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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Acceptable, well-documented study which meets basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Tungstate decreases weight gain and adiposity in obese rats through increased thermogenesis and lipid oxidation
Author:
Claret M, Corominola H, , Canals I Saura J, Barcelo-Batllori S, Guinovart JJ, , and Gomis R
Year:
2005
Bibliographic source:
Endocrinology 146(10):4362-4369

Materials and methods

Principles of method if other than guideline:
The study had two purposes, the first being to determine the effects of tungstate on body weight and insulin sensitivity in a rat model of diet-induced obesity and the second being to examine the molecular mechanisms underlying this action. Examinations of the underlying molecular mechanisms are not presented in this endpoint study record.
GLP compliance:
no
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium wolframate
EC Number:
236-743-4
EC Name:
Disodium wolframate
Cas Number:
13472-45-2
Molecular formula:
Na2WO4
IUPAC Name:
disodium dioxotungstenbis(olate)
Details on test material:
- Name of test material (as cited in study report): sodium tungstate, Na2WO4 x H2O
- Supplier: Carlo Erba, Milano, Italy

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Purchased from: IFFA CREDO, L'Arbesse, France
- Body weight: 220-240 g
- Housing: individual cages
- Feed: one group was fed standard chow diet (supplying 8% of calories as fat, type AO4 from Panlab, Barcelona, Spain); a second group was fed with a cafeteria diet to induce obesity (standard chow and a daily intake of cookies, liver pate, bacon, and whole-milk supplemented with 333 g/L of sucrose and 10 g/L of a mineral and vitamin complex).

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 hours light:dark
- Temperature and humidity controlled

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
other: distilled water
Details on exposure:
- After 30 d of diet, lean and obese rats were divided in treated and untreated groups.
- Treatment was carried out by giving a solution of sodium tungstate dihydrate in distilled water for 30 days ad libitum (obese rats received the cafeteria diet for an additional 30 days during this period).
- After treatment, tested the reversibility of tungstate effects by withdrawing treatment under the same dietary conditions for 35 additional days (recovery period).
- During all of the experimental period, fluid, food consumption (corrected by the amount of water lost for each item), and body weight of all rats were recorded daily.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
- Thirty days
Frequency of treatment:
- Continuous treatment
Post exposure period:
- 35 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0.3, 0.7 or 2.0 mg/L sodium tungstate dihydrate in distilled water
Basis:
nominal in water
No. of animals per sex per dose:
Obese rats treated with 0, 0.3, 0.7, or 2 mg/L W: n = 21, 9, 11, and 20, respectively. (male rats)
Lean untreated rats: n = 9 (male rats)

Examinations

Examinations:
- At the end of the treatment period, rats from each group were killed.
- Gastrocnemius muscle (gM), interscapular brown adipose tissue (iBAT), epididymal white adipose tissue (eWAT), and the liver were excised, weighed, and rapidly frozen in liquid nitrogen or fixed in 10% buffered formalin.
- All procedures were conducted in accordance with principles of laboratory animal care (European Community and local government guidelines) and approved by the Animal Research Committee of the University of Barcelona.

Results and discussion

Details on results:
- Average tungstate ingestion in the obese group: 33 ± 1, 77 ± 2 and 227 ± 9 mg/kg bw/day for the 0.3, 0.7 and 2.0 mg/mL groups, respectively.
- At all doses tested, rats did not show side effects such as diarrhea or other toxic effects.
- Obese rats treated with either 0.7 or 2.0 mg/L decreased their weight gain by 26 and 88%, respectively, compared with sex- and age-matched untreated obese rats on the cafeteria diet.
- The deceleration in body weight gain of 2 mg/mL tungstate-treated obese rats was accompanied by a significant decrease in adiposity when compared with UO rats.
- No significant changes in iBAT, gM, or liver mass were recorded at the end of treatment.
- No significant differences in femur length were observed between treated and untreated obese rats (65 ± 2 for treated vs. 68 ± 2 mm for untreated, NS), ruling out possible effects of tungstate on growth rate.
- Treatment withdrawal (recovery period) led to progressive and sustained body weight gain, indicating that tungstate does not induce a persistent state of weight loss.

Applicant's summary and conclusion

Conclusions:
Treatment of 0.7 and 2.0 mg/L sodium tungstate dihydrate via the drinking water reduced body weight gain in obese male Wistar rats compared to untreated obese rats, this effect was reversible upon elimination of treatment.