Ammonium trivanadium octaoxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

poster only, no full description of methods and results

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

poster only, no full description of methods and results

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:

no guideline followed

Principles of method if other than guideline:

In this study, groups of 10 male and 10 female B6C3F1/N mice were exposed to sodium metavanadate at concentrations of 0, 31, 63, 125, 250, and 500 mg/L via drinking water for a duration of 13 weeks. The following parameters were investigated: mortality, body weight, water consumption, compound intake, haematology, and organ weights.

GLP compliance:

not specified

Remarks:

not specified in the publication

Limit test:

no

Specific details on test material used for the study:

not specified

Species:

mouse

Strain:

B6C3F1

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: drinking water

Details on route of administration:

Exposure to vanadium may occur via ingestion.

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Dose / conc.:

31 mg/L drinking water

Dose / conc.:

63 mg/L drinking water

Dose / conc.:

125 mg/L drinking water

Dose / conc.:

250 mg/L drinking water

Dose / conc.:

500 mg/L drinking water

No. of animals per sex per dose:

10 males / 10 females

Control animals:

yes

Details on study design:

- Dose selection rationale: drinking water concentrations were selected on 14-day data.

Positive control:

not specified

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: survival

DETAILED CLINICAL OBSERVATIONS: Not specified
BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE: Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE: Yes

OPHTHALMOSCOPIC EXAMINATION: Not specified
HAEMATOLOGY: Yes
CLINICAL CHEMISTRY: Not specified
URINALYSIS: Not specified
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified

Sacrifice and pathology:

ORGAN WEIGHTS: Yes
HISTOPATHOLOGY: Yes (still under evaluation)

Statistics:

mean and standard deviation

Clinical signs:

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

- one male mouse in the 500 mg/L group was removed from study in week 3, all other animals survived.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

- on day 91, male body weights were -26 % vs. controls in the 500 mg/L group, all others were within 11 % of controls; females were -23 % and -14 % vs. controls for 500 and 250 mg/L, respectively.

Please also refer to the field "Attached background material" below (Figure 7 in the attached document).

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

- there was a decrease in water consumption at 500 mg/L in males and females, resulting in less than dose proportional intake of sodium metavanadate

Please also refer to the field "Attached background material" below (Table 9 in the attached document).

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

- there was increase in erythrocytes (17 - 25 % at 500 mg/L) and reticulocytes (38 - 50 % at 500 mg/L) and small decrease in hematocrit and hemoglobin in males and females exposed to sodium metavanadate.

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:

effects observed, treatment-related

Description (incidence and severity):

- thymus weights were lower in sodium metavanadate-exposed mice; 250 mg/L (male) and 500 mg/L

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

not specified

Remarks on result:

not determinable

Critical effects observed:

not specified

Conclusions:

In this study, groups of 10 male and 10 female B6C3F1/N mice were exposed to sodium metavanadate at concentrations of 0, 31, 63, 125, 250, and 500 mg/L via drinking water for a duration of 13 weeks. Sodium metavanadate in drinking water resulted in lower body weights and water consumption at 500 mg/L in adult mice. Mice exposed to higher concentrations of sodium metavanadate also had lower thymus weight. Lastly, mice exposed to higher (125, 150, 500 mg/L) concentrations of sodium metavanadate exhibited increase in erythrocytes and reticulocytes and decreases hematocrit and hemoglobin.

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

poster only, no full description of methods and results

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:

no guideline followed

Principles of method if other than guideline:

In this study, time-mated F0 Hsd:Sprague-Dawley rats were exposed to sodium metavanadate at concentrations of 0, 31, 63, 125, 250, and 500 mg/L via drinking water beginning on gestation day 6. Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling). The following parameters were investigated: mortality, body weight, water consumption, compund intake, and analysis of vanadium in plasma and urine.

GLP compliance:

not specified

Remarks:

not specified in the publication

Limit test:

no

Specific details on test material used for the study:

not specified

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: drinking water

Details on route of administration:

Exposure to vanadium may occur via ingestion.

