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

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 - Int J Nanomedicine (2014)

Bottom Line: The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects.Furthermore, the NPs were associated with a number of undesirable systemic actions.Thus, their use in humans must be approached with caution.

View Article: PubMed Central - PubMed

Affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.

ABSTRACT

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 (ZnO(SM20(-))) 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, ZnO(SM20(-)) 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 ZnO(SM20(-)) 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.

No MeSH data available.


Related in: MedlinePlus

Histopathological findings of the glandular stomach. (A) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal submucosa (NS) in the H&E-stained glandular stomach. (B) Submucosal inflammatory cell infiltration in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the submucosal inflammatory cell infiltration (SI) in the H&E-stained glandular stomach. (C) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal parietal cell distribution (arrows) in the Alcian blue-stained glandular stomach. (D) Proliferative changes in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the mucous cell hyperplasia (arrows) in the Alcian blue-stained glandular stomach.Note: Scale bars, 100 μm.Abbreviations: H&E, hematoxylin and eosin; SD, Sprague Dawley; ZnOSM20(−) NPs, 20 nm, negatively charged ZnO nanoparticles.
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f4-ijn-9-079: Histopathological findings of the glandular stomach. (A) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal submucosa (NS) in the H&E-stained glandular stomach. (B) Submucosal inflammatory cell infiltration in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the submucosal inflammatory cell infiltration (SI) in the H&E-stained glandular stomach. (C) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal parietal cell distribution (arrows) in the Alcian blue-stained glandular stomach. (D) Proliferative changes in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the mucous cell hyperplasia (arrows) in the Alcian blue-stained glandular stomach.Note: Scale bars, 100 μm.Abbreviations: H&E, hematoxylin and eosin; SD, Sprague Dawley; ZnOSM20(−) NPs, 20 nm, negatively charged ZnO nanoparticles.

Mentions: Most of the organs appeared normal in the experimental groups. However, acinar cell apoptosis, ductular hyperplasia, periductular lymphoid cell infiltration, and regenerative acinar cells were all observed in the pancreas of the male and female 500 mg/kg groups, and minimal-to-severe grade retinal atrophy was observed in the male 250 and 500 mg/kg groups and the female 500 mg/kg group (illustrated for a male rat in the 500 mg/kg group in Figure 2). In all treatment groups, various kinds of gastric lesions in varying grades were observed. Therefore, we examined these lesions in more detail by dividing the stomach into three parts: the forestomach, the limiting ridge, and the glandular stomach (Figures 3 and 4).


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

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 - Int J Nanomedicine (2014)

Histopathological findings of the glandular stomach. (A) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal submucosa (NS) in the H&E-stained glandular stomach. (B) Submucosal inflammatory cell infiltration in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the submucosal inflammatory cell infiltration (SI) in the H&E-stained glandular stomach. (C) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal parietal cell distribution (arrows) in the Alcian blue-stained glandular stomach. (D) Proliferative changes in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the mucous cell hyperplasia (arrows) in the Alcian blue-stained glandular stomach.Note: Scale bars, 100 μm.Abbreviations: H&E, hematoxylin and eosin; SD, Sprague Dawley; ZnOSM20(−) NPs, 20 nm, negatively charged ZnO nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279770&req=5

f4-ijn-9-079: Histopathological findings of the glandular stomach. (A) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal submucosa (NS) in the H&E-stained glandular stomach. (B) Submucosal inflammatory cell infiltration in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the submucosal inflammatory cell infiltration (SI) in the H&E-stained glandular stomach. (C) Normal glandular stomach of a male SD rat administered 0 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the normal parietal cell distribution (arrows) in the Alcian blue-stained glandular stomach. (D) Proliferative changes in the glandular stomach of a male SD rat administered 500 mg/kg ZnOSM20(−) NPs by gavage for 90 days. Note the mucous cell hyperplasia (arrows) in the Alcian blue-stained glandular stomach.Note: Scale bars, 100 μm.Abbreviations: H&E, hematoxylin and eosin; SD, Sprague Dawley; ZnOSM20(−) NPs, 20 nm, negatively charged ZnO nanoparticles.
Mentions: Most of the organs appeared normal in the experimental groups. However, acinar cell apoptosis, ductular hyperplasia, periductular lymphoid cell infiltration, and regenerative acinar cells were all observed in the pancreas of the male and female 500 mg/kg groups, and minimal-to-severe grade retinal atrophy was observed in the male 250 and 500 mg/kg groups and the female 500 mg/kg group (illustrated for a male rat in the 500 mg/kg group in Figure 2). In all treatment groups, various kinds of gastric lesions in varying grades were observed. Therefore, we examined these lesions in more detail by dividing the stomach into three parts: the forestomach, the limiting ridge, and the glandular stomach (Figures 3 and 4).

Bottom Line: The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects.Furthermore, the NPs were associated with a number of undesirable systemic actions.Thus, their use in humans must be approached with caution.

View Article: PubMed Central - PubMed

Affiliation: General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea.

ABSTRACT

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 (ZnO(SM20(-))) 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, ZnO(SM20(-)) 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 ZnO(SM20(-)) 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.

No MeSH data available.


Related in: MedlinePlus