Biodistribution And Toxicity Of C-14 Labelled Graphene In Mice

Graphene and its derivatives showed vast application prospect due to its exceptional properties.It is no doubt that the possibility of human exposure to graphene and its derivatives will substantially increase with the extended application range and increased production of graphene.At present information about potential biological health risks of graphene is seriously limited.So it is very important to assess potential biological health risks of graphene and its derivatives systematically.In this study,14C radioactive isotopes labeling method was used to label graphene so as to solve the problem of quantify carbon nanomaterials in biological matrices.Then biodistribution pattern and toxicity of graphene were studied after mice were exposed using different exposure route.The main conclusion are as follows:Firstly,graphene would mainly deposit in lung after intratracheal instillation.A part of graphene would be cleared from lung to gastrointestinal tract via mucociliary clearance and macrophages and then be excreted via feces.Graphene detected in liver and spleen indicate that a small part of graphene has passed air-blood barrier and entered into blood circulation.Exposure of graphene to lung via intratracheal instillation would cause acute lung injury,which mainly characterized by inflammatory cell infiltration,cell injury and pulmonary edema.And acute lung injury is dosage-dependent.As time goes,acute pulmonary will be alleviated despite the continued presence of FLG in the lungs.Twenty-eight days later,no obvious changes were observed in pathological sections of mice,which were intratracheally instilled 50 ?g graphene.Secondly,in vivo behavior of graphene after oral gavage was studied.Graphene would not be adsorbed by the digestion system after oral gavage.Almost complete excretion of graphene occurred 3 days after oral feeding.Body weight change,organ coefficient,antioxidant enzyme,markers of DNA damage and lipid peroxidation were measured.But exposure of graphene did not cause significant difference to indices mentioned above even mice were gavaged continuously at a dose of 100 ?g graphene in a period of 28 days.In addition,histological examinations were performed but no significant pathological changes were observed.But in our study,graphene were demonstrated to influence the intestinal microbial community structure of mice.Continuous exposure of graphene via gavage affect the relative abundance of mice intestinal microbial community.Finally,intravenous injection was used as an exposure route to assess potential health risks of graphene in vivo.Biodistribution results revealed that the graphene mainly accumulated in liver and spleen after intravenous injection.What's more,a small part of graphene would retain in lung,intestine and stomach.Graphene that accumulated in liver and spleen was somewhat bio-persistent and difficult to excrete via feces and urine.But graphene do not cause appreciable toxicity at a tested dose of 1 mg/kg bw to the treated mice in a period of 30 days as evidenced by conventional toxic indicators and histological examinations.Only slight increase of 8-OHdG in liver were observed due to exposure of graphene.