title: Comparison of dose-response relations between 4-week inhalation and intratracheal instillation of NiO nanoparticles using polimorphonuclear neutrophils in bronchoalveolar lavage fluid as a biomarker of pulmonary inflammation.
abstract: Inhalation studies and intratracheal instillation studies using laboratory animals are commonly conducted for pulmonary toxicity tests of nanomaterials. In our study, male Wister rats were exposed to nickel oxide (NiO) particles including a nano-scale, even for aerosols and suspensions, in a 4-week inhalation and intratracheal instillation. Using polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid as a biomarker of inflammation, we attempted to quantify the relationship between responses to inhalation and intratracheal instillation of the nanoparticles, based on surface area doses. Four kinds of NiO suspension samples with different specific surface areas were singly injected via the tracheas of the rats. The relationship between the instilled doses and PMN production was examined 3 days and 1 month after the instillation. In parallel, 4-week inhalation studies, using two of the suspensions, were conducted for aerosols generated by a pressurized nebulizer. NiO samples induced PMN responses 3 days after instillation according to the surface area doses, but not the mass doses, as has been reported in many studies. When the same NiO samples were tested in a 4-week inhalation and intratracheal instillation, the amount of pulmonary deposition of the sample after the 4-week inhalation, and an intratracheally instilled dose about ten-times higher, induced similar PMN responses 3 days after termination of inhalation and instillation. Using the relationship between these responses to 4-week inhalation and intratracheal instillation, it may be possible to estimate what aerosol concentrations of other nanomaterials might cause the same responses of PMN production as intratracheal instillation tests.
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojo
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Hashiba
authors.forename: Byeong Woo
authors.initials: BW
authors.lastname: Lee
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Motoi
authors.initials: M
authors.lastname: Todoroki
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nishi
authors.forename: Chikara
authors.initials: C
authors.lastname: Kadoya
authors.forename: Akira
authors.initials: A
authors.lastname: Ogami
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Isamu
authors.initials: I
authors.lastname: Tanaka
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.forename: Kunio
authors.initials: K
authors.lastname: Uchida
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Endoh
authors.forename: Junko
authors.initials: J
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D007322:Instillation, Drug; D007958:Leukocyte Count; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects* / Q000648:ultrastructure; D009532:Nickel / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D059551:Toxicity Tests, Subacute; D014132:Trachea / Q000187:drug effects
chemical_list: D009532:Nickel; C028007:nickel monoxide