Bismuth vanadium tetraoxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bismuth vanadium tetraoxide

EC Number:

237-898-0

EC Name:

Bismuth vanadium tetraoxide

Cas Number:

14059-33-7

Molecular formula:

Bi O4 V

IUPAC Name:

vanadium(5+) bismuth(3+) tetraoxidandiide

Details on test material:

- Name of test material (as cited in study report): Bismuth Vanadate
- Molecular formula (if other than submission substance): BiVO4
- Molecular weight (if other than submission substance): 323.92
- Physical state: yellow powder
- Analytical purity: >99.5% w/w
- Impurities (identity and concentrations): water and others, <0.5% w/w
- Lot/batch No.: BVB-1018
- Stability under test conditions: stable
- Other: melting point>800°C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crj

Sex:

male/female

Details on test animals or test system and environmental conditions:

not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% arabia Gum aqueous solution

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
not reported

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

40 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

200 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

6 (12 in the control and 12 in the highest dose groups, 6 each as satellite)

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: preliminary 14-day feeding test was conducted (4 animals each sex per group receiving 50, 250 and 1000 mg/kg bw), whre the NOAEL was found to be the highest dose level tested
- Rationale for selecting satellite groups: recovery (additional control und highest dose level groups)
- Post-exposure recovery period in satellite groups: 14 days

Positive control:

not conducted

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: not reported

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at termination

BODY WEIGHT: Yes
- Time schedule for examinations: at days -3, 1, 3, 5, 8, 10 and 12

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination and at the end of the recovery period
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 6
- Parameters examined: RBC, WBC, Hb, Ht, MCV, MCHC, Platelet, reticulocytes, PT, APTTleucocytes differenciation (N-band, N-Seg, Eosino, Baso, Lymp, Mono)

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at termination and at the end of the recovery period
- Animals fasted: No data
- How many animals: 6
- Parameters examined: GOT, GPT, ALP, ChE, λ-GTP, T-Cho, TG, glucose, T-ptotein, albumin, A/G ratio, creatinine, BUN, T-Bil, Ca, IP, Na, K and Cl

URINALYSIS: Yes
- Time schedule for collection of urine: at termination and at the end of the recovery period
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters examined: volume, color, pH, protein, ketones, bilirubin, occult blood, glucose and urobilinogen

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, gross pathology/ organ weight (absolute and relative; spleen, liver, kidney, brain, testis, adrenal gland, ovary)
HISTOPATHOLOGY: Yes; skin, liver, spleen, heart, kidney, forestomach, duodenum, jejunum, ileum, cecum, colon rectum, ovary, adrenal, skin,

Other examinations:

not applicable

Statistics:

not specified

Results and discussion

Results of examinations

Description (incidence and severity):

non reversible effects: yellowish brown stool in all animals in the 200 and 1000 mg/kg group.
Reversible in the satellite group: loss of hair and exudate (neck) in one female and one male animals, respectively in the lowest and in the highest dose group; scab formation in one male animal of the highest dose level.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

no difference to the control group in all tested groups.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

no difference to the control group in all tested groups.

Description (incidence and severity):

compared to the control groups, only the diffenciation of leucocyte - N-Band (%) was higher in the highest dose level, but not different in the satellite group.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

no difference to the control group in all tested groups.

Urinalysis findings:

no effects observed

Description (incidence and severity):

no difference to the control group in all tested groups.

Description (incidence and severity):

reduced ovary weight in the highest dose of the satellite group

Description (incidence and severity):

Pelvic dilatation, blackish region of mucosa, skin exudate and scab formation were observed respectively in one female of the lowest dose group, one female of the highest dose group, one male of the lowest dose group and one female of the highest dose group. Only the blakish region of mucose was still present in 3 females of the highest dose recovery group.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Cyst formation (kidney) in one lowest dose female animal; pelvic dilatation (kidney) in one intermadiate dose male animals; necrosis mucosa (glandular stomach) in 4 (3 satellite) highest dose female animals; skin inflammation and necrosis in two animals, each one male of the lowest and highest dose group.

Effect levels

Dose descriptor:

NOEL

Effect level:

200 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: necrosis of glandular stomach, female animals of highest dose only

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The NOEL is 200 mg/kg bw/day, based on necrosis at glandular stomach observed in female animals at the highest dose group.

Applicant's summary and conclusion

Conclusions:

The NOEL is 200 mg/kg bw/day, based on necrosis at glandular stomach observed in female animals at the highest dose group.