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

Kim YR, Park JI, Lee EJ, Park SH, Seong NW, Kim JH, Kim GY, Meang EH, Hong JS, Kim SH, Koh SB, Kim MS, Kim CS, Kim SK, Son SW, Seo YR, Kang BH, Han BS, An SS, Yun HI, Kim MK - Int J Nanomedicine (2014)

Bottom Line: 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.Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions.We speculate that this inflammatory damage might result from continuous irritation caused by both test articles.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea.

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 (ZnO(AE100[-])) or positively (ZnO(AE100[+])) 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. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.

No MeSH data available.


Related in: MedlinePlus

Histopathological changes in the pancreas after treatment with (A and B) ZnOAE100(−) and (C and D) ZnOAE100(+) at a dose of 500 mg/kg for 90 days. The pancreas sections were stained with hematoxylin and eosin. (A and C) Control for acinar cell. (B and D) 500 mg/kg treatment groups.aNotes:aArrows in (B and D) represent acinar cell apoptosis in the pancreas.Abbreviations: A, chronic inflammation; DH, ductular hyperplasia; IL, interstitial lymphoid cell infiltration; NA, normal acinar cell; P, prominent acinar cell; ZnO, zinc oxide; ZnOAE100(−), 100 nm negatively charged ZnO; ZnOAE100(+), 100 nm positively charged ZnO.
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f5-ijn-9-109: Histopathological changes in the pancreas after treatment with (A and B) ZnOAE100(−) and (C and D) ZnOAE100(+) at a dose of 500 mg/kg for 90 days. The pancreas sections were stained with hematoxylin and eosin. (A and C) Control for acinar cell. (B and D) 500 mg/kg treatment groups.aNotes:aArrows in (B and D) represent acinar cell apoptosis in the pancreas.Abbreviations: A, chronic inflammation; DH, ductular hyperplasia; IL, interstitial lymphoid cell infiltration; NA, normal acinar cell; P, prominent acinar cell; ZnO, zinc oxide; ZnOAE100(−), 100 nm negatively charged ZnO; ZnOAE100(+), 100 nm positively charged ZnO.

Mentions: Regardless of the surface charge of ZnO NPs, squamous cell hyperplasia and vacuolation in nonglandular stomach, intracytoplasmic hyaline droplet, submucosal edema and inflammation, eosinophilic chief cell, and mucous cell hyperplasia in glandular stomach were observed in the 500 mg/kg groups of both sexes (Figures 3 and 4). Acinar cell apoptosis and chronic inflammation in the pancreas, retinal atrophy in the eye, and suppurative inflammation in the prostate gland were also observed in the 500 mg/kg groups of both sexes (Figures 5–7). As significant lesions in the stomach, pancreas, eye, and prostate gland were observed in the 500 mg/kg groups, these organs were also examined in the 31.25 mg/kg and 125 mg/kg groups. In the stomach, most lesions observed in the 500 mg/kg group were observed in the 31.25 mg/kg and 125 mg/kg groups and they exhibited dose dependency. The suppurative inflammatory lesion in the prostate gland, which was observed in the 500 mg/kg group, was also observed in the 31.25 mg/kg and 125 mg/kg groups. The lesion of retinal atrophy in the eye was observed in only one animal in the male 125 mg/kg group. However, in the pancreas, most lesions observed in the 500 mg/kg group were not observed in the 31.25 mg/kg and 125 mg/kg groups (data not shown).


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

Kim YR, Park JI, Lee EJ, Park SH, Seong NW, Kim JH, Kim GY, Meang EH, Hong JS, Kim SH, Koh SB, Kim MS, Kim CS, Kim SK, Son SW, Seo YR, Kang BH, Han BS, An SS, Yun HI, Kim MK - Int J Nanomedicine (2014)

Histopathological changes in the pancreas after treatment with (A and B) ZnOAE100(−) and (C and D) ZnOAE100(+) at a dose of 500 mg/kg for 90 days. The pancreas sections were stained with hematoxylin and eosin. (A and C) Control for acinar cell. (B and D) 500 mg/kg treatment groups.aNotes:aArrows in (B and D) represent acinar cell apoptosis in the pancreas.Abbreviations: A, chronic inflammation; DH, ductular hyperplasia; IL, interstitial lymphoid cell infiltration; NA, normal acinar cell; P, prominent acinar cell; ZnO, zinc oxide; ZnOAE100(−), 100 nm negatively charged ZnO; ZnOAE100(+), 100 nm positively charged ZnO.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279774&req=5

f5-ijn-9-109: Histopathological changes in the pancreas after treatment with (A and B) ZnOAE100(−) and (C and D) ZnOAE100(+) at a dose of 500 mg/kg for 90 days. The pancreas sections were stained with hematoxylin and eosin. (A and C) Control for acinar cell. (B and D) 500 mg/kg treatment groups.aNotes:aArrows in (B and D) represent acinar cell apoptosis in the pancreas.Abbreviations: A, chronic inflammation; DH, ductular hyperplasia; IL, interstitial lymphoid cell infiltration; NA, normal acinar cell; P, prominent acinar cell; ZnO, zinc oxide; ZnOAE100(−), 100 nm negatively charged ZnO; ZnOAE100(+), 100 nm positively charged ZnO.
Mentions: Regardless of the surface charge of ZnO NPs, squamous cell hyperplasia and vacuolation in nonglandular stomach, intracytoplasmic hyaline droplet, submucosal edema and inflammation, eosinophilic chief cell, and mucous cell hyperplasia in glandular stomach were observed in the 500 mg/kg groups of both sexes (Figures 3 and 4). Acinar cell apoptosis and chronic inflammation in the pancreas, retinal atrophy in the eye, and suppurative inflammation in the prostate gland were also observed in the 500 mg/kg groups of both sexes (Figures 5–7). As significant lesions in the stomach, pancreas, eye, and prostate gland were observed in the 500 mg/kg groups, these organs were also examined in the 31.25 mg/kg and 125 mg/kg groups. In the stomach, most lesions observed in the 500 mg/kg group were observed in the 31.25 mg/kg and 125 mg/kg groups and they exhibited dose dependency. The suppurative inflammatory lesion in the prostate gland, which was observed in the 500 mg/kg group, was also observed in the 31.25 mg/kg and 125 mg/kg groups. The lesion of retinal atrophy in the eye was observed in only one animal in the male 125 mg/kg group. However, in the pancreas, most lesions observed in the 500 mg/kg group were not observed in the 31.25 mg/kg and 125 mg/kg groups (data not shown).

Bottom Line: 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.Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions.We speculate that this inflammatory damage might result from continuous irritation caused by both test articles.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea.

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 (ZnO(AE100[-])) or positively (ZnO(AE100[+])) 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. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg.

No MeSH data available.


Related in: MedlinePlus