Calcium neutralizes fluoride bioavailability in a lethal model of fluoride poisoning.
OBJECTIVE
Acute systemic fluoride poisoning can result in systemic hypocalcemia, cardiac dysrhythmias, and cardiovascular collapse. Topical and intraarterial therapy with calcium or magnesium salts reduces dermal injury from fluoride burns. The mechanism of these therapies is to bind and inactivate the fluoride ion. The purpose of this study is to evaluate the effect of calcium and magnesium to decrease the bioavailability of fluoride in a lethal model of fluoride poisoning.


METHODS
In preliminary studies, we determined that fluoride 3.6 mM/kg intraperitoneally in the form of sodium fluoride was uniformly and rapidly fatal in a mouse model. Using this fluoride dose, we performed a controlled, randomized, blinded study of low- and high-dose calcium chloride (1.8 and 3.6 mM/kg intraperitoneally, respectively) and magnesium sulfate (3.6 mM/kg intraperitoneally) to decrease the bioavailability of the fluoride ion. After injection with sodium fluoride, animals were immediately treated with injections of sodium chloride (control), calcium chloride (low- or high-dose), or magnesium sulfate. The major outcome was 6-hour survival using a Cox Proportional Hazard model.


RESULTS
All untreated animals died within 60 minutes. Using a Cox Proportional Hazard model, each 1.8 mM/kg dose of calcium chloride administered reduced the risk of death by 33%. Magnesium sulfate treatment was not associated with a hazard reduction.


CONCLUSIONS
Calcium chloride administered simultaneously with sodium fluoride reduces the bioavailability of fluoride poisoning in a mouse model. The equivalent dose of magnesium sulfate does not significantly decrease fluoride bioavailability.
Heard
K
K
Rocky Mountain Poison and Drug Center, Denver, Colorado, USA. Kennon.Heard@UCHSC.edu
Hill
R E
RE
Cairns
C B
CB
Dart
R C
RC
D000818:Animals; D001682:Biological Availability; D002118:Calcium / Q000494:pharmacology*; D005459:Fluorides / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D016019:Survival Analysis
D008274:Magnesium; D005459:Fluorides; D002118:Calcium