Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea  *These authors contributed equally to this work 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 (ZnOAE100[-]) or positively (ZnOAE100[+]) 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. Bo