Risk Assessment Study of Fluoride Salts: Probability-Impact Matrix of Renal and Hepatic Toxicity Markers

• Published in: Biological trace element research Vol. 173; no. 1; pp. 154 - 160
• Main Authors: Usuda, Kan, Ueno, Takaaki, Ito, Yuichi, Dote, Tomotaro, Yokoyama, Hirotaka, Kono, Koichi, Tamaki, Junko
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2016; Springer Nature B.V
• Subjects: Animals; Bioavailability; Biochemistry; Biomarkers - metabolism; Biomedical and Life Sciences; Biotechnology; Body weight; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Distilled water; Female; Fluorides; Kidney - metabolism; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Diseases - pathology; Life Sciences; Liver - metabolism; Liver - pathology; Male; Nutrition; Oncology; Rats; Rats, Wistar; Risk Assessment; Risk factors; Rodents; Studies; Sodium fluoride; Zinc fluoride; Potassium fluoride; Hepatotoxicity; Nephrotoxicity; Risk assessment
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-016-0644-0

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 (ZnF 2 •4H 2 O) 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 LD 50 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 ZnF 2 induced renal damage as indicated by higher urinary NAG ( p  < 0.05 with ≥90th percentile of control). High doses of ZnF 2 also induced a significant Ccr decrease ( p  < 0.05 with ≤10th percentile of control). Low doses of NaF and mid-doses of ZnF 2 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.