Abstract
The present risk assessment study of fluoride salts was conducted by oral administration of three different doses of sodium and potassium fluorides (NaF, KF) and zinc fluoride tetrahydrate (ZnF2 •4H2O) to male Wistar rats. The rats were divided into control and nine experimental groups, to which oral injections of 0.5 mL distilled water and 0.5 mL of fluoride solutions, respectively, were given. The dosage of fluoride compounds was adjusted to contain 2.1 mg (low-dose group, LG), 4.3 mg (mid-dose group, MG), and 5.4 mg fluoride per 200 g rat body weight (high-dose group, HG) corresponding to 5, 10, and 12.5 % of LD50 values for NaF. The 24-h urine volume, N-acetyl-β-D-glucosaminidase (NAG) and creatinine clearance (Ccr) were measured as markers of possible acute renal impact. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined in serum samples as markers of acute hepatic impact. The levels of serum and urinary fluoride were determined to evaluate fluoride bioavailability. The results reveal that higher doses of NaF, KF, and ZnF2 induced renal damage as indicated by higher urinary NAG (p < 0.05 with ≥90th percentile of control). High doses of ZnF2 also induced a significant Ccr decrease (p < 0.05 with ≤10th percentile of control). Low doses of NaF and mid-doses of ZnF2 induced polyuria (p < 0.05 with ≥90th percentile of control) while medium doses of NaF and low doses of KF also induced liver damage, as indicated by a high level of AST (p < 0.05 with ≥90th percentile of control). These findings suggest that oral administration of fluoride is a potential, dose-dependent risk factor of renal tubular damage.
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Abbreviations
- LiF:
-
Lithium fluoride
- NaF:
-
Sodium fluoride
- KF:
-
Potassium fluoride
- MgF2 :
-
Magnesium fluoride
- CaF2 :
-
Calcium fluoride
- SrF2 :
-
Strontium fluoride
- BaF2 :
-
Barium fluoride
- ZnF2 :
-
Zinc fluoride tetrahydrate
- AlF3 :
-
Aluminum fluoride
- LaF3 :
-
Lanthanum fluoride
- CeF3 :
-
Cerium fluoride
- NdF3 :
-
Neodymium fluoride
- SmF3 :
-
Samarium fluoride
- GdF3 :
-
Gadolinium fluoride
- YF3 :
-
Yttrium fluoride
- YbF2 :
-
Ytterbium fluoride
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Acknowledgments
The Japan Society for the Promotion of Science supported this study through a Grant-in-Aid for Scientific Research (JSPS KAKENHI) for scientific research (C) Number 25460822.
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All animal experiments were conducted by contract with KAC Co., Ltd. (Shiga, Japan) in accordance with their Institutional Guidelines for the Care and Use of Laboratory Animals, the Japanese Government Animal Protection and Management Law (No. 105), and the Japanese Government Notification on Feeding and Safekeeping of Animals (No. 6).
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Usuda, K., Ueno, T., Ito, Y. et al. Risk Assessment Study of Fluoride Salts: Probability-Impact Matrix of Renal and Hepatic Toxicity Markers. Biol Trace Elem Res 173, 154–160 (2016). https://doi.org/10.1007/s12011-016-0644-0
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DOI: https://doi.org/10.1007/s12011-016-0644-0