title: Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation and Intratracheal Instillation.
abstract: We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m³) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. yasuom@med.uoeh-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. h-izumi@med.uoeh-u.ac.jp.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. y-yoshiura@med.uoeh-u.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshiura
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. t-tomonaga@med.uoeh-u.ac.jp.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomonaga
authors.affiliation: Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. toyabu@med.uoeh-u.ac.jp.
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.affiliation: Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. tmyojo@med.uoeh-u.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.affiliation: Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. kkawai@med.uoeh-u.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. yatera@med.uoeh-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Department of Chemical Engineering, Hiroshima University, Higashi-Hiroshima 739-8528, Japan. smd@hiroshima-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Department of Chemical Engineering, Hiroshima University, Higashi-Hiroshima 739-8528, Japan. mkubo@hiroshima-u.ac.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kubo
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. k-yamamoto@aist.go.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: National Sanatorium Hoshizuka Keiaien, 4204 Hoshizuka-cho, Kanoya, Kagoshima 893-8502, Japan. skita-kufm@umin.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kitajima
authors.affiliation: Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, 6F IFReC Research Building, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan. kuroetu@ifrec.osaka-u.ac.jp.
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. k-kawaguchi@aist.go.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan. takeshi.sasaki@aist.go.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D015034:Zinc Oxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D016207:Cytokines; D015034:Zinc Oxide
keywords: CINC; inhalation; intratracheal instillation; lung; nanoparticle; neutrophil; zinc oxide