Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 4 No. 4 July 20, 2017 p.179-186
Original Article
Disposition of perfluorododecanoic acid in male rats after oral administration
  • Naomi Kudo (Department of Nutritional Toxicology and Applied Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University / naokudo@josai.ac.jp)
Kohei Kawabata 1) , Suzuka Tamaki 1) , Eri Kokubo 1) , Yukari Kobayashi 1) , Tomoya Shinohara 1) , Ayako Sakai 1) 2) , Hiroshi Kawai 1) , Atsushi Mitsumoto 3) , Yoichi Kawashima 1) , Naomi Kudo 1)
1) Department of Nutritional Toxicology and Applied Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Josai University , 2) Present address: Kitasato Academic Research Organization, Kitasato University , 3) Faculty of Pharmaceutical Sciences, Josai International University
Keywords: Perfluorododecanoic acid, Tissue distribution, Biological half-life, PPARα activation
Abstracts

The disposition of perfluorododecanoic acid (PFDoA), a perfluorocarboxylic acid with 12 carbon atoms, was studied in male rats. Rats received an oral administration of PFDoA at a dose of 50 mg/kg. The body weights of PFDoA-treated rats were slightly less than those of vehicle-treated control rats. PFDoA administration resulted in an increase in liver weight; it was highest at 5 days after the treatment and gradually decreased thereafter. Higher liver weight was observed until 70 days after the treatment. Concentrations of PFDoA in plasma and various tissues were estimated up to 70 days after dosing. A large amount of PFDoA was found in the liver. The PFDoA concentration was 263.94 ± 32.94 μg/g in the liver; the value was 7.93 times higher than that of serum 5 days after treatment. The hepatic PFDoA amount was found to be 29.63% of the dose. A certain amount of PFDoA was found in the brain and adipose tissues where perfluorocarboxylic acids with less than 11 carbon atoms were sparsely distributed. The half-life of PFDoA was 55.3, 49.3, 52.4, 57.1, and 49.8 days for serum, liver, kidneys, brain, and adipose tissue, respectively. PFDoA increased hepatic levels of mRNA for Cyp4A10, Acot1, and Acox1, target genes of PPARα, suggesting that PFDoA can activate PPARα, as was observed with other PFCAs. Elevated levels of these 3 genes were observed 70 days after treatment, and the levels were less than those at 7 days. The differences between PFDoA and PFCAs with less than 11 carbon atoms were discussed.