Developmental toxicity of intravenously injected zinc oxide nanoparticles in rats

• Published in: Archives of pharmacal research Vol. 39; no. 12; pp. 1682 - 1692
• Main Authors: Lee, Jinsoo, Yu, Wook-Joon, Song, Jeongah, Sung, Changhyun, Jeong, Eun Ju, Han, Ji-Seok, Kim, Pilje, Jo, Eunhye, Eom, Ikchun, Kim, Hyun-Mi, Kwon, Jung-Taek, Choi, Kyunghee, Choi, Jonghye, Kim, Heyjin, Lee, Handule, Park, Juyoung, Jin, Seon Mi, Park, Kwangsik
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.12.2016; 대한약학회
• Subjects: abnormal development; administered dose; Animals; bioavailability; blood serum; body weight; breathing; corpus luteum; developmental toxicity; exposure pathways; Female; Fetal Development - drug effects; Fetal Development - physiology; fetus; hematopoiesis; histopathology; Injections, Intravenous; intravenous injection; kidneys; liver; Male; Medicine; nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Nanoparticles - toxicity; no observed adverse effect level; oral administration; Pharmacology/Toxicology; Pharmacy; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - pathology; Rats; Rats, Sprague-Dawley; Research Article; resorption; risk management; thrombosis; Tissue Distribution - drug effects; Tissue Distribution - physiology; toxicity testing; zinc oxide; Zinc Oxide - administration & dosage; Zinc Oxide - metabolism; Zinc Oxide - toxicity; 약학; Rat; Developmental toxicity; Intravenous injection; Zinc oxide nanoparticles
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-016-0767-z

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.