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Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.

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Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal‐free risk assessment of new chemicals and drugs. Microfluidic cell‐based devices allow high‐throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal‐free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo‐like in vitro cell cultivation. It is equipped with a wafer‐based silicon chip including integrated electrodes and a microcavity. A proof‐of‐concept using different relevant cell models shows its suitability for label‐free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label‐free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole‐body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments.

This work focuses on degradation of α‐tocopherol and formation of α‐tocopherol degradation products in sunflower oil heated at frying temperature. We determined the content and measured the kinetics of α‐tocopherol, α‐tocopheryl quinone, α‐tocopheryl fatty acid formation in heated sunflower oil without aeration (So) and in aerated oil (air flow 20 L/h) (SoAir). During 10 h of So oil heating, the α‐tocopherol was depleted and the content of α‐tocopheryl quinone in So grew from 3 to 84 mg/kg, as did the content of tocopherol free fatty acid esters from the initial 5 to 185 mg/kg. In SoAir oil, the rate constants of formation and decomposition of tocopherol degradation products were determined. Accelerated oxidation in SoAir caused depletion of the degradation products of tocopherol after 2 h of heating. The reason for this was significant oxidation and polymerization of fatty acids in SoAir oil. The unique features of this work are the syntheses and spectral analysis of tocopherol oxidation products and the development of a suitable method for quantitative analysis of α‐tocopheryl fatty acids. For the first time, we confirmed formation and degradation of tocopheryl fatty acids during oil heating at frying temperature. Practical applications: All the results presented here, consisting of organic syntheses, qualitative and quantitative analysis of α‐tocopheryl fatty acids as well as oxidation and degradation products of tocopherols and fatty acids, will aid future research focused on the degradation of tocopherols. So far the content of α‐tocopheryl fatty acids has not been determined by GC‐FID or HPLC‐UV. This is why there has been little interest in α‐tocopheryl fatty acids, although they are formed both in culinary treatment of food and in oil refining. Free fatty acids (FFAs), fatty acids (FAs), oxidation [o], products (i) and products (ii) are unspecified products of α‐tocopheryl FAs and α‐TQ degradation. Degradation products of α‐tocopherol were formed in heated sunflower oil and further heating of oil caused decomposition of α‐tocopherol degradation products.

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Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects.