Alteration of hepato-lipidomic homeostasis in A/J mice fed an environmentally relevant PFAS mixture.

In the present study, we have investigated liver lipid homeostasis and corresponding changes in transcript and functional product levels in A/J mice exposed to environmental relevant concentration of per- and polyfluoroalkyl substances (PFAS) mixture. Mice were fed environmentally relevant concentrations of a PFAS mixture during a period of 10 weeks. The concentrations of the 8 individual PFAS in the mixture were chosen based on measured concentrations in earthworms at a Norwegian skiing area. Our data show high liver accumulation of ∑PFAS in exposed mice, which paralleled significant elevation in body weight and hepatosomatic index (HSI) of male mice. UPC2 -MS/MS analysis in both positive and negative mode, respectively, indicated significant differences between control and exposure groups in the liver of exposed mice. Principal component analysis (PCA) of the features revealed separation of control and exposure groups in both sexes. From the significantly differential 207 lipids, only 72 were identified and shown to belong to eight different lipid classes. PCA of fatty acids (FAs) profile showed a clear separation between control and PFAS exposure groups in both female and male mice, with differential abundant levels of 5 and 4 hydrolyzed FAs, respectively. Transcript and protein analysis of genes associated with lipid homeostasis (ppar-α and ß, lxr-α and ß, rxr, fasn and srebp) showed that PFAS exposure produced sex- and individual response related alterations. Glutathione reductase (Gr) activity showed exposure-related changes in both female and male mice, compared with controls. Overall, the present study has demonstrated changes in lipid metabolism after PFAS exposure, showing that PFAS accumulation in the liver resulted to hepatotoxic effects, potential interference with membrane lipid profile and homeostasis, and oxidative stress. Given the structural similarity with FAs, interaction between PFAS and nuclear receptors such as PPARs may have severe consequences for general health and physiology in exposed animals and humans.

Effects of an environmentally relevant PFAS mixture on dopamine and steroid hormone levels in exposed mice.

In the present study, we investigated the dopaminergic and steroid hormone systems of A/J mice fed environmentally relevant concentrations of a perfluoroalkyl substance (PFAS) mixture over a period of 10 weeks. The PFAS mixture was chosen based on measured PFAS concentrations in earthworms at a Norwegian skiing area (Trondheim) and consisted of eight different PFAS. Dietary exposure to PFAS led to lower total brain dopamine (DA) concentrations in male mice, as compared to control. On the transcript level, brain tyrosine hydroxylase (th) of PFAS exposed males was reduced, compared to the control group. No significant differences were observed on the transcript levels of enzymes responsible for DA metabolism, namely - monoamine oxidase (maoa and maob) and catechol-O methyltransferase (comt). We detected increased transcript level for DA receptor 2 (dr2) in PFAS exposed females, while expression of DA receptor 1 (dr1), DA transporter (dat) and vesicular monoamine transporter (vmat) were not affected by PFAS exposure. Regarding the steroid hormones, plasma and muscle testosterone (T), 11-ketotestosterone (11-KT) and 17ß-estradiol (E2) levels, as well as transcripts for estrogen receptors (esr1 and esr2), gonadotropin releasing hormone (gnrh) and aromatase (cyp19) were unaltered by the PFAS treatment. These results indicate that exposure to PFAS doses, comparable to previous observation in earthworms at a Norwegian skiing area, may alter the dopaminergic system of mice with overt consequences for health, general physiology, cognitive behavior, reproduction and metabolism.

Alteration of neuro-dopamine and steroid hormone homeostasis in wild Bank voles in relation to tissue concentrations of PFAS at a Nordic skiing area.

Perfluoroalkyl substances (PFAS) are contaminants that are applied in a wide range of consumer products, including ski products. The present study investigated the neuro-dopamine (DA) and cellular steroid hormone homeostasis of wild Bank voles (Myodes glareolus) from a skiing area in Norway (Trondheim), in relation to tissue concentrations of PFAS. We found a positive association between brain DA concentrations and the concentration of several PFAS, while there was a negative association between PFAS and dopamine receptor 1 (dr1) mRNA. The ratio between DA and its metabolites (3,4-dihydroxyphenylacetic acid: DOPAC and homovanillic acid: HVA) showed a negative association between DOPAC/DA and several PFAS, suggesting that PFAS altered the metabolism of DA via monoamine oxidase (Mao). This assumption is supported by an observed negative association between mao mRNA and PFAS. Previous studies have shown that DA homeostasis can indirectly regulate cellular estrogen (E2) and testosterone (T) biosynthesis. We found no association between DA and steroid hormone levels, while there was a negative association between some PFAS and T concentrations, suggesting that PFAS might affect T through other mechanisms. The results from the current study indicate that PFAS may alter neuro-DA and steroid hormone homeostasis in Bank voles, with potential consequences on reproduction and general health.

Levels, Patterns, and Biomagnification Potential of Perfluoroalkyl Substances in a Terrestrial Food Chain in a Nordic Skiing Area.

