title: Instillation versus inhalation of multiwalled carbon nanotubes: exposure-related health effects, clearance, and the role of particle characteristics.
abstract: Inhaled multiwalled carbon nanotubes (MWCNTs) may cause adverse pulmonary responses due to their nanoscale, fibrous morphology and/or biopersistance. This study tested multiple factors (dose, time, physicochemical characteristics, and administration method) shown to affect MWCNT toxicity with the hypothesis that these factors will influence significantly different responses upon MWCNT exposure. The study is unique in that (1) multiple administration methods were tested using particles from the same stock; (2) bulk MWCNT formulations had few differences (metal content, surface area/functionalization); and (3) MWCNT retention was quantified using a specialized approach for measuring unlabeled MWCNTs in rodent lungs. Male Sprague-Dawley rats were exposed to original (O), purified (P), and carboxylic acid functionalized (F) MWCNTs via intratracheal instillation and inhalation. Blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected at postexposure days 1 and 21 for quantifying biological responses and MWCNTs in lung tissues by programmed thermal analysis. At day 1, MWCNT instillation produced significant BALF neutrophilia and MWCNT-positive macrophages. Instilled O- and P-MWCNTs produced significant inflammation in lung tissues, which resolved by day 21 despite MWCNT retention. MWCNT inhalation produced no BALF neutrophilia and no significant histopathology past day 1. However, on days 1 and 21 postinhalation of nebulized MWCNTs, significantly increased numbers of MWCNT-positive macrophages were observed in BALF. Results suggest (1) MWCNTs produce transient inflammation if any despite persistence in the lungs; (2) instilled O-MWCNTs cause more inflammation than P- or F-MWCNTs; and (3) MWCNT suspension media produce strikingly different effects on physicochemical particle characteristics and pulmonary responses.
authors.affiliation: Center for Health and the Environment, University of California , Davis, California 95616, United States.
authors.forename: Rona M
authors.initials: RM
authors.lastname: Silva
authors.forename: Kyle
authors.initials: K
authors.lastname: Doudrick
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Franzi
authors.forename: Christel
authors.initials: C
authors.lastname: TeeSy
authors.forename: Donald S
authors.initials: DS
authors.lastname: Anderson
authors.forename: Zheqiong
authors.initials: Z
authors.lastname: Wu
authors.forename: Somenath
authors.initials: S
authors.lastname: Mitra
authors.forename: Vincent
authors.initials: V
authors.lastname: Vu
authors.forename: Gavin
authors.initials: G
authors.lastname: Dutrow
authors.forename: James E
authors.initials: JE
authors.lastname: Evans
authors.forename: Paul
authors.initials: P
authors.lastname: Westerhoff
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.forename: Otto G
authors.initials: OG
authors.lastname: Raabe
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002264:Carboxylic Acids / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects; D055598:Chemical Phenomena; D004305:Dose-Response Relationship, Drug; D006262:Health; D007322:Instillation, Drug; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests; D014867:Water / Q000737:chemistry
chemical_list: D002264:Carboxylic Acids; D037742:Nanotubes, Carbon; D014867:Water
keywords: engineered nanomaterial; inflammation; inhalation exposure; multiwalled carbon nanotube (MWCNT); pulmonary toxicity