title: 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.
abstract: Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung lymph nodes. The results of this 28-day graphene inhalation study suggest low toxicity and a NOAEL of no less than 1.88 mg/m(3).
authors.affiliation: a Institute of Nanoproduct Safety Research, Hoseo University , Asan , Korea .
authors.forename: Jin Kwon
authors.initials: JK
authors.lastname: Kim
authors.affiliation: b Occupational Lung Diseases Institute, KCOMWEL , Incheon , Korea .
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Shin
authors.affiliation: b Occupational Lung Diseases Institute, KCOMWEL , Incheon , Korea .
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Lee
authors.affiliation: b Occupational Lung Diseases Institute, KCOMWEL , Incheon , Korea .
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: a Institute of Nanoproduct Safety Research, Hoseo University , Asan , Korea .
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: b Occupational Lung Diseases Institute, KCOMWEL , Incheon , Korea .
authors.forename: Jin Ee
authors.initials: JE
authors.lastname: Baek
authors.affiliation: a Institute of Nanoproduct Safety Research, Hoseo University , Asan , Korea .
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Kim
authors.affiliation: b Occupational Lung Diseases Institute, KCOMWEL , Incheon , Korea .
authors.forename: Boo Wook
authors.initials: BW
authors.lastname: Kim
authors.affiliation: c KCL , Incheon , Korea .
authors.forename: Jin Sik
authors.initials: JS
authors.lastname: Kim
authors.affiliation: d Department of Mechanical Engineering , Hanyang University , Ansan , Korea .
authors.forename: Gun Ho
authors.initials: GH
authors.lastname: Lee
authors.affiliation: d Department of Mechanical Engineering , Hanyang University , Ansan , Korea .
authors.forename: Kangho
authors.initials: K
authors.lastname: Ahn
authors.affiliation: e Toxicology Laboratory, College of Animal Bioscience and Technology, Konkuk University , Seoul , Korea , and.
authors.forename: Sung Gu
authors.initials: SG
authors.lastname: Han
authors.affiliation: f Department of Work Environment , University of Massachusetts , Lowell , MA , USA.
authors.forename: Dhimiter
authors.initials: D
authors.lastname: Bello
authors.affiliation: a Institute of Nanoproduct Safety Research, Hoseo University , Asan , Korea .
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Yu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D006108:Graphite / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D006108:Graphite
keywords: Nano-structured materials; nanotechnology; nanotoxicology; particle toxicology