title: Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity.
abstract: Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by intratracheal instillation. We reviewed the effectiveness of intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.
authors.affiliation: Department of Occupational Pneumology, Institute of Industrial Ecological Science, 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 Science, 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 Science, 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 Science, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka 807-8555, Japan. fujishima_kei@med.uoeh-u.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Fujishima
authors.affiliation: Department of Respiratory 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: 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
mesh_terms: D058956:Administration, Mucosal; D000818:Animals; D015415:Biomarkers; D006801:Humans; D007322:Instillation, Drug; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D011014:Pneumonia / Q000175:diagnosis / Q000209:etiology*; D020545:Respiratory Mucosa / Q000187:drug effects*; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
chemical_list: D015415:Biomarkers
keywords: harmful effect; inhalation; intratracheal instillation; nanoparticle
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