrasonic distress vocalizations when separated from the dam and littermates.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- fetal/pup body weight changes
- changes in litter size and weights
Fetal abnormalities
- Key result
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Key result
- Developmental effects observed:
- no
Any other information on results incl. tables
Tungstate ion concentrations in the male and female adult and pup brains after sodium tungstate exposure were significantly greater in the high dose (125 mg) treated rats than control. Similarly, in dam milk secretions tungstate ion concentrations was significantly greater in the 125 mg treatment group than in the low dose group or controls. Further, an increased concentration of tungstate ion distribution was observed in other major organs like heart, spleen, kidney, thymus, testes, lungs, liver, femur bone and gastrointestinal regions in both male and female treated adult and pups.
Applicant's summary and conclusion
- Conclusions:
- This study evaluated the reproductive, systemic and developmental effects of sodium tungstate in rats following 70 days of daily pre-and postnatal exposurevia oral gavage to 5, 62.5 and 125 mg/kg/ day through mating, gestation and weaning (PND 0–20). Daily administration of sodium tungstate produced no overt evidence of toxicity and had no apparent effect on mating success or offspring physical development.
- Executive summary:
No fertility, reproductive, or developmental toxicity data of sufficient quality are available for tungsten trioxide (target substance). However, developmental toxicity data are available for sodium tungstate (source substance), which will be used for reading across. Due to lower water solubility and lower toxicity for the target substance compared to the source substance, the resulting read across from the source substance to the target substance is appropriate as a conservative estimate of potential toxicity for this endpoint. In addition, read across is appropriate because the classification and labelling is more protective for the source substance than the target substance, the PBT/vPvB profile is the same, and the dose descriptors are, or are expected to be, lower for the source substance. For more details, refer to the read-across category approach included in the Category section of this IUCLID submission and/or as an Annex in the CSR.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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