title: In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice.
abstract: Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length, and surface chemistry in Swiss mice. Transmission electron microscopy (TEM), Raman, near-infrared (NIR), and X-ray photoelectron spectroscopies have been used to characterize the tested materials. The dose of SWNT materials used in this study is considerably higher than that proposed for most biomedical applications, but it was deemed necessary to administer such large doses to accurately assess the toxicological impact of the materials. In an acute toxicity test, SWNTs were administered orally at a dose level of 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiberlike structures. When structure lengths exceeded 10 mum, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (<300 nm) well-individualized SWNTs can escape the reticuloendothelial system to be excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual "molecule-like" species.
authors.affiliation: UMR CNRS 8612 et Laboratoire de Bio-statistiques, Faculte de Pharmacie, Universite Paris-Sud 11, 5, Rue J-B Clement Chatenay-Malabry 92296, France.
authors.forename: Jelena
authors.initials: J
authors.lastname: Kolosnjaj-Tabi
authors.forename: Keith B
authors.initials: KB
authors.lastname: Hartman
authors.forename: Sabah
authors.initials: S
authors.lastname: Boudjemaa
authors.forename: Jeyarama S
authors.initials: JS
authors.lastname: Ananta
authors.forename: Georges
authors.initials: G
authors.lastname: Morgant
authors.forename: Henri
authors.initials: H
authors.lastname: Szwarc
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
authors.forename: Fathi
authors.initials: F
authors.lastname: Moussa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048788:Growth and Development / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000633:toxicity*; D013499:Surface Properties; D018675:Toxicity Tests; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: D037742:Nanotubes, Carbon