Acute fluoride toxicity

The influence of acid-base status

Keith E. Reynolds, Gary M. Whitford, David Henry Pashley

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The influence of preexisting acid-base disturbances on acute fluoride toxicity was studied in anesthetized rats. Metabolic acidosis was induced by the administration of NH4Cl and alkalosis by NaHCO3. Fluoride was infused iv until death occurred. One experiment involved intact animals (n = 18); another study used nephrectomized animals (n = 8). The alkalotic animals survived twice as long, tolerated higher fluoride doses (54.7 vs 29.2 mg/kg, intact; 32.5 vs 25.4 mg/kg, nephrectomized), died with higher plasma fluoride concentrations (2.60 vs 1.79 mm, intact; 3.53 vs 1.77 mm, nephrectomized), and generally had higher systemic blood pressures, heart rates, and glomerular filtration rates at any given plasma fluoride concentration. The renal excretion, renal clearance, and fractional renal clearance ( CF GFR) of fluoride were all consistently higher in the alkalotic animals. Tissue-to-plasma fluoride concentration ratios for heart and skeletal muscle were lower in the alkalotic group, which suggested a smaller volume of distribution for fluoride in alkalosis. This was also indicated by consistently higher plasma fluoride concentrations in the alkalotic animals of the study in which all animals were nephrectomized. It is concluded that a preexisting metabolic alkalosis renders the animal less sensitive to the toxic effects of acutely administered fluoride. The mechanism(s) by which alkalosis protects against fluoride toxicity involves an enhanced renal fluoride clearance rate. It may also involve lower intracellular fluoride concentrations at any given extracellular fluoride level.

Original languageEnglish (US)
Pages (from-to)415-427
Number of pages13
JournalToxicology and Applied Pharmacology
Volume45
Issue number2
DOIs
StatePublished - Jan 1 1978

Fingerprint

Fluorides
Toxicity
Acids
Animals
Alkalosis
Plasmas
Kidney
Poisons
Blood pressure
Acidosis
Glomerular Filtration Rate
Muscle
Rats
Myocardium
Skeletal Muscle
Heart Rate
Tissue

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Acute fluoride toxicity : The influence of acid-base status. / Reynolds, Keith E.; Whitford, Gary M.; Pashley, David Henry.

In: Toxicology and Applied Pharmacology, Vol. 45, No. 2, 01.01.1978, p. 415-427.

Research output: Contribution to journalArticle

Reynolds, Keith E. ; Whitford, Gary M. ; Pashley, David Henry. / Acute fluoride toxicity : The influence of acid-base status. In: Toxicology and Applied Pharmacology. 1978 ; Vol. 45, No. 2. pp. 415-427.
@article{edee4ae3c7f346d592dabc3c2ce0866b,
title = "Acute fluoride toxicity: The influence of acid-base status",
abstract = "The influence of preexisting acid-base disturbances on acute fluoride toxicity was studied in anesthetized rats. Metabolic acidosis was induced by the administration of NH4Cl and alkalosis by NaHCO3. Fluoride was infused iv until death occurred. One experiment involved intact animals (n = 18); another study used nephrectomized animals (n = 8). The alkalotic animals survived twice as long, tolerated higher fluoride doses (54.7 vs 29.2 mg/kg, intact; 32.5 vs 25.4 mg/kg, nephrectomized), died with higher plasma fluoride concentrations (2.60 vs 1.79 mm, intact; 3.53 vs 1.77 mm, nephrectomized), and generally had higher systemic blood pressures, heart rates, and glomerular filtration rates at any given plasma fluoride concentration. The renal excretion, renal clearance, and fractional renal clearance ( CF GFR) of fluoride were all consistently higher in the alkalotic animals. Tissue-to-plasma fluoride concentration ratios for heart and skeletal muscle were lower in the alkalotic group, which suggested a smaller volume of distribution for fluoride in alkalosis. This was also indicated by consistently higher plasma fluoride concentrations in the alkalotic animals of the study in which all animals were nephrectomized. It is concluded that a preexisting metabolic alkalosis renders the animal less sensitive to the toxic effects of acutely administered fluoride. The mechanism(s) by which alkalosis protects against fluoride toxicity involves an enhanced renal fluoride clearance rate. It may also involve lower intracellular fluoride concentrations at any given extracellular fluoride level.",
author = "Reynolds, {Keith E.} and Whitford, {Gary M.} and Pashley, {David Henry}",
year = "1978",
month = "1",
day = "1",
doi = "10.1016/0041-008X(78)90105-9",
language = "English (US)",
volume = "45",
pages = "415--427",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Acute fluoride toxicity

