## 1 Introduction  
The use of nanotechnology has been increasing in industry, biomedicine and research during the last years. According to the conventional definition, nanoparticles (NPs) range from 1 nm to 100 nm. However, this definition cannot be exhaustive. Therefore, several particle systems with diameters larger than 100 nm are commonly also defined as NPs [1]. Compared to larger particles of the same composition, these particles exhibit completely altered mechanical, optical, electrical, magnetic and catalytic properties. Moreover, their size has an effect on the bioactivity as well [2]. Many different NPs, e.g., silver, zinc, gold and titanium are freely available for consumers. Especially for industrial applications, zinc oxide (ZnO) NPs are among the most frequently used nanomaterials. Thus, the amount of synthetically produced ZnO-NPs is continuously increasing, since they are applied as catalysts in the chemical branch, and are a standard ingredient in pharmaceutical and cosmetic products. Furthermore, due to its favorable semi-conductor properties, numerous electronic components contain ZnO [3]. Consequently, there is increasing human exposure to ZnO-NPs. Common routes of uptake into the human organism are the digestive tract, the skin and the respiratory tract. The exposure route via inhalation may affect respiratory and alveolar cells by causing toxic, genotoxic or inflammatory effects [4]. In particular, the incorporation of superfine structures by inhalation has adverse local and systemic side effects, such as increased risk of cardiovascular disorders [5]. A major subject of concern about the increasing usage of ZnO-NPs in consumer goods is that safety aspects remain uncertain, since data on genotoxic and cytotoxic properties of ZnO-NPs are limited. There is an imbalance between the particles' dosages for the inductions of genotoxicity and cytotoxicity [6]. Chemically stable NPs do not show significant toxicity. In contrast to that, NPs which can be oxidized, reduced or dissolved are often cytotoxic and genotoxic to cellular organisms [7]. Concerning this topic, we were able to show a correlation between ion levels and genotoxic reactions of ZnO-NPs in vitro [8]. As a fact, the in vitro results concerning genotoxicity and cytotoxicity do not reflect the in vivo situation precisely. Nevertheless, in vitro results of toxic substances may represent trends to potentially harmful events in the in vivo setting. To our opinion, diverse settings for the analysis of nanotoxicity have to be applied and evaluated. The in vitro analysis of cytotoxicity and genotoxicity of NPs is commonly performed under standard cell culture conditions. The media of these systems are routinely supplemented with animal serum like 10% fetal calf serum (FCS). [PERSON] and [PERSON] published a paper in 2013 on the impact of serum on cytotoxicity of ZnO-NPs. They tested several concentrations of FCS-supplemented cell culture medium and found that there was a correlation between cytotoxicity and inflammation endpoints between the groups. They recommended using serum-based medium for the assessment of the cytotoxicity of NP. However, there is a lack of experiments using pure human serum instead of FCS-supplemented cell culture medium [9]. The protein content, which is crucially influencing toxicity of NPs, is different in the in vivo setting. Thus, the question arises of how the results of genotoxicity and cytotoxicity assays would alter if 100% of human plasma was used instead of cell culture medium containing of 10% FCS. Therefore, the current study aimed to investigate differences in cytotoxic and genotoxic effects of ZnO-NPs in primary human cells. Our group favors the use of human mesenchymal stem cells (hMSCs) for nanotoxicological evaluations, since they are a very stable primary cell system with a high regenerative ability after toxic events and the possibility to perform long-term cultivation.