Toxicity of methylmercury (MeHg) to wildlife and humans results from its binding to cysteine residues of proteins, forming MeHg-cysteinate (MeHgCys) complexes that hinder biological functions. MeHgCys complexes can be detoxified in vivo, yet how this occurs is unknown. We report that MeHgCys complexes are transformed into selenocysteinate (Hg(Sec)4) complexes in multiple animals from two phyla (a waterbird, freshwater fish, and earthworms) sampled in different geographical areas and contaminated by different Hg sources. In addition, high energy-resolution Xray absorption spectroscopy (HR-XAS) and chromatography-ICP mass spectrometry of the waterbird liver support the binding of Hg(Sec)4 to selenoprotein P and biomineralization of Hg(Sec)4 to chemically inert nanoparticulate mercury selenide (HgSe). The results provide a foundation for understanding mercury detoxification in higher organisms, and suggest that the identified MeHgCys to Hg(Sec)4 demethylation pathway is common in nature.All data supporting the findings of this study are available within the paper and have been deposited in the U.S. Geological Survey repository ScienceBase. 31 The deposit includes all HR-XANES spectra, the Hg L3-edge HR-EXAFS spectrum of the Clark's grebe liver, and the Cartesian coordinates of the Hg(selenoneine)4 complex and the Hg10(SeMe)20 cluster.

Titanium dioxide in nanoparticulate form is used in large scale in a variety of consumer products including sunscreens. There is an increasing need for methodology for the reliable characterisation of the particle size and size dependent elemental composition in these complex matrices. Such measurement capability is essential for underpinning safety assessments, for quality control of existing products and for correlation of nanoparticle characteristics with biological effects observed in toxicity tests. This work describes the first systematic comparison and optimisation of extraction methods for titanium dioxide nanoparticles in sunscreen samples. Sunscreens were selected because of their wide use, high fat content and matrix of high complexity. Defatting of the sample with hexane followed by bath sonication with an aqueous extractant was found to provide stable suspensions of secondary titanium dioxide particles for their size characterisation by flow field flow fractionation on-line with element selective detection by inductively coupled plasma mass spectrometry. Further addition of a small amount of hexane to the aqueous extractant resulted in particle disaggregation and thus allowed for characterisation of the primary particle size. A novel approach based on sample spiking with aluminium-labelled titanium dioxide reference particles of known size was used to study the effect of extraction and separation conditions on particle size distribution in the presence of the real sample matrix. The developed methodology was applied to analysis of commercial sunscreens with various sun protection factors. Titanium extraction efficiency, particle size distribution and titanium dioxide recovery from the FFF channel were determined for each product.

A new selenized yeast reference material (SELM-1) produced by the Institute for National Measurement Standards, National Research Council of Canada (INMS, NRC) certified for total selenium (2,059+/-64 mg kg(-1)), methionine (Met, 5,758+/-277 mg kg(-1)) and selenomethionine (SeMet, 3,431+/-157 mg kg(-1)) content is described. The +/-value represents an expanded uncertainty with a coverage factor of 2. SeMet and Met amount contents were established following a methanesulfonic acid digestion of the yeast using GC-MS and LC-MS quantitation. Isotope dilution (ID) calibration was used for both compounds, using 13C-labelled SeMet and Met. Total Se was determined after complete microwave acid digestion based on ID ICP-MS using a 82Se spike or ICP-OES spectrometry using external calibration. An international intercomparison exercise was piloted by NRC to assess the state-of-the-art of measurement of selenomethione in SELM-1. Determination of total Se and methionine was also attempted. Seven laboratories submitted results (2 National Metrology Institutes (NMIs) and 5 university/government laboratories). For SeMet, ten independent mean values were generated. Various acid digestion and enzymatic procedures followed by LC ICP-MS, LC AFS or GC-MS quantitation were used. Four values were based on species-specific ID calibration, one on non-species-specific ID with the remainder using standard addition (SA) or external calibration (EC). For total selenium, laboratories employed various acid digestion procedures followed by ICP-MS, AFS or GC-MS quantitation. Four laboratories employed ID calibration, the remaining used SA or EC. A total of seven independent results were submitted. Results for methionine were reported by only three laboratories, all of which used various acid digestion protocols combined with determination by GC-MS and LC UV. The majority of participants submitted values within the certified range for SeMet and total Se, whereas the intercomparison was judged unsuccessful for Met because only two external laboratories provided values, both of which were outside the certified range.

