Disposition of perfluorododecanoic acid in male rats after oral administration

Abstract

-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.

Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring

“…According to the authors of the original studies, the measured serum concentrations could be effectively described by either monophasic or biphasic kinetics. 68 , 73 , 80 , 81 , 101 , 102 These toxicokinetic evaluations were implemented in our analysis (see Supplemental Materials, “Toxicokinetic model parameterization;” Tables S3–S4; Figures S2–S8). Only PFNA was regarded to be better described by monophasic kinetics rather than biphasic kinetics.…”

“…In some cases the k 10 T 1/2 (HFPO-DA), V 1 (PFDoDA), or k 10 T 1/2 and V 1 (PFNA) were not provided, and thus these values were obtained by optimizing the toxicokinetic models to the empirically obtained serum concentrations over time. 73 , 101 , 105 Further details are provided in Supplemental Material, “Toxicokinetic model parameterization.”…”

“…Correct implementation of the compartment models was confirmed by visual inspection of the modeled serum concentration plotted together with the empirically obtained serum concentrations over time, 68 , 73 , 81 , 101 , 102 , 105 and by evaluating the ratio between the modeled and reported area under the curve (AUC), maximum serum concentration ( ), and time at ( ) values.…”

“…The public literature was screened for toxicokinetic data and models for the 16 PFAS included in the toxicity database, using search engine Google Scholar as well as screening the literature cited in several scientific reports and publications. 44 , 45 , 79 For 10 PFAS [PFBA, 68 PFHxA, 81 PFOA, 81 PFNA, 101 PFDA, 81 perfluorododecanoic acid (PFDoDA), 73 PFBS, 102 PFHxS, 102 PFOS, 102 HFPO-DA 80 ], sufficient model parameter values were obtained from single-dose experiments. In most studies, multiple doses and exposure routes were tested.…”