# Safe Functional Modified CuO Nanoparticles?
## 2 Safe(r)-By-Design CuO Nanoparticles
### Surface Modification by Coating or Capping
[53] concluded that coated CuO nanoparticles were more toxic in acute tests with _Daplinia magna_ than pristine CuO nanoparticles. [PERSON] et al. [54] found that coatings of CuO nanoparticles with PEG and carboxylate reduced the cytotoxicity in the human cell lines THP-1 and HACAT, and that a methylaminated organic coating increased cytotoxicity. Extrapolation of these tests to human organisms is subject to uncertainty [49; 50; 51]. [PERSON] et al. [55] did show that pristine, methylaminated- and carboxylate-coated CuO nanoparticles strongly exacerbated allergen-induced lung inflammation in mice, but that the exacerbation was much less in the case of PEGylated CuO nanoparticles. [PERSON] et al. [48] studied the effect on mussels (_Mytilus_ spp.) of pristine CuO nanoparticles and CuO nanoparticles coated with the same organic substances as used by [PERSON] et al. [43]. The focus was on gill cells, lysosomes and haemocytes. Genotoxicity affecting DNA in gill cells and haemocytes was found for both pristine and coated CuO nanoparticles. Based on acute toxicity by lysosomes and haemocytes, the hazard potential of PEG-coated CuO nanoparticles was found to be larger than for the pristine CuO nanoparticles. Chronic exposures suggested lower levels of oxidative stress associated with pristine CuO nanoparticles than with CuO nanoparticles that had carboxylate coatings. [PERSON] et al. [42] found that in an acute toxicity test coating or capping with organic substances (citrate, ascorbate, PEI and polyvinylpyrrolidone (PVP)) of CuO nanoparticles increased the negative impact on earthworm coelomocytes compared with pristine CuO nanoparticles. In a safer-by-design study, [PERSON] et al. [44] considered surface-modification of CuO nanoparticles with citrate, ascorbate, PEI and PVP. These modifications were tested in a mesocosm with six soil invertebrate species (consumers) during relatively long periods, up to 84 days [44]. In this test, overall hazard was reported to be reduced by PEI, but actually increased by citrate and ascorbate modifications, whereas PVP had hardly any effect. Responses differed between species, suggesting species-specific response mechanisms. [PERSON] et al. [44] stressed the importance of long-term testing to assess nanoparticle hazard and stated that multispecies testing increases the relevance to ecological hazard. Multigenerational tests would seem preferable because, as pointed out by [PERSON] et al. [56] \begin{table}
\begin{tabular}{c c c} \hline \hline \multirow{2}{*}{**Study**} & \multirow{2}{*}{**Object of Test**} &
\begin{tabular}{c} **Hazard of PEGylated CuO Nanoparticles** \\ **Compared with the Hazard of Pristine** \\ **Nanoparticles** \\ \end{tabular} \\ \hline [PERSON] et al. [43] & Earthworms & Reduced \\ \hline [PERSON] et al. [48] & Haemocytes and lysosomes of mussels & Increased \\ \hline [PERSON] et al. [53] & Daphnia magna & Increased \\ \hline [PERSON] et al. [54] & THP-1 and HACA human cell lines & Reduced \\ \hline [PERSON] et al. [55] & Lungs of mice & Reduced \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Hazard of PEGylated CuO nanoparticles compared with pristine CuO nanoparticles. and [PERSON] et al. [57], there is evidence for transgenerational epigenetic effects. Extrapolation of these findings to other organisms that may be exposed to surface-modified CuO nanoparticles in a variety of environments is beset by uncertainties [50; 52; 58]. In proving that CuO nanoparticles with coatings or cappings are safe or safer, the robustness of coatings or cappings under conditions encountered in their use stage and beyond should be considered [50]. None of the studies discussed here addressed the robustness of coatings or cappings. In summary: In the studies discussed here, the negative impacts of CuO nanoparticles can be decreased, increased and remain unaffected by coating or capping with organic substances.