title: Risk Assessment Study of Fluoride Salts: Probability-Impact Matrix of Renal and Hepatic Toxicity Markers.
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.
authors.affiliation: Department of Hygiene and Public Health, Division of Preventive and Social Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki City, Osaka, 569-8686, Japan. hyg032@osaka-med.ac.jp.
authors.forename: Kan
authors.initials: K
authors.lastname: Usuda
authors.affiliation: Department of Dentistry and Oral Surgery, Division of Medicine for Function and Morphology of Sensory Organs, Faculty of Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki City, Osaka, 569-8686, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ueno
authors.affiliation: Department of Dentistry and Oral Surgery, Division of Medicine for Function and Morphology of Sensory Organs, Faculty of Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki City, Osaka, 569-8686, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Faculty of Nursing, Osaka Medical College, 7-6, Hatchonishimachi, Takatsuki City, Osaka, 569-0095, Japan.
authors.forename: Tomotaro
authors.initials: T
authors.lastname: Dote
authors.affiliation: Faculty of Nursing, Osaka Medical College, 7-6, Hatchonishimachi, Takatsuki City, Osaka, 569-0095, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Kansai Technical Center for Occupational Medicine, 2-1-12, Tokiwacho, Chuo-ku, Osaka City, Osaka, 540-0028, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kono
authors.affiliation: Department of Hygiene and Public Health, Division of Preventive and Social Medicine, Faculty of Medicine, Osaka Medical College, 2-7, Daigakumachi, Takatsuki City, Osaka, 569-8686, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tamaki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005459:Fluorides; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D005459:Fluorides
keywords: Hepatotoxicity; Nephrotoxicity; Potassium fluoride; Risk assessment; Sodium fluoride; Zinc fluoride