Evaluation of the neurotoxic effects of engineered nanomaterials in C57BL/6J mice in 28-day oral exposure studies.

In recent years, concerns have emerged about the potential neurotoxic effects of engineered nanomaterials (NMs). Titanium dioxide and silver are among the most widely used types of metallic NMs. We have investigated the effects of these NMs on behaviour and neuropathology in male and female C57BL/6J mice following 28-day oral exposure with or without a 14-day post-exposure recovery. The mice were fed ad libitum with food pellets dosed with 10 mg/g TiO2, 2 mg/g polyvinylpyrrolidone-coated Ag or control pellets. Behaviour was evaluated by X-maze, open field, string suspension and rotarod tests. Histological alterations were analysed by immunohistochemistry and brain tissue homogenates were investigated for markers of oxidative stress, inflammation and blood-brain barrier disruption. Effects of the NMs on tyrosine and serine/threonine protein kinase activity in mouse brains were investigated by measuring kinase activity on peptide microarrays. Markers of inflammation, oxidative stress and blood-brain barrier integrity were not significantly affected in the male and female mice following exposure to Ag or TiO2. Both types of NMs also revealed no consistent significant treatment-related effects on anxiety and cognition. However, in the Ag NM exposed mice altered motor performance effects were observed by the rotarod test that differed between sexes. At 1-week post-exposure, a diminished performance in this test was observed exclusively in the female animals. Cortex tissues of female mice also showed a pronounced increase in tyrosine kinase activity following 28 days oral exposure to Ag NM. A subsequent Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) based toxicokinetic study in female mice revealed a rapid and persistent accumulation of Ag in various internal organs including liver, kidney, spleen and the brain up to 4 weeks post-exposure. In conclusion, our study demonstrated that subacute exposure to foodborne TiO2 and Ag NMs does not cause substantial neuropathological changes in mice. However, the toxicokinetic and specific toxicodynamic findings indicate that long-term exposures to Ag NM can cause neurotoxicity, possibly in a sex-dependent manner.

Concentration-Gradient-Method for sulphur and strontium isotope ratio determination by quadrupole-based inductively coupled plasma mass spectrometry in gypsum.

RATIONALE: The concentration-gradient-method (CGM) was previously introduced as a precise and accurate method for isotope ratio determination by quadrupole-based inductively coupled plasma mass spectrometry (ICP-QMS). The investigation of its potential and advantages in the analysis of analytes with a poor signal-noise ratio (S/N) is important to establish routine isotope ratio analysis industrial applications on these widely used instruments. METHODS: The CGM was applied on isotope measurements of Sr near its limit of quantification (LOQ) and of sulphur where there was a massively interfered 32 S isotope signal in gypsum samples of different origin, in order to demonstrate the advantages of the CGM over the commonly used measurement and evaluation approach. The comparison between the CGM and the classical measurement and evaluation approach was performed with high and low concentration Sr standard solutions, to prove the robustness of the isotope ratio determination. RESULTS: In both cases the CGM reached a recovery rate of approximately 103 %, whereas the classical approach became increasingly inaccurate at lower S/N (recovery of 123 %). In the case of sulphur isotope ratio determination only the CGM enabled a differentiation between geogenic and flue gas desulphurisation plant-originated gypsum samples. CONCLUSIONS: The robustness of the CGM approach was illustrated for gypsum samples with trace strontium concentration and its general applicability to the determination of sulphur isotope ratios by means of quadrupole-based ICP-MS was demonstrated using the example of sulphur in gypsum.

Strontium carbonate precipitation as a sample preparation technique for isotope ratio analysis of Sr in mineral water and wine by quadrupole-based inductively coupled plasma mass spectrometry.

RATIONALE: The defined origin of food products is nowadays often seen as a marker of quality. Stontium (Sr) isotope ratio determination can be used to verify the origin of such food products and it has thus become an important technique. Wine samples in particular are often investigated using this technique. Sr isotopic ratio measurements are often disturbed by isobaric Rb interference, making a separation procedure necessary. In this investigation a very simple and effective procedure for the separation of Rb+ and Sr2+ ions for Sr isotope ratio determination in mineral water and wine samples was developed. METHODS: The classical Sr-carbonate precipitation reaction for the separation of Sr2+ ions from highly soluble Rb+ ions was used. For liquid samples, such as mineral water or wine, a prior digestion is not required. This sample preparation procedure was successfully applied for Sr isotope measurements on a widely available quadrupole-based inductively coupled plasma mass spectrometry (ICP-MS) device in combination with the Concentration-Gradient-Method (CGM). RESULTS: The separation achieved Sr/Rb concentration ratios of 50,000 to 150,000 in water and wine samples. The addition of Ca2+ ions to co-precipitate with the traces of Sr improved the Rb separation and the reproducibility of isotope ratio determination to an uncertainty of ±0.4 ‰ (single standard deviation). This sample preparation approach achieved 2 to 6 times better Rb separation than the commonly applied ion-exchange resin materials. CONCLUSIONS: The quality of the separation is only limited by the number of precipitation repetitions. Moreover, the applicability of quadrupole-based ICP-MS for the characterisation of samples with respect to their origin by means of Sr isotope ratio determination was demonstrated.