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

F0 group: gestation day 6 upto weaning of offspirng
F1 group: gestation day 6 upto weaning and 13- weeks post-weaning

Frequency of treatment:

daily

Dose / conc.:

31 mg/L drinking water

Dose / conc.:

63 mg/L drinking water

Dose / conc.:

125 mg/L drinking water

Dose / conc.:

250 mg/L drinking water

Dose / conc.:

500 mg/L drinking water

No. of animals per sex per dose:

F0 group: 16 females
F1 group: 15 males / 15 females

Control animals:

yes

Details on study design:

- Dose selection rationale: drinking water concentrations were selected on 14-day data.

Time-mated F0 rats were exposed to the test item via drinking water beginning on gestation day 6.
Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling).

Positive control:

not specified

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: surivival

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: gestational, lactational F0 body weights, F1 body weights

FOOD CONSUMPTION AND COMPOUND INTAKE: Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE: Yes
OPHTHALMOSCOPIC EXAMINATION: Not specified
CLINICAL PATHOLOGY: Yes (still under evaluation)
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified

OTHER:
1) Fertility, fecunditiy, pup surivival
2) measurement of vanadium concentration in plasma and urine
- at the end of the 13 week post weaning exposure period, 5 rats per sex per group, were placed in metabolism cages (24 hours) for collection of urine.
- after 24 hours, rats were euthanized and blood was collected.
- speciation of vanadium in biological fluids was not possible, thus total vanadium was measured.
- samples were thawed, processed by acid digestion with heat, spiked with internal standard (praseodymium) and diluted with DI H2O for analysis.
- samples were analysed using inductively-coupled plasma-mass spectrometry on a Thermo X-Series, ThermoFisher Scientific (Waltham, MA).

Sacrifice and pathology:

ORGAN WEIGHTS: Yes (still under evaluation)
HISTOPATHOLOGY: Yes (still under evaluation)

Statistics:

mean and standard deviation

Clinical signs:

not specified

Mortality:

mortality observed, treatment-related

Description (incidence):

- moribundity resulted in removal of F0 animals during parturition and throughout lactation in the 250 and 500 mg/L groups.
- lower pup surivival was observed in 500 mg/L pups from postnatal day 1 - 10; surivival after postnatal day 10 was similar between exposed groups and controls.

Please also refer to the field "Attached background material" below (Table 4 in the attached document).

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

- there were lower body weights in dams during gestation and lactation that was proportional to sodium metavanadate exposure.
- body weight effects were only seen in pups at 500 mg/L.
- at the end of the study for F1 pups (13-weeks post weaning), lower body weights were seen in males at ≥ 125 mg/L (-10 to -20%) and in females at 500 mg/L (-12 %).

Please also refer to the field "Attached background material" below (Figure 4 in the attached document).

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

- there was lower water consumption in the 250 and 500 mg/L groups during gestation, lactation and post-weaning for male and female F1 offspring.
- due to lower water consumption, chemical consumption in the higher groups was slightly less than dose-proportional.

Please also refer to the field "Attached background material" below (Table 5 in the attached document).

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:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

MORTALITY:
- there was no impact on surivival during gestation.
Please also refer to the field "Attached background material" below (Table 4 in the attached document).

ANALYSIS FOR TOTAL VANADIUM IN PLSMA AND URINE:
Please also refer to the field "Attached background material" below (table 7 as well as figure 5 in the attached document).

Remarks on result:

not determinable

Critical effects observed:

not specified

Conclusions:

In this study, time-mated F0 Hsd:Sprague-Dawley rats were exposed to sodium metavanadate at concentrations of 0, 31, 63, 125, 250, and 500 mg/L via drinking water beginning on gestation day 6. Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling). Dams/pups exposed to the substance at 250 and 500 mg/L in drinking water exhibited moribundity at birth, failure to thrive, and higher moribundity during lactation. Lower body weights were observed in dams during gestation and lactation, and in pups continuing until study termination. 13 weeks post-weaning.

