Toxicokinetics and metabolism deteriorated by acute nephrotoxicity after a single intravenous injection of hydrofluoric acid in rats.
OBJECTIVE
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.
Mitsui
Go
G
Department of Hygiene and Public Health I · II, Osaka Medical College, 2-7 Daigakumachi, Takatsuki City, Osaka, Japan. go.mitsui-107@nifty.com
Dote
Tomotaro
T
Yamadori
Emi
E
Imanishi
Masafumi
M
Nakayama
Shin
S
Ohnishi
Keiko
K
Kono
Koichi
K
D000818:Animals; D006207:Half-Life; D006858:Hydrofluoric Acid / Q000097:blood / Q000633:toxicity* / Q000652:urine*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000652:urine*; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D006858:Hydrofluoric Acid