title: Biodistribution and toxicity of radio-labeled few layer graphene in mice after intratracheal instillation.
abstract: BACKGROUND
  The potential human health risks from graphene inhalation exposure have attracted substantial scientific interest as a result of the numerous exciting potential commercial applications of graphene. However, the long-term distribution of graphene in organisms after inhalation is unknown, largely as a result of challenges associated with accurate graphene quantification.
  
  
  METHODS
  Carbon-14 labeled FLG was used to quantify the in vivo distribution of FLG in mice after oral gavage or intratracheal instillation for up to 3 or 28 days after exposure, respectively.
  
  
  RESULTS
  Intratracheally instilled FLG was mainly retained in the lung with 47% remaining after 4 weeks. Exposure to non-labeled FLG resulted in dose-dependent acute lung injury and pulmonary edema, but these effects were alleviated with time despite the continued presence of FLG in the lungs. One percent and 0.18% of the intratracheally instilled FLG was present in the liver and spleen, respectively, after 14 days by passing through the air-blood barrier, a finding supported by the results of oral gavage experiments which did not show detectable absorption through the gastrointestinal tract. In addition, 46.2% of the intratracheally instilled FLG was excreted through the feces 28 d after exposure.
  
  
  CONCLUSIONS
  Quantitative measurements revealed the elimination mechanism for FLG and its biodistribution for two exposure pathways. Graphene persistence in the lung only caused transient pulmonary effects. The in vivo distribution, elimination, and toxicity results provided here measured using a robust quantitative method support the human health risk assessment of graphene.
authors: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210093, P. R. China. lmao@nju.edu.cn.
authors: Liang
authors: L
authors: Mao
authors: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210093, P. R. China. humaojie1234@126.com.
authors: Maojie
authors: M
authors: Hu
authors: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210093, P. R. China. bcpan@nju.edu.cn.
authors: Bingcai
authors: B
authors: Pan
authors: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210093, P. R. China. ycxie_nju@163.com.
authors: Yongchao
authors: Y
authors: Xie
authors: Material Measurement Laboratory, Biosystems and Biomaterials Division, National Institute of Standards and Technology, 100 Bureau Drive, Stop 8311, Gaithersburg, MD, 20899-0001, USA. elijah.petersen@nist.gov.
authors: Elijah J
authors: EJ
authors: Petersen
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D000091344:Filaggrin Proteins; D006108:Graphite / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D066237:Intestinal Elimination; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D006108:Graphite