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EC number: 234-841-1 | CAS number: 12036-21-4
- 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
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- Nanomaterial pour density
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- Endpoint summary
- Stability
- Biodegradation
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- 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

Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Remarks:
- Well reported study, however, the relevance of the study is limited because only selected parameters were investigated and animals were dosed for only 4 weeks. The test material was insufficiently described, body weight data were recorded but not reported, haematology, clinical biochemistry, FOB, necropsy, ophthalmological examination, thyroid hormones, organ weights and histopathology were not conducted/evaluated, applied doses were not analytically analysed, results were reported only in figures and raw data were not provided, historical control data were not provided either.
Data source
Reference
- Reference Type:
- publication
- Title:
- Effect of vanadium on L-ascorbic acid concentration in rat tissues
- Author:
- Zaporowska, H.
- Year:
- 1 994
- Bibliographic source:
- Gen. Pharmac. Vol. 25, No. 3, pp. 467-470
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Two month old Wistar rats of both sexes received an aqueous solution of ammonium metavanadate (AMV) at a concentration of 0.01, 0.05, 0.15 and 0.30 mg V/mL (corresponding to 0.2, 1, 3 and 6 mM solution) over 4 weeks. Food and water intake was monitored daily, body weight was recorded weekly. At study termination all animals were sacrificed and liver, kidney, adrenals and spleen were isolated for L-ascorbic acid determination.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Ammonium trioxovanadate
- EC Number:
- 232-261-3
- EC Name:
- Ammonium trioxovanadate
- Cas Number:
- 7803-55-6
- Molecular formula:
- H4N.O3V
- IUPAC Name:
- ammonium trioxovanadate
- Details on test material:
- - Source: Reachim (Russia)
- Molecular formula: NH4VO3
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- albino
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Age at study start: two month
- Diet: standard granulated roden laboratory chow- LSM (CLPP, Motycz, Poland)
- Water: control group received deionized drinking water ad libitum, treatment groups received AMV containing drinking water ad libitum
- Housing: animals were individually housed in stainless steel cages under controlled conventional conditions
ENVIRONMENTAL CONDITIONS
- Temperature: 19-20 °C
- Humidity: 60±10 %
- Photoperiod: natural day-night cycle
Administration / exposure
- Route of administration:
- oral: drinking water
- Vehicle:
- other:
- Remarks:
- deionized drinking water
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 4 weeks
- Frequency of treatment:
- drinking water, ad libitum
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.01 other: mg/mL
- Remarks:
- males: 1.18±0.01 mg/kg bw/day
females: 1.50±0.23 mg/kg bw/day
(calculated based on ingested amount of AMV solution)
- Dose / conc.:
- 0.05 other: mg/mL
- Remarks:
- males: 4.93±0.15 mg/kg bw/day
females: 6.65±0.27 mg/kg bw/day
(calculated based on ingested amount of AMV solution)
- Dose / conc.:
- 0.15 other: mg/mL
- Remarks:
- males: 12.99±1.42 mg/kg bw/day
females: 13.38±1.79 mg/kg bw/day
(calculated based on ingested amount of AMV solution)
- Dose / conc.:
- 0.3 other: mg/mL
- Remarks:
- males: 22.06±1.29 mg/kg bw/day
females: 26.62±1.41 mg/kg bw/day
(calculated based on ingested amount of AMV solution)
- No. of animals per sex per dose:
- males:
group 1: 20, group 2: 15, group 3: 16, group 4: 11, group 5: 15
females:
group 1: 20, group 2: 15, group 3: 16, group 4: 13, group 5: 15 - Control animals:
- yes
- Details on study design:
- - Rationale for animal assignment: animals were randomly divided into 5 groups
- Positive control:
- no data
Examinations
- Observations and examinations performed and frequency:
- BODY WEIGHT: Yes
- Time schedule for examinations: weekly
FOOD CONSUMPTION:
- Food consumption for each animal determined:Yes
- Time schedule for examinations: daily
WATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: daily
The vanadium intake was calculated on the basis of the amount of AMV solution consumed by the rats. - Other examinations:
- Determination of L-Ascorbic acid concentration in liver, adrenals, spleen and kidney
All organs were immediately washed with ice-cold phosphate buffered saline (PBS; pH 7.4) and delicate by desiccated with lignin. Then the portions of internal organs were homogenized in ice-cold 0.25 M sucrose. The homogenates (5%; w/v) were centrifuged at 3000 x g 10 min at 4°C. In the obtained supernatant L-ascorbic acid concentration was measured according to the method of Kyaw (1978). All assays were duplicated. - Statistics:
- Student's t-test was used for statistical analysis. A value of P < 0.05 was used as the level significance. All results are presented as mean values_ SEM.
Results and discussion
Results of examinations
- Clinical signs:
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- In animals receiving as sole drinking liquid an aqueous AMV solution of 0.15 and 0.30 mg V/mL concentration, a statistically significant and dose dependent decrease of food uptake was observed as compared with the control.
For details please refer to the field "attached background material". - Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- In animals receiving as sole drinking liquid an aqueous AMV solution of 0.15 and 0.30 mg V/mL concentration, a statistically significant and dose dependent decrease of AMV solution uptake was observed as compared with the control.
