Perfluorododecanoic Acid Induces Cognitive Deficit in Adult Rats

Abstract

The brain level of perfluorododecanoic acid (PFDoA) was compared with those of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) in rats 9 days after a single oral dose (50 mg/kg). The PFDoA level in the brain was 44.0 ± 2.0 µg/g, which was higher than that in the serum (24.4 ± 1.0 µg/ml). In contrast, the concentrations of PFOA and PFDA in the brain were low (<0.8 and 4.7 ± 0.4 µg/g, respectively), and less than one-tenth of those in the serum. Next, to investigate the effects on brain function, the cognitive function alterations of PFOA, PFDA, and PFDoA were estimated by the novel object recognition test 5-6 days after dosing. A significant decrease in the discrimination index was observed in PFDoA-treated rats while no significant alteration was observed in PFDA- and PFOA-treated rats. The effects of PFDoA were further assessed by other behavioral tests. PFDoA-associated alteration was observed in the elevated-plus maze test, but not in the Y-maze test, open-field test, and forced swim test. A decrease in the discrimination index of the novel object recognition test was dependent on the PFDoA dose and the PFDoA concentration in the brain. PFDoA concentration in the brain was 28.6 ± 2.6 µg/g 30 days after dosing, and a decrease in discrimination index was observed. Taken together, these results suggest that PFDoA distributes in the brain easier than PFOA and PFDA and causes cognitive deficit.

Prenatal and childhood perfluoroalkyl substances exposures and children's reading skills at ages 5 and 8 years

“…Recently, an animal experiments showed PFOA treatment did not cause cognitive deficit in adult rats (Kawabata et al 2017), although the habituation defects and behavior problem were induced in adult mice following neonatal PFOA, PFOS or PFHxS administration (Johansson et al 2008; Viberg et al 2013). Similarly, despite the neurotoxic effect of PFASs was demonstrated by the reduced cell viability, and increased reactive stress and cell apoptosis in vitro (Lee et al 2012; Mashayekhi et al 2015; Reistad et al 2013), PFASs were also identified some contradictory effects.…”

Risk to human health related to the presence of perfluoroalkyl substances in food

“…Kawabata et al. () compared the level of PFDoDA with those of PFOA and PFDA in rats 9 days after a single oral dose (50 mg/kg bw). The PFDoDA level in the brain was 44.4 ± 2.0 μg/g, higher than that in the serum (24.4 ± 1.0 μg/mL).…”

Disposition of perfluorododecanoic acid in male rats after oral administration

“…Our previous study showed that PFOA concentrations in plasma, liver, and the brain were 139, 254, and 3.3 nmol/g, respectively, 2 hr after an intravenous administration of PFOA at a dose of 40 μmol/kg (Kudo et al, 2007). Recently, we have reported that cognitive deficits were found in PFDoA-administered rats (Kawabata et al, 2017). Surprisingly, PFDoA was found to accumulate in the brain at a concentration higher than that in serum 9 days after dosing.…”

“…Thus, the hepatotoxic effects of PFDoA seem to be due to the high concentration of this chemical, therefore, estimation of the tissue concentration may be helpful in evaluating the toxicity of PFDoA. In fact, cognitive deficit has been observed with PFDoA, but not PFOA and PFDA, and only PFDoA was accumulated in the brain (Kawabata et al, 2017). In this context, PFDoA may exhibit toxic effects in tissues where PFDoA accumulates, such as adipose tissue.…”

“…However, a toxicokinetic study of PFAAs with carbon chains longer than 10 remains to be conducted. Recently, we demonstrated that PFDoA accumulates in the brain and causes significant cognitive deficits in rats after a single oral dose of PFDoA (Kawabata et al, 2017). This was markedly different from PFCAs with 6-10 carbon atoms, which were sparsely distributed in the brain (Kudo, 2015).…”