title: Evaluation of the dose metric for acute lung inflammogenicity of fast-dissolving metal oxide nanoparticles.
abstract: Although surface area metric was suggested as an appropriate dose metric for acute lung inflammation of NPs, it might not be effective for fast-dissolving NPs because they lose their reactive surface when dissolved in the phagolysosomes. Herein, we evaluated the dose metric for fast-dissolving NPs using a rat intratracheal instillation model. A panel of fast-dissolving NPs (CoO, CuO and ZnO) and their constituent metal ions (CoCl2, CuCl2and ZnCl2) were compiled and each compound was intratracheally instilled into the lungs of female Wistar rats at the same molar concentrations in the NP doses (40, 100 and 400 μg/rat). The toxicity endpoints including cytological and biochemical data in bronchoalveolar lavage fluid were evaluated at 24 h after instillation. To evaluate the dose metric, each toxicity endpoint was plotted against the instilled dose (mass or surface area) or the equivalent dose (mass or surface area) that was weighted by the ratio of specific dose-generated responses between metal chlorides. Dose-response curves of fast-dissolving NPs about percentage of granulocytes, lactate dehydrogenase levels and total protein levels showed similar pattern but slightly less potential than those of their respective metal chlorides. When each toxicity endpoint was plotted against the equivalent mass dose, three types of NPs showed more overlapping dose-response curves than other dose metrics. In conclusion, this study implies that the equivalent mass dose is an appropriate dose metric for fast-dissolving NPs and the main factor determining the slope of the dose-response curve is the intrinsic toxicity of the their constituent ions.
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Jiyoung
authors: J
authors: Jeong
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Seonghan
authors: S
authors: Lee
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Sung-Hyun
authors: SH
authors: Kim
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Youngju
authors: Y
authors: Han
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Dong-Keon
authors: DK
authors: Lee
authors: b Division of Toxicological Research , National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety , Osong , Republic of Korea.
authors: Jun-Young
authors: JY
authors: Yang
authors: b Division of Toxicological Research , National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety , Osong , Republic of Korea.
authors: Jayoung
authors: J
authors: Jeong
authors: c Division of Biotechnology Research , Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute , Jeonbuk , Republic of Korea , and.
authors: Changhyun
authors: C
authors: Roh
authors: d Department of Biological Engineering , Biohybrid Systems Research Center, Inha University , Incheon , Republic of Korea.
authors: Yun Suk
authors: YS
authors: Huh
authors: a Lab of Toxicology, Department of Medicinal Biotechnology College of Health Sciences, Dong-A University , Busan , Republic of Korea.
authors: Wan-Seob
authors: WS
authors: Cho
mesh_terms: D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007322:Instillation, Drug; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D019216:Metals, Heavy / Q000737:chemistry / Q000633:toxicity*; D010087:Oxides / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D014132:Trachea / Q000187:drug effects
chemical_list: D019216:Metals, Heavy; D010087:Oxides
keywords: Dose-metric; equivalent dose; fast-dissolving nanoparticles; intratracheal instillation; metal oxide