Frits, chemicals

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-guideline experimental study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2000

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Five week old female Wistar rats were used in this balance, excretion and tissue distribution study. Two groups of seven rats (one control and one experimental) were fed either a control diet or a control plus sodium metavanadate diet (100 ppm) for 7 days.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Sodium metavanadate (V+5)
- Molecular formula (if other than submission substance): NaVO3
- Purchased from: Wako Pure Chem. Ind. Ltd. Japan

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Japan SLC Inc, Shizouka Japan
- Age at study initiation: Approx 5 weeks
- Weight at study initiation: 110 to 120 g
- Fasting period before study: none
- Housing: metabolic cages
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: Control diet

Details on exposure:

The animals were fed ad libitum the control diet with and without sodium vanadate (100ppm) for one week. The control diet was bought from Oriental Co., Japan and it had the following composition based on 100g of diet: Protein 24.6g, Fat 5.6g, Carbohydrate 52.8g, Cellulose 3.1g, Calcium 1.15g, Phosphorus 0.88g, Magnesium 0.25g, Sodium 0.26g, Potassium 0.89g, Iron 12.3mg, Vitamin B1 2.04mg, Vitamin B2 1.21mg, Vitamin B6 0.92mg, Niacin 9.68mg, Pantothenic acid 3.05mg, Folic acid 0.15mg, Choline 0.23g, Inositol 433mg, Vitamin A 1810 IU, Vitamin D3 80 IU, Vitamin E 10.4mg.

The vanadium content of the control diet was 0.32ppm.

Duration and frequency of treatment / exposure:

The duration of exposure was one week and this was done via the diet at libitum.

Doses / concentrations

Remarks:

Doses / Concentrations:
100ppm in the diet.

No. of animals per sex per dose / concentration:

Seven female Winstar rats for the control and the exposed group

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

No data

Details on study design:

No data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, liver, kidney, heart, lung, brain, thymus, spleen, muscle, intestine, stomach, femur and tibia
- Time and frequency of sampling: urine and faeces was collected daily during feeding. The other tissues / organ was collected at the end of the study.

Determination of vanadium in tissues was conducted using an atomic absorption spectrophotometer with a graphic furnace atomizer and in feces and urine directly by flameless atomich absorption spetrophotometry.

Statistics:

Values were reported as means SEM and the data were analysed using one-way ANOVA or by a Student-Newman-Keul test.

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Absorption of vanadium was calculated to be 1168 µg/kg/d (16.5%) of the total daily intake of 7060 ± 574 µg/kg/d.

Main ADME results 2

Type:

distribution

Results:

The majority of the vanadium distribution was found in the femur, tibia, kidney, spleen and intestine of the experimental group. The tibia had levels of 1.84 µg/g. In the control group the highest vanadium levels were found in the lung (0.13 µg/g).

Main ADME results 3

Type:

excretion

Results:

The percentages excreted in the urine and feces were 0.86% and 83.5% of the intake (7060 µg/kg/d) respectively.

Main ADME results 4

Type:

other: Retention

Results:

The retention was 15.7 %

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Absorption was calculated to be about 16.5%.

Details on distribution in tissues:

The highest vanadium distribution was found in the tibia (1.84 µg/g), and the lowest was found in the brain (0.13 µg/g). In the control group the highest vanadium levels were found in the lung.

Details on excretion:

The percentages excreted in the urine and faeces were 0.86% and 83.5% of the intake (7060 µg/kg/d, as vanadium) respectively.

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

The recovery of added vanadium in various tissues were from 96.7 to 109.3% with a maximum coefficient of variation of 8.6%.

Applicant's summary and conclusion

Conclusions:

The absorption of vanadium was calculated to be 1168 ± 519 µg/kg/d (16.5%) of the total daily intake of 7060 ± 574 µg/kg/d. The results also indicate that the majority of the vanadium was distributed in the femur, tibia, kidney, spleen and intestine for the experimental group. The tibia had levels of 1.84 µg/g. In the control group the highest vanadium levels were found in the lung (0.13 µg/g). Excretion levels / percentages in the urine and faeces were 0.86% and 83.5% of the intake (7060 µg/kg/d) respectively and the retention was 15.7 % of total intake.