title: Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats.
abstract: Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.
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: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, University of Bath, Bath, UK.
authors.forename: Sung Ha
authors.initials: SH
authors.lastname: Park
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Nak-won
authors.initials: NW
authors.lastname: Seong
authors.affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Kim
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: Eun-Ho
authors.initials: EH
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: Min-Seok
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea.
authors.forename: Cheol-Su
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea.
authors.forename: Soo-Ki
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea.
authors.forename: Sang Wook
authors.initials: SW
authors.lastname: Son
authors.affiliation: Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea.
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Seo
authors.affiliation: Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea.
authors.forename: Boo Hyon
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea.
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Han
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejon, Korea.
authors.forename: Seong Soo A
authors.initials: SS
authors.lastname: An
authors.affiliation: College of Veterinary Medicine, Chungnam National University, Daejon, Korea.
authors.forename: Hyo-In
authors.initials: HI
authors.lastname: Yun
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
mesh_terms: D000284:Administration, Oral; D000818:Animals; D005260:Female; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D010179:Pancreas / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects; D014018:Tissue Distribution; D018675:Toxicity Tests; D015034:Zinc Oxide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D015034:Zinc Oxide
keywords: 90-day oral dose toxicity; no observed adverse effect level; surface charge; zinc oxide nanoparticles