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not specified

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

poster only, no full description of methods and results

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:

no guideline followed

Principles of method if other than guideline:

In this study, time-mated F0 Hsd:Sprague-Dawley rats were exposed to vanadyl sulfate at concentrations of 0, 21, 42, 84, 168, and 335 mg/L via drinking water beginning on gestation day 6. Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling). The following parameters were investigated: mortality, body weight, water consumption, compund intake, and analysis of vanadium in plasma and urine.

GLP compliance:

not specified

Remarks:

not specified in the publication

Limit test:

no

Specific details on test material used for the study:

not specified

Species:

rat

Strain:

Sprague-Dawley

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: drinking water

Details on route of administration:

Exposure to vanadium may occur via ingestion.

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

F0 group: gestation day 6 up to weaning of offspirng
F1 group: gestation day 6 up to weaning and 13- weeks post-weaning

Frequency of treatment:

daily

Dose / conc.:

21 mg/L drinking water

Dose / conc.:

42 mg/L drinking water

Dose / conc.:

84 mg/L drinking water

Dose / conc.:

168 mg/L drinking water

Dose / conc.:

335 mg/L drinking water

No. of animals per sex per dose:

F0 group: 16 females
F1 group: 15 males / 15 females

Control animals:

yes

Details on study design:

- Dose selection rationale: drinking water concentrations were selected on 14-day data.

Time-mated F0 rats were exposed to the test item via drinking water beginning on gestation day 6.
Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling).

Positive control:

not specified

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: surivival

DETAILED CLINICAL OBSERVATIONS: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: gestational, lactational F0 body weights, F1 body weights

FOOD CONSUMPTION AND COMPOUND INTAKE: Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE: Yes

OPHTHALMOSCOPIC EXAMINATION: Not specified

CLINICAL PATHOLOGY: Yes (still under evaluation)
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified

OTHER:
1) Fertility, fecunditiy, pup surivival
2) measurement of vanadium concentration in plasma and urine
- at the end of the 13 week post weaning exposure period, 5 rats per sex per group, were placed in metabolism cages (24 hours) for collection of urine.
- after 24 hours, rats were euthanized and blood was collected.
- speciation of vanadium in biological fluids was not possible, thus total vanadium was measured.
- samples were thawed, processed by acid digestion with heat, spiked with internal standard (praseodymium) and diluted with DI H2O for analysis.
- samples were analysed using inductively-coupled plasma-mass spectrometry on a Thermo X-Series, ThermoFisher Scientific (Waltham, MA).

Sacrifice and pathology:

ORGAN WEIGHTS: Yes (still under evaluation)
HISTOPATHOLOGY: Yes (still under evaluation)

Statistics:

mean and standard deviation

Clinical signs:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

- there was lower water consumption in the 168 and 335 mg/L groups during gestation and lactation (335 mg/L only); all others were within 10 % of controls.
- post-weaning, there was lower water consumption for F1 males ≥ 83.8 mg/L and females in the 335 mg/L group.
- due to lower water consumption, chemical consumption in the higher groups was slightly less than dose-proportional.

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:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

MORTALITY:
- there was no impact on F0 dam survival during gestation or lactation or F1 survival during lactation or post-weaning.

BODY WEIGHT AND WEIGHT CHANGES:
- there were no impacts on body weight during gestation or lactation for F0 females and no impact on F1 body weights during lactation or post-weaning.
- terminal F1 body weights were within 5 % of controls.

Please also refer to the field "Attached background material" below (Tables 2 and 3 in the attached document).

ANALYSIS FOR TOTAL VANADIUM IN PLSMA AND URINE:
Please also refer to the field "Attached background material" below (table 6 as well as figure 5 in the attached document).

