title: Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats.
abstract: Recent toxicity studies of zinc oxide nanoparticles by oral administration showed relatively low toxicity, which may be resulted from low bioavailability. So, the intrinsic toxicity of zinc oxide nanoparticles needs to be evaluated in the target organs by intravenous injection for full systemic concentration of the administered dosage. Although the exposure chance of injection route is low compared to oral and/or inhalation route, it is important to see the toxicity with different exposure routes to get better risk management tool. In this study, the effects of zinc oxide nanoparticles on dams and fetuses were investigated in rats after intravenous injection (5, 10, and 20 mg/kg) from gestation day 6 to 20. Two of 20 dams in the 20 mg/kg treatment group died during the treatment period. Hematological examination and serum biochemistry showed dose-dependent toxicity in treated dams. Histopathological analysis of treated dams revealed multifocal mixed cell infiltration and thrombosis in lung, tubular dilation in kidneys, and extramedullary hemopoiesis in liver. Total dead fetuses (post-implantation loss) were increased and the body weight of fetus was decreased in the 20 mg/kg treatment group. Statistical differences in corpora lutea, resorption, placental weight, morphological alterations including external, visceral and skeletal malformations were not observed in treated groups. Based on the data, lowest observed adverse effect level of injection route was suggested to be 5 mg/kg in dams and no observed adverse effect level was suggested to be 10 mg/kg in fetal developmental toxicity.
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Jinsoo
authors: J
authors: Lee
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Wook-Joon
authors: WJ
authors: Yu
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Jeongah
authors: J
authors: Song
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Changhyun
authors: C
authors: Sung
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Eun Ju
authors: EJ
authors: Jeong
authors: Korea Institute of Toxicology, KRICT, Daejeon, 305-343, Korea.
authors: Ji-Seok
authors: JS
authors: Han
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Pilje
authors: P
authors: Kim
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Eunhye
authors: E
authors: Jo
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Ikchun
authors: I
authors: Eom
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Hyun-Mi
authors: HM
authors: Kim
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Jung-Taek
authors: JT
authors: Kwon
authors: National Institute of Health, Incheon, 404-708, Korea.
authors: Kyunghee
authors: K
authors: Choi
authors: College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 136-714, Korea.
authors: Jonghye
authors: J
authors: Choi
authors: College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 136-714, Korea.
authors: Heyjin
authors: H
authors: Kim
authors: College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 136-714, Korea.
authors: Handule
authors: H
authors: Lee
authors: College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 136-714, Korea.
authors: Juyoung
authors: J
authors: Park
authors: College of Medicine, Eulji University, 14 Hangeulbiseok-gil, Nowon-gu, Seoul, 139-711, Korea. sunmijin@medimail.co.kr.|College of Medicine, Eulji University, Daejeon, 301-746, Korea. sunmijin@medimail.co.kr.
authors: Seon Mi
authors: SM
authors: Jin
authors: College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 136-714, Korea. kspark@dongduk.ac.kr.
authors: Kwangsik
authors: K
authors: Park
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D015034:Zinc Oxide / Q000008:administration & dosage* / Q000378:metabolism / Q000633:toxicity*
chemical_list: D015034:Zinc Oxide
keywords: Developmental toxicity; Intravenous injection; Rat; Zinc oxide nanoparticles