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 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Goecke
C M
CM
Department of Biochemistry/Kettering Scott Magnetic Resonance Laboratory, Wright State University, Dayton, Ohio 45429.
Jarnot
B M
BM
Reo
N V
NV
D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002210:Caprylates / Q000493:pharmacokinetics* / Q000633:toxicity; D003652:Decanoic Acids / Q000493:pharmacokinetics* / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005466:Fluorocarbons / Q000493:pharmacokinetics* / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002210:Caprylates; D003652:Decanoic Acids; D005466:Fluorocarbons; C036567:perfluorodecanoic acid; C023036:perfluorooctanoic acid