title: Effects of dose volume and delivery device on bronchoalveolar lavage parameters of intratracheally administered nano-sized TiO2in rats.
abstract: The intratracheal (IT) test is useful for screening the pulmonary toxicity of inhaled materials, including nanomaterials. However, a standard procedure has not yet been authorized internationally, and the effects of different test parameters are unknown. To determine appropriate experimental conditions for the IT test, we intratracheally administered nano-sized TiO2to male F344 rats at 3.0 mg/kg body weight by using two delivery devices (gavage needle or microaerosolizer) and dose volumes of 0.5-3.0 mL/kg (gavage needle) or 0.5-2.0 mL/kg (microaerosolizer). We evaluated the pulmonary deposition and interlobar distribution of TiO2at both 30 min and 3 days after administration. In addition, the inflammatory components in bronchoalveolar lavage (BAL) fluid were measured 3 days after administration of TiO2. At dose volumes of 0.5-2.0 mL/kg, the BAL values were comparable regardless of the device used. In addition, pulmonary TiO2burden and lobar concentration patterns were equivalent at all combinations of dose volume and delivery device. In conclusion, the acute pulmonary toxicity of nanomaterials can be assessed effectively by using an IT test in which the test agent is provided to rats at a dose volume of 0.5-2.0 mL/kg with either a gavage needle or microaerosolizer.
authors: CERI Hita, Chemicals Evaluation and Research Institute, Japan, 3-822, Ishii-machi, Hita-shi, Oita, 877-0061, Japan. Electronic address: kobayashi-toshio@ceri.jp.
authors: Toshio
authors: T
authors: Kobayashi
authors: CERI Hita, Chemicals Evaluation and Research Institute, Japan, 3-822, Ishii-machi, Hita-shi, Oita, 877-0061, Japan.
authors: Yutaka
authors: Y
authors: Oshima
authors: CERI Hita, Chemicals Evaluation and Research Institute, Japan, 3-822, Ishii-machi, Hita-shi, Oita, 877-0061, Japan.
authors: Yasuhiro
authors: Y
authors: Tsubokura
authors: CERI Kurume, Chemicals Evaluation and Research Institute, Japan, 3-2-7, Miyanojin, Kurume-shi, Fukuoka, 839-0801, Japan.
authors: Naoki
authors: N
authors: Hashizume
authors: CERI Hita, Chemicals Evaluation and Research Institute, Japan, 3-822, Ishii-machi, Hita-shi, Oita, 877-0061, Japan.
authors: Shozo
authors: S
authors: Ajimi
authors: Chemical Biotesting Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25, Kouraku, Bunkyo-ku, Tokyo, 112-0004, Japan.
authors: Takakazu
authors: T
authors: Kayashima
authors: Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25, Kouraku, Bunkyo-ku, Tokyo, 112-0004, Japan.
authors: Makoto
authors: M
authors: Nakai
authors: National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Takeshi
authors: T
authors: Sasaki
authors: National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Kenji
authors: K
authors: Kawaguchi
authors: Chemicals Assessment and Research Center, Chemicals Evaluation and Research Institute, Japan, 1-4-25, Kouraku, Bunkyo-ku, Tokyo, 112-0004, Japan.
authors: Nobuya
authors: N
authors: Imatanaka
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: Delivery device; Dose volume; Intratracheal administration; Nanomaterial; Titanium dioxide