A comparative toxicological investigation of perfluorocarboxylic acids in rats by fluorine-19 NMR spectroscopy

Male Fischer-344 rats administered a single intraperitoneal dose of perfluoro-n-octanoic acid (PFOA) or perfluoro-n-decanoic acid (PFDA) display a similar "wasting toxicity" characteristic of perfluorocarboxylic acids, with marked differences in temporal expression. Food/water consumption...

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Bibliographic Details
Published in:Chemical research in toxicology 1992-07, Vol.5 (4), p.512-519
Main Authors: Goecke, Carol M, Jarnot, Bruce M, Reo, Nicholas V
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Body Fluids - metabolism
Caprylates - pharmacokinetics
Caprylates - toxicity
Chemical and industrial products toxicology. Toxic occupational diseases
Decanoic Acids - pharmacokinetics
Decanoic Acids - toxicity
Drinking - drug effects
Eating - drug effects
Fluorocarbons - pharmacokinetics
Fluorocarbons - toxicity
Liver - metabolism
Magnetic Resonance Spectroscopy
Male
Medical sciences
Rats
Rats, Inbred F344
Toxicology
Various organic compounds
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Summary:Male Fischer-344 rats administered a single intraperitoneal dose of perfluoro-n-octanoic acid (PFOA) or perfluoro-n-decanoic acid (PFDA) display a similar "wasting toxicity" characteristic of perfluorocarboxylic acids, with marked differences in temporal expression. Food/water consumption and urine output were monitored daily in PFOA-treated, PFDA-treated, and control rats. Fluorine-19 nuclear magnetic resonance (NMR) spectroscopy was used to monitor these fluorocarbons and possible fluoro metabolites in vivo, and to correlate differences in elimination with differences in effective toxicity. The data reveal a prolonged hypophagic response to PFDA and a more acute but transient response associated with PFOA treatment. PFOA causes a greater decline in food consumption than PFDA within the first 24 h postdose. PFOA-treated rats also show a ca. 2.5-fold increase in urine output on day 1, with only a slight increase in water consumption. In contrast to PFDA, PFOA-treated rats recover from hypophagia within 8 days. Fluorine-19 NMR spectra of various bodily fluids and liver in vivo display resonances of the parent PFOA or PFDA compounds and do not reveal any evidence of metabolism. Inorganic fluoride from dietary sources is detected in urine from both exposed and control rats. Differences in the route of excretion of PFOA vs PFDA are apparent from the spectral signal-to-noise ratio. The data suggest that PFOA is more readily excreted in the urine while PFDA is preferentially carried in bile. These apparent differences in elimination may account for their observed differences in effective toxicity. The acute transient toxicity and higher LD50 associated with PFOA may result from its rapid renal clearance.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx00028a009