Toxicokinetics and metabolism deteriorated by acute nephrotoxicity after a single intravenous injection of hydrofluoric acid in rats.

Objectives: This study was designed to investigate the early dynamic state of hydrofluoric acid (HFA) in blood and urine as a model of accidental occupational exposure to a subtoxic dose of HFA. It was also aimed at determining the relationship between the kinetics and harmful effects of HFA on the kidney.

Methods: Rats received a single intravenous injection of HFA (3.2, 6.4, or 9.6 (LD(5)) mg/kg) or saline. The volume of each injection was 1 ml and the concentrations of HFA were 0.1, 0.2, and 0.3%, respectively. Ionized fluoride (F) was measured for the biological monitoring of HFA. Serum F concentrations were determined at 0, 5, 10, 30, 60, 120, and 300 min. Pharmacokinetic parameters were calculated with two-compartment modeling. Urine was directly collected from bladder for 300 min to determine the extent of the renal damage.

Results: AUC(0→300) values were significantly higher in the 9.6 mg/kg group than in the 3.2 and 6.4 groups. The total body clearance, V(1), V(2) and V(ss) were significantly lower in the 6.4 and 9.6 mg/kg groups than in the 3.2 mg/kg group. These results indicate that HFA was retained in blood. This could be a result of renal dysfunction. NAG/Cr and glucose excretion amount in urine were increased, and the clearance rate of F, urine volume and excretion amounts of electrolytes were decreased in the 9.6 mg/kg group compared with the saline group. These findings indicate renal tubular damage and a decrease in the amount of excretion of HFA from the kidney.

Conclusions: We consider that acute nephrotoxicity of HFA caused renal injury, and the harmful effects of HFA were subsequently aggravated by its delayed metabolism.