Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats

Reardon, AJF; Karathra, J; Ribbenstedt, A; Benskin, JP; MacDonald, AM; Kinniburgh, DW; Hamilton, TJ; Fouad, K; Martin, JW
2019 | Chem. Res. Toxicol. | 32 (8) (1656-1669)
adult-blood donors , attention deficit/hyperactivity disorder , developmental exposure , fish consumption , lactational exposure , locomotor-activity , perfluorinated compounds , perfluoroalkyl acids , persistent organic pollutants , polychlorinated biphenyls
Methylmercury (MeHg) and perfluoro-octanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague-Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Newborns were monitored for physical milestones and reflexive developmental responses, and in juveniles the spontaneous activity, anxiety, memory, and cognition were assessed. Targeted metabolomics of 199 analytes was applied to sectioned brain regions of juvenile offspring. Newborns in the High-Mix group had decreased weight gain as well as delayed reflexes and innate behavioral responses compared to controls and individual chemical groups indicating a toxicological interaction on early development. In juveniles, cumulative mixture effects increased in a dose-dependent manner in tests of anxiety-like behavior. However, other developmental test results suggested antagonism, as PFOS-only and MeHg-only juveniles had increased hyperactivity and thigmotaxic behavior, respectively, but fewer effects in Low-Mix and High-Mix groups. Consistent with these behavioral observations, a pattern of antagonism was also observed in neurochemicals measured in rat cortex, as PFOS-only and MeHg-only juveniles had altered concentrations of metabolites (e.g., lipids, amino acids, and biogenic amines), while no changes were evident in the combined exposures. The cortical metabolites altered in PFOS-only and MeHg-only exposed groups are involved in inhibitory and excitatory neurotransmission. These proof-of-principle findings at relatively high doses indicate the potential for toxicological interaction between PFOS and MeHg, with developmental-stage specific effects. Future mixture studies at lower doses are warranted, and prospective human birth cohorts should consider possible confounding effects from PFOS and mercury exposure on neurodevelopment.

Per- and polyfluoroalkyl substances and fluorine mass balance in cosmetic products from the Swedish market: implications for environmental emissions and human exposure

Lara Schultes; Robin Vestergren; Kristina Volkova; Emelie Westberg; Therese Jacobson; Jonathan P. Benskin
2018 | Environ. Sci.-Process Impacts

Determination of polar organic micropollutants in surface and pore water by high-resolution sampling-direct injection-ultra high performance liquid chromatography-tandem mass spectrometry

Malte Posselt; Anna Jaeger; Jonas L Schaper; Michael Radke; Jonathan P. Benskin
2018 | Environ. Sci.-Process Impacts | 20 (1716-1727)

Sulfluramid use in Brazilian agriculture: A source of per- and polyfluoroalkyl substances (PFASs) to the environment

Rodrigo A Nascimento; Deborah BO Nunoo; Ekhine Bizkarguenaga; Lara Schultes; Itsaso Zabaleta; Jonathan P. Benskin; Saulo Spanó; Juliana Leonel
2018 | Environ. Pollut. | In Press

Inter-individual, inter-city, and temporal trends of per- and polyfluoroalkyl substances in human milk from Swedish mothers between 1972 and 2016

Elisabeth Nyberg; Raed Awad; Anders Bignert; Caroline Ek; Gerd Sällsten; Jonathan P. Benskin
2018 | Environ. Sci.: Processes Impacts | In Press

Nontarget Time Trend Screening in Human Blood

2018 | Environ. Sci. Technol. Lett. | In Press

Determination of Chlorinated Paraffins by Bromide-Anion Attachment Atmospheric-Pressure Chemical Ionization Mass Spectrometry

Yuan B, Benskin JP, Chen CL, Bergman Å
2018 | Environ. Sci. Technol. Lett. | In Press

Biodegradation and Uptake of the Pesticide Sulfluramid in a Soil/Carrot Mesocosm

Itsaso Zabaleta; Ekhine Bizkarguenaga; Deborah B. O. Nunoo; Lara Schultes; Juliana Leonel; Ailette Prieto; Olatz Zuloaga; Jonathan P. Benskin
2018 | Environ. Sci. Technol. | 52 (5) (2603-2611)

Short-, medium-and long-chain chlorinated paraffins in wildlife from paddy fields in the Yangtze River Delta

Du X, Yuan B, Zhou Y, Benskin JP, Qiu Y, Yin G, Zhao J
2018 | Environ. Sci. Technol. | In Press

Perfluoroalkyl acid levels in first-time mothers in relation to offspring weight gain and growth

Gyllenhammar I, Diderholm B, Gustafsson J, Berger U, Ridefelt P, Benskin JP, Lignell S, Lampa E, Glynn A.
2018 | Environ Int | 111 (191-199)

Biotransformation of 8:2 polyfluoroalkyl phosphate diester in gilthead bream (Sparus aurata)

Itsaso Zabaleta; Ekhine Bizkarguenaga; Urtzi Izagirre; Noelia Negreira; Adrian Covaci; Jonathan P. Benskin; Ailette Prieto; Olatz Zuloaga;
2017 | Sci. Total Environ.

Polyfluoroalkyl phosphate esters (PAPs) are high production volume surfactants used in the food contact paper and packaging industry. PAPs may transform to persistent perfluoroalkyl carboxylic acids (PFCAs) under biotic conditions, but little is known about their fate and behavior in aquatic organisms. Here we report for the first time on the uptake, tissue distribution, and biotransformation of 8:2 polyfluoroalkyl phosphate diester (8:2 diPAP) in fish. Gilt-head bream (Sparus aurata) were dosed via the diet (8:2 diPAP at 29μg/ g) for 7days, during which time 8:2 diPAP and its transformation products were monitored in plasma, liver, muscle, gills, bile and brain. 8:2 diPAP tended to accumulate in liver, plasma and gills, and to a lesser extent in muscle, bile and brain. Several transformation products (observed previously in other organisms) were also observed in most tissues and biofluids, including both saturated and unsaturated fluorotelomer acids (8:2 FTCA, 8:2 FTUCA, 7:3 FTCA), and perfluorooctanoic acid (PFOA). 8:2 FTCA was the major metabolite in all tissues/biofluids, except for bile, where PFOA occurred at the highest concentrations. Unexpectedly high PFOA levels (up to 3.7ng/g) were also detected in brain. Phase II metabolites, which have been reported in fish following exposure to fluorotelomer alcohols, were not observed in these experiments, probably due to their low abundance. Nevertheless, the detection of PFOA indicates that exposure to PAPs may be an indirect route of exposure to PFCAs in fish.

Per- and polyfluoroalkyl substances (PFASs) in San Francisco Bay wildlife: Temporal trends, exposure pathways, and notable presence of precursor compounds

Sedlak, MD; Benskin, JP; Wong, A; Grace, R; Greig DJ.
2017 | Chemosphere

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