Harmful effects and acute lethal toxicity of intravenous administration of low concentrations of hydrofluoric acid in rats

Abstract

The acute toxicity of hydrofluoric acid (HFA) was investigated in a 24-h lethal dose study of intravenous infusion in rats. The lethal dose lowest (LDLo) and LD50 were 13.1 and 17.4 mg/kg, respectively. Harmful systemic effects were also studied 1 h after acute sublethal exposure to HFA. The maximum dose was set at 9.6 mg/kg (LD5). Rats were injected with HFA (1.6, 3.2, 6.4 or 9.6 mg/kg), saline, sodium fluoride (NaF) or HCl solution. NaF and HCl solution concentrations corresponded to the F- and H+ concentrations of 9.6 mg/kg HFA. Blood urea nitrogen (BUN) and Cr were significantly increased in response to HFA concentrations greater than 3.2mg/kg. Acute glomerular dysfunction also occurred at HFA concentrations greater than 3.2 mg/kg. HCO3- and base excess (BE) were significantly decreased in the 6.4 and 9.6 mg/kg groups. Ca2+ was significantly decreased, and K+ was increased in the 9.6 mg/kg group. BUN was significantly increased in the NaF and HFA groups and was increased in the HFA group compared with that in the NaF group. Cr was significantly increased in the HFA group only. HCO3- and BE were significantly decreased in the NaF and HFA groups and were increased in the HFA group compared with values in the NaF group. Ca2+ was significantly decreased in the NaF and HFA groups, and K+ was significantly increased in the NaF and HFA groups. F- exposure directly affected serum electrolytes. Mortality was thought to be due to cardiac arrhythmia resulting from hypocalcemia and hyperkalemia. Metabolic acidosis and renal failure were more severe in response to HFA exposure than in response to NaF exposure because of more free F-, which has strong cytotoxicity, in the HFA group than in the NaF group. Lethal effects of HFA are promoted by exposure routes such as inhalation that cause rapid absorption into the body. Even low exposure to HFA can cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis. These complications result in a poor prognosis.

Toxicokinetics and Metabolism Deteriorated by Acute Nephrotoxicity after a Single Intravenous Injection of Hydrofluoric Acid in Rats

“…We also consider that renal tubular injury decreased the urinary excretion of K, and increased NAG/Cr and glucose excretion in the 6.4 and the 9.6 mg/kg groups. Our previous study showed that the serum K level of the 9.6 mg/kg group significantly increased compared with that of the control, and that metabolic acidosis was complicated 3) . Therefore, we consider that renal dysfunction mainly decreased the amount of urinary excretion of HFA from the blood.…”

“…Rats were injected with HFA (3.2, 6.4, or 9.6 mg/kg) or saline. Acute renal dysfunction and electrolyte abnormalities were observed to be significant and dose-dependent 3) . These…”

“…Generally, exposure to highly concentrated HFA results in a high rate of mortality after several hours 1) . Many clinical cases have shown that abnormal levels of serum electrolytes are strongly connected to mortality [2][3][4][5][6] . We previously reported an acute lethal case within 1 h after exposure to HFA solution, even though it was diluted to a concentration below 5%, which is the minimum for industrial use 2) .…”

Time‐dependent Changes of Blood Parameters and Fluoride Kinetics in Rats after Acute Exposure to Subtoxic Hydrofluoric Acid

“…These doses were the minimum and the maximum doses, respectively, in our previous study 9) . All the rats were anesthetized with pentobarbital.…”

“…administration at the maximal dose corresponding to the sublethal dose of HFA (LD 5 ) to model the rapid absorption of HFA into the blood, such as upon acute inhalation exposure. This dose could cause acute renal dysfunction, electrolyte abnormalities and metabolic acidosis after 60 min 9) . However, the early changes associated with harmful effects would rapidly fluctuate owing to the combined effects of dose and time.…”