title: A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats.
abstract: OBJECTIVE
  The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnO(SM20(+))) nanoparticles in Sprague Dawley rats for 90 days.
  
  
  METHODS
  For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnO(SM20(+)) NPs.
  
  
  RESULTS
  No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group.
  
  
  CONCLUSIONS
  There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach.
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Hark-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Seon-Ju
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Taek-Jin
authors.initials: TJ
authors.lastname: Lee
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Geon-Yong
authors.initials: GY
authors.lastname: Kim
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: EunHo
authors.initials: E
authors.lastname: Meang
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Jeong-Sup
authors.initials: JS
authors.lastname: Hong
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Su-Hyon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Koh
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Seung-Guk
authors.initials: SG
authors.lastname: Hong
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Yle-Shik
authors.initials: YS
authors.lastname: Sun
authors.affiliation: Department of Biomedical Laboratory Science, Namseoul University, Cheonan, Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea.
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea.
authors.forename: Meyoung-Kon
authors.initials: MK
authors.lastname: Kim
authors.affiliation: National Institute of Food and Drug Safety Evaluation, Seoul, Korea.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
authors.affiliation: National Institute of Food and Drug Safety Evaluation, Seoul, Korea.
authors.forename: Jong-Kwon
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Woo-Chan
authors.initials: WC
authors.lastname: Son
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Jae-Hak
authors.initials: JH
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002412:Cations; D004487:Edema; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D010179:Pancreas / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D059550:Toxicity Tests, Subchronic; D015034:Zinc Oxide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D002412:Cations; D015034:Zinc Oxide
keywords: ZnO; no-observed-adverse-effect level; oral-toxicity study; positive charge