T2 - The influence of acid-base status

AU - Reynolds, Keith E.

AU - Whitford, Gary M.

AU - Pashley, David Henry

PY - 1978/1/1

Y1 - 1978/1/1

N2 - The influence of preexisting acid-base disturbances on acute fluoride toxicity was studied in anesthetized rats. Metabolic acidosis was induced by the administration of NH4Cl and alkalosis by NaHCO3. Fluoride was infused iv until death occurred. One experiment involved intact animals (n = 18); another study used nephrectomized animals (n = 8). The alkalotic animals survived twice as long, tolerated higher fluoride doses (54.7 vs 29.2 mg/kg, intact; 32.5 vs 25.4 mg/kg, nephrectomized), died with higher plasma fluoride concentrations (2.60 vs 1.79 mm, intact; 3.53 vs 1.77 mm, nephrectomized), and generally had higher systemic blood pressures, heart rates, and glomerular filtration rates at any given plasma fluoride concentration. The renal excretion, renal clearance, and fractional renal clearance ( CF GFR) of fluoride were all consistently higher in the alkalotic animals. Tissue-to-plasma fluoride concentration ratios for heart and skeletal muscle were lower in the alkalotic group, which suggested a smaller volume of distribution for fluoride in alkalosis. This was also indicated by consistently higher plasma fluoride concentrations in the alkalotic animals of the study in which all animals were nephrectomized. It is concluded that a preexisting metabolic alkalosis renders the animal less sensitive to the toxic effects of acutely administered fluoride. The mechanism(s) by which alkalosis protects against fluoride toxicity involves an enhanced renal fluoride clearance rate. It may also involve lower intracellular fluoride concentrations at any given extracellular fluoride level.

AB - The influence of preexisting acid-base disturbances on acute fluoride toxicity was studied in anesthetized rats. Metabolic acidosis was induced by the administration of NH4Cl and alkalosis by NaHCO3. Fluoride was infused iv until death occurred. One experiment involved intact animals (n = 18); another study used nephrectomized animals (n = 8). The alkalotic animals survived twice as long, tolerated higher fluoride doses (54.7 vs 29.2 mg/kg, intact; 32.5 vs 25.4 mg/kg, nephrectomized), died with higher plasma fluoride concentrations (2.60 vs 1.79 mm, intact; 3.53 vs 1.77 mm, nephrectomized), and generally had higher systemic blood pressures, heart rates, and glomerular filtration rates at any given plasma fluoride concentration. The renal excretion, renal clearance, and fractional renal clearance ( CF GFR) of fluoride were all consistently higher in the alkalotic animals. Tissue-to-plasma fluoride concentration ratios for heart and skeletal muscle were lower in the alkalotic group, which suggested a smaller volume of distribution for fluoride in alkalosis. This was also indicated by consistently higher plasma fluoride concentrations in the alkalotic animals of the study in which all animals were nephrectomized. It is concluded that a preexisting metabolic alkalosis renders the animal less sensitive to the toxic effects of acutely administered fluoride. The mechanism(s) by which alkalosis protects against fluoride toxicity involves an enhanced renal fluoride clearance rate. It may also involve lower intracellular fluoride concentrations at any given extracellular fluoride level.

UR - http://www.scopus.com/inward/record.url?scp=0018199699&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018199699&partnerID=8YFLogxK

U2 - 10.1016/0041-008X(78)90105-9

DO - 10.1016/0041-008X(78)90105-9

M3 - Article

VL - 45

SP - 415

EP - 427

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -