Perfluoroalkyl substances in circum-ArcticRangifer: caribou and reindeer

Livers of caribou and reindeer (Rangifer tarandus) from Canada (n = 146), Greenland (n = 30), Svalbard (n = 7), and Sweden (n = 60) were analyzed for concentrations of eight perfluoroalkyl carboxylic acids and four perfluoroalkane sulfonic acids. In Canadian caribou, PFNA (range < 0.01–7.4 ng/g wet weight, ww) and PFUnDA (<0.01–5.6 ng/g ww) dominated, whereas PFOS predominated in samples from South Greenland, Svalbard, and Sweden, although the highest concentrations were found in caribou from Southwest Greenland (up to 28 ng/g ww). We found the highest median concentrations of all PFAS except PFHxS in Akia-Maniitsoq caribou (Southwest Greenland, PFOS 7.2–19 ng/g ww, median 15 ng/g ww). The highest concentrations of ΣPFAS were also found in Akia-Maniitoq caribou (101 ng/g ww) followed by the nearby Kangerlussuaq caribou (45 ng/g ww), where the largest airport in Greenland is situated, along with a former military base. Decreasing trends in concentrations were seen for PFOS in the one Canadian and three Swedish populations. Furthermore, PFNA, PFDA, PFUnDA, PFDoDA, and PFTrDA showed decreasing trends in Canada’s Porcupine caribou between 2005 and 2016. In Sweden, PFHxS increased in the reindeer from Norrbotten between 2003 and 2011. The reindeer from Västerbotten had higher concentrations of PFNA and lower concentrations of PFHxS in 2010 compared to 2002. Finally, we observed higher concentrations in 2010 compared to 2002 (albeit statistically insignificant) for PFHxS in Jämtland, while PFNA, PFDA, PFUnDA, PFDoDA, and PFTrDA showed no difference at all.

Predicting the Effects of Per- and Polyfluoroalkyl Substance Mixtures on Peroxisome Proliferator-Activated Receptor Alpha Activity in Vitro

Human exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous, with mixtures of PFAS detected in drinking water, food, household dust, and other exposure sources. Animal toxicity studies and human epidemiology indicate that PFAS may act through shared mechanisms including activation of peroxisome proliferator activated receptor α (PPARα). However, the effect of PFAS mixtures on human relevant molecular initiating events remains an important data gap in the PFAS literature. Here, we tested the ability of modeling approaches to predict the effect of diverse PPARα ligands on receptor activity using Cos7 cells transiently transfected with a full length human PPARα (hPPARα) expression construct and a peroxisome proliferator response element-driven luciferase reporter. Cells were treated for 24 hours with two full hPPARα agonists (pemafibrate and GW7647), a full and a partial hPPARα agonist (pemafibrate and mono(2-ethylhexyl) phthalate), or a full hPPARα agonist and a competitive antagonist (pemafibrate and GW6471). Receptor activity was modeled with three additive approaches: effect summation, relative potency factors (RPF), and generalized concentration addition (GCA). While RPF and GCA accurately predicted activity for mixtures of full hPPARα agonists, only GCA predicted activity for full and partial hPPARα agonists and a full agonist and antagonist. We then generated concentration response curves for seven PFAS, which were well-fit with three-parameter Hill functions. The four perfluorinated carboxylic acids (PFCA) tended to act as full hPPARα agonists while the three perfluorinated sulfonic acids (PFSA) tended to act as partial agonists that varied in efficacy between 28-67% of the full agonist, positive control level. GCA and RPF performed equally well at predicting the effects of mixtures with three PFCAs, but only GCA predicted experimental activity with mixtures of PFSAs and a mixture of PFCAs and PFSAs at ratios found in the general population. We conclude that of the three approaches, GCA most accurately models the effect of PFAS mixtures on hPPARα activity in vitro.HighlightsPerfluorinated carboxylic acids are full human PPARα agonistsPerfluorinated sulfonic acids are partial human PPARα agonistsGCA predicts human PPARα activity for mixtures of full and partial agonistsGCA predicts human PPARα activity for mixtures of agonists and competitive antagonistsGCA accurately predicts human PPARα activity in response to PFAS mixtures

Synthesis and Oxidative Transformations of New Chiral Pinane-Type γ-Ketothiols: Stereochemical Features of Reactions

Chiral γ-ketothiols, thioacetates, thiobenzoate, disulfides, sulfones, thiosulfonates, and sulfonic acids were obtained from β-pinene for the first time. New compounds open up prospects for the synthesis of other polyfunctional compounds combining a biologically active pinane fragment with various pharmacophore groups. It was shown that the syntheses of sulfanyl and sulfonyl derivatives based on 2-norpinanone are characterized by high stereoselectivity in comparison with similar reactions of pinocarvone. The conditions for the preparation of diastereomerically pure thioacetyl and thiobenzoyl derivatives based on pinocarvone, as well as for the chemoselective oxidation of γ-ketothiols with chlorine dioxide to the corresponding thiolsulfonates and sulfonic acids, were selected. The effect of the VO(acac)2 catalyst on the increase in the yields of thiosulfonates was shown. A new direction of the transformation of thiosulfonates with the formation of sulfones was revealed. In the case of pinocarvone-based sulfones, the configuration is inversed at the C2 atom. An epimerization scheme is proposed.