Vanadyl pyrophosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant study conducted in accordance with internationally recognised test methods

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Vanadyl pyrophosphate

EC Number:

406-260-5

EC Name:

Vanadyl pyrophosphate

Cas Number:

58834-75-6

Molecular formula:

V2P2O9

IUPAC Name:

divanadium(4+) (phosphonatooxy)phosphonate dioxidandiide

Details on test material:

- Name of test material (as cited in study report): BTN/A
- Chemical name: Vanadyl pyrophosphate
- Chemical formula: (VO)2P207
- Relative molar mass: 307.8
- Physical state Fine, dark-brown powder
- Lot/batch No.:0003
- Purity: Vanadium - 30.1%, phosphorous 21.0% by weight
- Storage condition of test material: Cool, dry, well ventilated room

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK), Kent, England
- Age at study initiation: circa 5 weeks
- Weight at study initiation: Males: 104 - 145 g; females: 104 - 134 g
- Fasting period before study: circa 18 hours
- Housing: 5 animals/cage in stainless steel cages with grid floor
- Diet (e.g. ad libitum): Pelleted rodent diet, Biosure, Cambridge, Englan, ad libitum except for overnight pre-dose fast
- Water (e.g. ad libitum): Municipal tap water, ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 25 deg C
- Humidity (%): 40 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: 1990-03-27 To: 1990-05-24

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% methylcelluose in distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 73.7, 100, 135.7, 1842 and 250 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg body weight
- Justification for choice of vehicle: Commonly used vehicle for studies of this nature

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg body weight

DOSAGE PREPARATION (if unusual): Dissolution suspension in vehicle. Stability / homogeneity confirmed by analysis

Doses:

1474, 2000, 2714, 3684 and 5000 mg/kg body weight

No. of animals per sex per dose:

Five males and five females / dose group; 5 dose groups

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 5 times on day of dosing following dosing; twice daily thereafter for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight: Weekly on Days 1, 8 and 15

Statistics:

Probit analysis by the method of Finney (1952) was used to determine the acute median lethal dosage, 95% confidence interval and slope of the dose response curve for both sexes.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 036 other: mg/Kg

95% CL:

1 607 - 2 465

Remarks on result:

other: slope (degrees): 73

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

2 322 other: mg/Kg

95% CL:

1 711 - 2 934

Remarks on result:

other: Slope (degrees):66

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 171 other: mg/Kg

95% CL:

1 789 - 2 552

Remarks on result:

other: Slope (degrees): 68

Mortality:

Animals died at dosages of 1474 mg/kg and above. The deaths occurred on Days 2, 3, 4 or 6.
1474 mg/kg bw - 1/5 males and 1/5 females
2000 mg/kg bw - 2/5 males and 0/5 females
2714 mg/kg bw - 4/5 males and 5/5 females
3684 mg/kg bw - 5/5 males and 5/5 females
5000 mg/kg bw - 5/5 males and 4/5 females

Clinical signs:

other: Ante mortem signs comprised lethargy, decreased motor activity, prone posture, ataxia, muscle tremor, bradypnoea, hyperpnoea, piloerection, ungroomed appearance, pigmented staining of the snout, hunched posture, thin body conformation, diarrhoea and dark

Gross pathology:

Necropsy of the decedents revealed altered stomach, small intestine and caecum contents and areas of body staining and cannibalisation. Necropsy of the surviving animals revealed no significant macroscopic lesion.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of BTN/A following administration of a single dose to the rat is 2171 mg/kg body weight

Executive summary:

Acute oral toxicity has been investigated using OECD/EU test methods. The median lethal dose (LD50) of the substance following administration of a single oral dose to the rat is 2171 mg/kg body weight