For details please refer to the field "attached background material". - 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:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- Details on results:
- L-ascorbic acid concentration in tissues:
In animals of both sexes receiving as the only drinking fluid the AMV solutions, a distinct tendency of the L-ascorbic acid level to decrease was noted in the liver, kidneys, spleen and adrenals.
For details please refer to the field "attached background material".
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 0.3 other: mg/mL
- Based on:
- element
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
- Dose descriptor:
- NOEL
- Effect level:
- 22.06 mg/kg bw/day (nominal)
- Based on:
- element
- Sex:
- male
- Basis for effect level:
- other: see remarks
- Dose descriptor:
- NOEL
- Effect level:
- 26.62 mg/kg bw/day (nominal)
- Based on:
- element
- Sex:
- female
- Basis for effect level:
- other: no adverse effect observed
Applicant's summary and conclusion
- Conclusions:
- As reported in several other studies, effects on palatability of vanadium containing fluids were observed in high dose groups. Significant and dose-dependent decreases were observed in L-ascorbic acid levels in spleen, liver, adrenals and kidneys in males exposed to 0.15 and 0.30 mg V/mL and females exposed to 0.05, 0.15 and 0.3 mg V/mL. However, as the adversity of this effect remains questionable (discussed below) and no systemic toxicity was observed, this effect is not considered to be adverse and thus not taken into account for NOAEL setting. Based on this, 0.30 mg V/mL (equivalent to 22.06 mg V/kg bw/day in males and 26.62 mg V/kg bw/day in females) represents the NOEL.
This study is well reported, however, no guideline was followed and only limited parameters were analysed. Significant and dose-dependent decreases were observed in L-ascorbic acid levels in spleen, liver, adrenals and kidneys in males exposed to 0.15 and 0.30 mg V/mL and females exposed to 0.05, 0.15 and 0.3 mg V/mL. Zaporwoska et al. (1993) reported already one year before that L-ascorbic acid levels were decreased in plasma and erythrocytes in rats exposed to ammonium metavanadate. Thus, exposure to ammonium metavanadate seems to be correlated with decreased L-ascorbic acid values in different tissues and body fluids. However, as no systemic toxicity or any other effect was observed, it remains unclear whether mild to moderate L-ascorbic acid depression in tissues is or results in any adverse effects. In a publication of Chan & Reade (1996) Wistar Shionogi rats, unable to synthesize L-ascorbic acid, were supplemented with different doses of L-ascorbic acid to determine the L-ascorbic acid requirements in Wistar rats. After 26 weeks, all animals survived and showed no clinical signs of scurvy. The average weekly body weight gain was normal. A severe L-ascorbic acid deficiency would include perinasal and peri-and intra-oral haemorrhage, joint or intramuscular haemorrhage, weakened or fractured hind limbs, delayed wound healing and a failure to thrive (Clemetson, 1989). As none of these clinical signs were observed in studies reported by Zaporowska (1993, 1994) or Chan & Reade (1996), it is assumed that this mild to moderate L-ascorbic acid depression observed in this study is not an adverse effect.
Apart from that, it has been demonstrated that the toxicity of vanadium increases with its valency. Thus, compounds containing 5 -valent V, such as ammonium metavanadate, are most poisonous. It is known that 5 -valent V enters cells through anion channels, i.e. phosphate or sulfate channels. In cells, 5 -valent V is reduced to 2 -valent VO by some reducing compounds such as L-ascorbic acid and thiol-containing cysteine. Thus, the reported reduction of L-ascorbic acid in several organs and also in blood (Zaporowska et al. 1993) is most likely the result of an enhanced consumption/reduction activity of this compound. However, in contrast to humans, rodents are able to synthesize L-ascorbic acid. Thus, it can be assumed that this reduction of L-ascorbic acid will induce re-synthesis and reduction of L-ascorbic acid is an adaptive but not an adverse effect. Apart from that, it is also noteworthy that humans are not able to synthesize L-ascorbic acid. Thus, it is assumed that the protective reduction of 5 -valent V to 2 -valent VO is performed by another reducing substance and thus, it remains questionable whether a reduction of L-ascorbic acid in rats is relevant for humans.
References:
Clemetson, I.B. et al. (1975): Synthesis and some major functions of vitamin C in aniamsl. Annals of New York Academy of Science 258, 24 -46 - Executive summary:
Two-month old Wistar rats of both sexes received an aqueous solution of ammonium metavanadate (AMV) at a concentration of 0.01, 0.05, 0.15 and 0.30 mg V/mL (corresponding to 0.2, 1, 3 and 6 mM solution) over 4 weeks. Food and water intake were monitored daily, body weight was recorded weekly. At study termination all animals were sacrificed, and liver, kidney, adrenals and spleen were isolated for L-ascorbic acid determination.
According to the author the food and fluid consumption was significantly decreased in males and females exposed to 0.15 and 0.30 mg V/mL drinking water. Additionally, the L-ascorbic acid levels in liver, adrenals, spleen and kidneys were significantly and dose-dependently decreased in males and females dosed with 0.05, 0.15 and 0.30 mg V/mL drinking water.
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