A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

Hark-Soo Park,1 Sung-Sup Shin,1 Eun Ho Meang,1 Jeong-sup Hong,1 Jong-Il Park,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Young Lee,1 Dong-Hyouk Jang,1 Jong-Yun Lee,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park6 1General Toxicolo...

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Autores principales: Park HS, Shin SS, Meang EH, Hong JS, Park JI, Kim SH, Koh SB, Lee SY, Jang DH, Lee JY, Sun YS, Kang JS, Kim YR, Kim MK, Jeong J, Lee JK, Son WC, Park JH
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2014
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Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/a6b21ec408884e19bfbdf2946410e63b
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spelling oai:doaj.org-article:a6b21ec408884e19bfbdf2946410e63b2021-12-02T03:56:41ZA 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats1178-2013https://doaj.org/article/a6b21ec408884e19bfbdf2946410e63b2014-12-01T00:00:00Zhttp://www.dovepress.com/a-90-day-study-of-subchronic-oral-toxicity-of-20nbspnm-negatively-char-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Hark-Soo Park,1 Sung-Sup Shin,1 Eun Ho Meang,1 Jeong-sup Hong,1 Jong-Il Park,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Young Lee,1 Dong-Hyouk Jang,1 Jong-Yun Lee,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park6 1General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, Korea; 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 4National Institute of Food and Drug Safety Evaluation, Seoul, Korea; 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea Purpose: The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(-)) NPs in Sprague Dawley rats for 90 days.Methods: The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs.Results: No rats died during the test period. However, ZnOSM20(-) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion: A ZnOSM20(-) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. Keywords: negative charge, oral toxicity study, rat, ZnOPark HSShin SSMeang EHHong JSPark JIKim SHKoh SBLee SYJang DHLee JYSun YSKang JSKim YRKim MKJeong JLee JKSon WCPark JHDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Supplement 2, Pp 79-92 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Park HS
Shin SS
Meang EH
Hong JS
Park JI
Kim SH
Koh SB
Lee SY
Jang DH
Lee JY
Sun YS
Kang JS
Kim YR
Kim MK
Jeong J
Lee JK
Son WC
Park JH
A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
description Hark-Soo Park,1 Sung-Sup Shin,1 Eun Ho Meang,1 Jeong-sup Hong,1 Jong-Il Park,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Young Lee,1 Dong-Hyouk Jang,1 Jong-Yun Lee,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park6 1General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, Korea; 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 4National Institute of Food and Drug Safety Evaluation, Seoul, Korea; 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea Purpose: The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(-)) NPs in Sprague Dawley rats for 90 days.Methods: The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs.Results: No rats died during the test period. However, ZnOSM20(-) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion: A ZnOSM20(-) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. Keywords: negative charge, oral toxicity study, rat, ZnO
format article
author Park HS
Shin SS
Meang EH
Hong JS
Park JI
Kim SH
Koh SB
Lee SY
Jang DH
Lee JY
Sun YS
Kang JS
Kim YR
Kim MK
Jeong J
Lee JK
Son WC
Park JH
author_facet Park HS
Shin SS
Meang EH
Hong JS
Park JI
Kim SH
Koh SB
Lee SY
Jang DH
Lee JY
Sun YS
Kang JS
Kim YR
Kim MK
Jeong J
Lee JK
Son WC
Park JH
author_sort Park HS
title A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
title_short A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
title_full A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
title_fullStr A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
title_full_unstemmed A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats
title_sort 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in sprague dawley rats
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/a6b21ec408884e19bfbdf2946410e63b
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