Perfluoroalkyl substances (PFASs) are used in a wide range of consumer products, including ski products, such as ski waxes. However, there is limited knowledge on the release of PFASs from such products into the environment and the resultant uptake in biota and transport in food webs. We investigated levels, patterns, and biomagnification of PFASs in soil, earthworms (Eisenia fetida), and Bank voles (Myodes glareolus) from a skiing area in Trondheim, Norway. In general, there was higher PFAS levels in the skiing area compared to the reference area with no skiing activities. The skiing area was dominated by long-chained perfluorocarboxylic acids (PFCAs, ≥70%), while the reference area was dominated by short-chained PFCAs (>60%). The soil PFAS pattern in the skiing area was comparable to analyzed ski waxes, indicating that ski products are important sources of PFASs in the skiing area. A biomagnification factor (BMF) > 1 was detected for Bank volewhole/earthwormwhole for perfluorooctansulfonate in the skiing area. All other PFASs showed a BMF < 1. However, it should be noted that these organisms represent the base of the terrestrial food web, and PFASs originating from ski wax may result to higher exposure in organisms at the top of the food chain.

Decreased plasma levels of perfluoroalkylated substances one year after bariatric surgery.

Per- and polyfluoroalkylated substances (PFASs) are classified as persistent organic pollutants (POPs), and known to be protein bound. The aim of the present study was to determine the levels of 17 different PFASs before and one year after bariatric surgery, and to assess whether weight loss and changed serum protein concentrations could be influencing factors. Plasma samples from 63 patients were analyzed for nine perfluoroalkyl carboxylic acids (PFCAs), three perfluoroalkane sulfonic acids (PFSAs), and five perfluoroalkyl sulfonamide based substances (PASF) before and after surgery. Protein determination was performed in the corresponding serum samples. Mean weight loss one year after surgery was 32.1 kg. The plasma levels of all PFASs decreased with 4-34% compared to preoperative values, and included perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and perfluorobutane sulfonate (PFBS), which have been identified with increasing levels in the general population during recent years. Serum protein concentrations also decreased with 7-8%. Although protein levels were positively correlated with PFOA, PFBS, PFHxS and PFOS, regression analysis revealed that neither weight loss nor reductions in concentrations of serum protein could explain the decreased PFAS levels. The type of surgical procedure did not influence the changes of PFAS levels between the two sample points. A reduced food intake and alterations in absorptions of nutrients after bariatric surgery may have influenced the observed decreasing plasma levels of PFASs.

Effects of a complex contaminant mixture on thyroid hormones in breeding hooded seal mothers and their pups.

There is a general lack of information on the possible effects of perfluoroalkyl substances (PFASs) on thyroid hormones (THs) in wildlife species. The effects of PFASs, which are known endocrine disruptors, on the TH homeostasis in hooded seals (Cystophora cristata) have yet to be investigated. Previously, correlations were found between plasma thyroid hormone (TH) concentrations in hooded seals, and organohalogen contaminants (OHCs) and hydroxyl (OH)-metabolites. Because animals are exposed to multiple contaminants simultaneously in nature, the effects of the complex contaminant mixtures that they accumulate should be assessed. Herein, we analyse relationships between plasma concentrations of multiple contaminants including protein-associated PFASs, hydroxylated metabolites of polychlorinated biphenyls (OH-PCBs) and lipid soluble OHCs and plasma concentrations of free and total THs, i.e. triiodothyronine (FT3, TT3) and thyroxine (FT4, TT4) in hooded seal mothers and their pups. The perfluoroalkyl carboxylates (PFCAs) were the most important predictors for FT3 concentrations and TT3:FT3 ratios in the mothers. The FT3 levels decreased with increasing PFCA levels, while the TT3:FT3 ratios increased. In the pups, hexachlorocyclohexanes (HCHs) were the most important predictors for TT3:FT3 ratios, increasing with increasing HCHs levels. Additionally, perfluoroalkyl sulfonates (PFSAs) and PFCAs were important predictors for FT4:FT3 ratios in hooded seal pups, and the ratio increased with increasing concentrations. The study suggests that PFASs contribute to thyroid disruption in hooded seals exposed to complex contaminant mixtures that include chlorinated and fluorinated organic compounds.

Maternal transfer of perfluoroalkyl substances in hooded seals.

The role of milk in the transfer of perfluoroalkyl substances (PFASs) to offspring is not well known in wildlife. Eight PFASs were quantified in plasma and milk in mother-pup pairs of hooded seals (Cystophora cristata) during the nursing period, and the role of milk in the transfer process was analyzed. Hooded seal was chosen because of its short lactation period (3-4 d), during which the pup feeds only on milk. Placental or lactation transfer would thus be the only source of PFAS in the pup. Of the 8 PFASs analyzed (Σ8 PFAS), 7 were found in all samples; therefore, milk is a source to PFASs in pups. Perfluorooctane sulfonate was the dominant PFAS in all samples. Mean Σ8 PFAS concentrations were 6.0 ng/g protein (36 ng/g wet wt) in maternal plasma, 0.77 ng/g protein (3.2 ng/g wet wt) in milk, and 12 ng/g protein (66 ng/g wet wt) in pup plasma. Measured concentrations in plasma were within ranges previously reported from other seal species, below known toxicity thresholds for experimental rodents. Individual PFASs differed in transfer efficiency from mother to pup, depending on carbon chain lengths, with the lowest relative transfer for the intermediate-chained PFASs (C9 -C10 ). The results show maternal transfer of PFASs via both milk and the placenta, of which placental transfer is the dominant pathway. Environ Toxicol Chem 2017;36:763-770. © 2016 SETAC.