This work represents a first systematic approach to the size-based elemental quantification and size estimation of metal(loid) oxide nanoparticles such as silica (SiO2) in a real food matrix using asymmetric flow field-flow fractionation coupled online with inductively coupled plasma mass spectrometry (ICP-MS) and multi-angle light scattering (MALS) and offline with transmission electron microscopy (TEM) with energy-dispersive X-ray analysis (EDAX). Coffee creamer was selected as the model sample since it is known to contain silica as well as metal oxides such as titania at the milligramme per kilogramme levels. Optimisation of sample preparation conditions such as matrix-to-solvent ratio, defatting with organic solvents and sonication time that may affect nanoparticle size and size distribution in suspensions was investigated. Special attention was paid to the selection of conditions that minimise particle transformation during sample preparation and analysis. The coffee creamer matrix components were found to stabilise food grade SiO2 particles in comparison with water suspensions whilst no significant effect of defatting using hexane was found. The use of sample preparation procedures that mimic food cooking in real life was also investigated regarding their effect on particle size and particle size distribution of silica nanoparticles in the investigated food matrix; no significant effect of the water temperature ranging from ambient temperature to 60 °C was observed. Field-flow fractionation coupled to inductively coupled plasma-mass spectrometry (FFF-ICP-MS) analysis of extracts of both unspiked coffee creamer and coffee creamer spiked with food grade silicon dioxide, using different approaches for size estimation, enabled determination of SiO2 size-based speciation. Element-specific detection by ICP-MS and post-FFF calibration with elemental calibration standards was used to determine the elemental composition of size fractions separated online by FFF. Quantitative data on mass balance is provided for the size-based speciation of the investigated inorganic nano-objects in the complex matrix. The combination of FFF with offline fractionation by filtration and with detection by ICP-MS and TEM/EDAX has been proven essential to provide reliable information of nanoparticle size in the complex food matrix.

Although recent reports suggest that selenium can modulate the activity of cytotoxic drugs, the mechanism underlying this activity remains unclear. This has been investigated using a panel of human B-cell lymphoma cell lines. The cytotoxic effects of chemotherapeutic agents (e.g., doxorubicin, etoposide, 4-hydroperoxycyclophosphamide, melphalan, and 1-B-D-arabinofuranosylcytosine) were increased by up to 2.5-fold when combined with minimally toxic concentrations (EC 5-10 ) of the organic selenium compound, methylseleninic acid (MSA). DNA strand breaks were identified using comet assays, but the measured genotoxic activity of the combinations did not explain the observed synergistic effects in cell death. However, minimally toxic (EC 10 ) concentrations of MSA induced a 50% decrease in nuclear factor-KB (NF-KB) activity after an exposure of 5 h, similar to that obtained with the specific NF-KB inhibitor, BAY 11-7082. Combinations of BAY 11-7082 with these cytotoxic drugs also resulted in synergism, suggesting that the chemosensitizing activity of MSA is mediated, at least in part, by its effects on NF-KB. Basal intracellular selenium concentration was higher in a MSA-sensitive cell line. After exposure to MSA, methylselenocysteine and selenomethionine were identified as the main intracellular species generated. Volatile selenium species, trapped using solid-phase microextraction fibers, were identified as dimethylselenide and dimethyldiselenide. These volatile species are thought to be the most biologically active forms of selenium. Taken together, these results show that the NF-KB pathway is one target for MSA underlying the interaction between MSA and chemotherapy. These data encourage the further clinical development of selenium as a potential modulator of cytotoxic drug activity in B-cell lymphomas.