Studies On Toxic Effects Of Nano-zinc Oxide And Titanium Dioxideand Their Mechanisms Of Toxicity

Due to special physical and chemical properties, nano-zinc oxide（ZnO） and titanium dioxide （TiO₂） have widely used in various fields.They inevitably enter the environment in the process of production,transport and use. Nanoparticles are difficult to settlement in the air withthe small size. They can enter the organism through the respiratory tract,causing harm and injury. This study took ZnO and TiO₂nanoparticles asthe research objects. The toxic effects of ZnO and TiO₂nanoparticles onmice were studied through intratracheal injection. Moreover, mechanismsof toxicity of ZnO and TiO₂nanoparticles were investigated with mousemacrophages as the subject. This study can provide the theoretical basisand the data support for the system evaluation of health hazards and thesafe use of ZnO and TiO₂nanoparticles. The main conclusions are asfollows:1. The acute toxicity of different sized ZnO （30nm and100nmrod-like particles） and TiO₂（5nm,25nm anatase and100nm rutile）nanoparticles in mice was studied after intratracheal administration. Theresults showed that the main target organs for ZnO nanoparticles werelung, liver, pancreas, bone and brain. At low dose （0.05g/kg bw）, ZnOnanoparticles had no apparent toxic effects. At high dose （0.5g/kg bw）,all zinc contents of lung, spleen, pancreas, bone and brain increasedsignificantly. The results of biochemical parameters assay andpathological observation showed that ZnO nanoparticles induced lung,liver and pancreas injury, and caused oxidative stress in mice. Compared with100nm ZnO,30nm ZnO nanoparticles led to more serious injury.The main target organs for TiO₂nanoparticles were lung, liver, spleen,kidney and brain. Biochemical parameters assay showed that5nm and25nm anatase induced more serious liver damage an oxidative stress than100nm rutile. Titanium contents in organic tissues demonstrated5nmand25nm anatase particles were more difficult to remove from the bodyof mice, and easily transferred from the lungs to other tissues and organs.25nm anatase particles may be more toxicity than5nm.2. The toxic effects of ZnO nanoparticles on mouse macrophageswere studied. The results showed that:（1） ZnO nanoparticles had similartoxicity in mouse peritoneal maerophage （Ana-1） and mouse alveolarmacrophages （MH-S）. The IC50values of four ZnO particles were40.28,43.94,40.41and30.95μg/ml to Ana-1cells, and were48.53，47.37，45.43and26.74μg/ml to MH-S cells for fine-ZnO,100nm,30nm and10-30nm ZnO particles, respectively. The toxicity of three different sizedrod-like ZnO particles had no size-dependence.10-30nm spherical ZnOparticles were higher toxic than three rod-like ZnO particles, which maybe related to their shape and structure.（2） The toxic effect of ZnOnanoparticles on Ana-1and MH-S cells was a similar rule. The dissolvedzinc ions played the main role in toxic effect of ZnO nanoparticles. Thetoxic effect of dissolved zinc ions existed a threshold. Under theexperimental conditions, the highest content of dissolved zinc ions wasabout10μg/ml, inducing about50%cell death. The differences intoxicity of different ZnO nanoparticles mainly depended on the toxiceffect of nondissolved ZnO nanoparticles.（3） ZnO nanoparticles couldimpair macrophage phagocytosis, damage cell membrane, causeintracellular oxidative stress, destruct mitochondrial function, eventuallylead to apoptosis or necrosis. At lower dose, induction of MT synthesis byZn played a protective role in cellular response to oxidative stress, ZnOnanoparticles mainly induced cell apoptosis.（4） According to theatomic-scale computer simulation and quantum-chemistry calculation ofZnO nanoparicles, we speculated that there was a larger proportion of（ZnO）n=28,34,48,60clusters in10-30nm spherical ZnO particles. A lot ofnonbonding atoms lied in the surfaces of particles. The delocalization of surface electrons was higher and isotropic. Thus, the toxicity of10-30nmspherical ZnO particles was higher. However, the delocalization ofsurface electrons of rod-like ZnO nanoparticles may be lower anddirectional, resulting in the lower cyctoxicity.3. Compared with ZnO nanoparticles, the toxicity of TiO₂nanoparticles in mouse macrophages was very low, especially in MH-Scells with almost non-toxic. The size and crystal of TiO₂nanoparticlesinfluenced their toxic effect.25nm anatase particles induced thestrongest cytotoxicity and oxidative stress, followed by5nm and100nmanatase particles with similar toxicity,100nm rutile particles with thelowest toxic effect. The production of intracellular ROS was an importantfactor leading to cytotoxicity. However, under the experimentalconditions, TiO₂nanoparticles produced intrinsically a small quantity ofROS. Thus, the toxic effect of TiO₂nanoparticles may mainly depend onthe structural characteristics.