Remarks on result:

not determinable

Critical effects observed:

not specified

Conclusions:

In this study, time-mated F0 Hsd:Sprague-Dawley rats were exposed to vanadyl sulfate at concentrations of 0, 21, 42, 84, 168, and 335 mg/L via drinking water beginning on gestation day 6. Groups of male and female F1 animals were exposed during gestation, lactation and 13-weeks post-weaning (5 animals for biological sampling). Vanadyl sulfate, up to 335 mg/L in drinking water, was well tolerated in time-mated rats during gestation and lactation, and their pups during lactation and up to 13-weeks post weaning.

Data source

Reference

Reference Type:

publication

Title:

3-month toxicity studies of tetravalent and pentavalent vanadium compounds in Hsd: Sprague-Dawley SD rats and B6C3F1/N mice via drinking water exposure

Author:

Roberts, G. et al.

Year:

2019

Bibliographic source:

Society of Toxicology, 2019 Annual Meeting, Abstract '2374, Poster Board #786

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

In this study, groups of 10 male and 10 female B6C3F1/N mice were exposed to vanadyl sulfate at concentrations of 0, 21, 42, 84, 168, and 335 mg/L via drinking water for a duration of 13 weeks. The following parameters were investigated: mortality, body weight, water consumption, compound intake, haematology, and organ weights.

GLP compliance:

not specified

Remarks:

not specified in the publication

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Vanadium oxide sulphate

EC Number:

248-652-7

EC Name:

Vanadium oxide sulphate

Cas Number:

27774-13-6

Molecular formula:

VOSO4

IUPAC Name:

oxovanadium(2+) sulfate

Test material form:

not specified

Details on test material:

not specified

Specific details on test material used for the study:

not specified

Test animals

Species:

mouse

Strain:

B6C3F1

Details on species / strain selection:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Administration / exposure

Route of administration:

oral: drinking water

Details on route of administration:

Exposure to vanadium may occur via ingestion.

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

21 mg/L drinking water

Doses / concentrations 2

Dose / conc.:

42 mg/L drinking water

Doses / concentrations 3

Dose / conc.:

84 mg/L drinking water

Doses / concentrations 4

Dose / conc.:

168 mg/L drinking water

Doses / concentrations 5

Dose / conc.:

335 mg/L drinking water

No. of animals per sex per dose:

10 males / 10 females

Control animals:

yes

Details on study design:

- Dose selection rationale: drinking water concentrations were selected on 14-day data.

Positive control:

not specified

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: survival

DETAILED CLINICAL OBSERVATIONS: Not specified
BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE:
Not specified
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE: Yes

OPHTHALMOSCOPIC EXAMINATION: Not specified
HAEMATOLOGY: Yes
CLINICAL CHEMISTRY: Not specified
URINALYSIS: Not specified
NEUROBEHAVIOURAL EXAMINATION: Not specified
IMMUNOLOGY: Not specified

Sacrifice and pathology:

ORGAN WEIGHTS: Yes
HISTOPATHOLOGY: Yes (still under evaluation)

Statistics:

mean and standard deviation

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

no mortality observed

Description (incidence):

- there was no impact on survival.

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

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:

no effects observed

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Details on results:

BODY WEIGHTA AND WEIGHT CHANGES:
- terminal body weights were within 11 % of controls.

Please also refer to the field "Attached background material" below (Figure 6 in the attached document).

WATER CONSUMPTION AND COMPOUND INTAKE:
- there was a slight decrease in water consumption at 335 mg/L in males; no change in females.

Please also refer to the field "Attached background material" below (table 8 in the attached document).

HAEMATOLOGY:
- there were no changes in haematology considered related to vanadyl sulfate exposure.

ORGAN WEIGHTS:
- there were no changes in organ weights considered related to vanadyl sulfate exposure.

Effect levels

Remarks on result:

not determinable

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In this study, groups of 10 male and 10 female B6C3F1/N mice were exposed to vanadyl sulfate at concentrations of 0, 21, 42, 84, 168, and 335 mg/L via drinking water for a duration of 13 weeks. Vanadyl sulfate, up to 335 mg/L in drinking water, was well tolerated in adult mice.