The very steep dose-effect curves found for the ZnO particles indicate that from a certain concentration, the toxic effect increases very rapidly. For most cell types, the relevant value is in the range of 10-20 µg/ml.
The studies carried out within the project NanoCare on eleven different cell lines of different origins show that these cell lines are differently sensitive to the ZnO particles. Here, too, a relatively high toxicity was found already at low concentrations in some cell lines (LOEL from 5 µg/cm² or approximately 16 µg/ml). For some cells, the threshold values for in vitro apoptosis tests were in the range of 7.5-10 µg/cm^{2 [1]}.
In addition to simple culture systems with only one cell line, also complex so-called co-culture systems were used within NanoCare. Using such systems, the in vivo situation in the body can be displayed better due to simulation of the interaction of the cells. In these systems, ZnO particles were found to cause increased levels of inflammation markers ^[1].
The mechanism responsible for the high toxicity of ZnO particles has not yet been completely clarified. It seems, however, that released zinc ions and reactive oxygen radicals are playing an important role ^[2,3]. Likewise, it is not yet clear whether the observed toxic effect is influenced by the shape and size of the ZnO particles. According to several studies, however, there are no traceable size-dependent effects ^{[3, 4, 5, 6]}.

Coating with gold or aluminum was found to strongly reduce the toxicity of the ZnO nanoparticles ^[7,8,9]. It was postulated, therefore, that the cellular effects are rather caused by electronic properties or solubility than by the size of particles.
ZnO nanoparticles are of interest to medical applications due to the possibility of changing their toxicity through selective modifications ^[10]. Since ZnO nanoparticles seem to be very toxic to cancer cells, (that is, also to many cell lines used in cell culture systems) but not to normal cells ^[11,12], they are investigated, in addition, for their potential cancer fighting capability and their ability to serve as drug-administrating vehicles.

Literature

1. NanoCare 2009, Final Scientific Report, ISBN 978-3-89746-108-6, pdf zum Download (19 MB)
   
2. Xia et al (2008) ACS Nano. 2008 Oct 28;2(10):2121-34
   
3. Song et al (2010) Toxicol Lett. 2010 Dec 15;199(3):389-97
   
4. Lin et al (2009) Journal of Nanoparticle Research Volume 11, Number 1, 25-39
   
5. Deng et al (2009) Nanotechnology. 2009 Mar 18;20(11):115101
   
6. Yuan et al (2009) Colloids Surf B Biointerfaces. 2010 Mar 1;76(1):145-50
   
7. Xu et al (2010) Biomaterials. 2010 Nov;31(31):8022-31
   
8. George et al (2009) ACS Nano. 2010 Jan 26;4(1):15-29
   
9. Yin et al (2010) Langmuir. 2010 Oct 5;26(19):15399-408
   
10. Rasmussen et al (2010) Expert Opin Drug Deliv. 2010 Sep;7(9):1063-77
    
11. Hanley et al (2008) Nanotechnology 19 295103
    
12. Wang et al (2009) J Mater Sci Mater Med. 2009 Jan;20(1):11-22 111

Administration of fine or nanoscale ZnO particles into the lungs of mice or rats was found to cause severe but temporary pneumonia ^[1,2]. Quite interestingly, both the intensity and course of this reaction were practically identical for fine and nanoscale ZnO.

Literature

1. Sayes et al (2008) Toxicological Sciences Volume97, Issue1 Pp. 163-180
   
2. Wahrheit et al (2010) Environ Sci Technol. 2009 Oct 15;43(20):7939-45

It is a fact, however, that inhalation of ZnO fumes during welding may cause metal fume fever ^[1,2]. Bearing the symptoms of influenza, this disease gets better after a few days but may impede lung function if exposure is continued. For all that, it is much more probable that, being used as physical UV filters in suncreams and in cosmetics, the ZnO nanoparticles are taken up via the skin.

Literature

1. Brown et al (1988) British Journal of Radiology (1988) 61, 327-329
   
2. Kuschner et al (1995) J Investig Med. 1995 Aug;43(4):371-8

However, the expected ZnO concentrations in the environment were estimated using computer models ^[1,2]. These models come to different conclusions. In one case, due to the use of consumer products with nanoscale ZnO, concentrations of about 76 mg / l in surface water and 3194 mg / kg in soils were predicted ^[1]. Thus, the expected ZnO levels compared with those of other nanomaterials are very high ^[1,2]. In another computer-model, significantly lower values were calculated. In relation to known toxic concentrations for aquatic organisms, these values result a risk quotient of ~10. This is an indication that a risk posed by nanoscale ZnO for the environment can not be excluded; however, these high concentrations with an environmental risk are only reached in wastewater (e.g. wastewater treatment plants). The dilution in surface waters results in a risk factor of less than 1, i.e. no risk is expected anymore ^[3].

Literature:

1. Tiede K. et al., 2009, Journal of Chromatography A, 1216, 503-509.
   
2. Boxall A.B.A. et al., 2008, Report to DEFRA.
   
3. Gottschalk F. et al., 2009, Environ Sci Technol, 43, 9216-9222.