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Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

Ryu HJ, Seo MY, Jung SK, Maeng EH, Lee SY, Jang DH, Lee TJ, Jo KY, Kim YR, Cho KB, Kim MK, Lee BJ, Son SW - Int J Nanomedicine (2014)

Bottom Line: Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns.Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking.This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Korea University College of Medicine, Seoul.

ABSTRACT
Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.

No MeSH data available.


Related in: MedlinePlus

Histopathologic changes in the skin after treatment with zinc oxide nanoparticles at a dose of 1,000 mg/kg for 90 days. Skin sections were stained with hematoxylin and eosin (100×). (A) Control group and (B) 1,000 mg/kg treatment group.Note: Arrows in (B) represent hyperkeratosis.
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f1-ijn-9-137: Histopathologic changes in the skin after treatment with zinc oxide nanoparticles at a dose of 1,000 mg/kg for 90 days. Skin sections were stained with hematoxylin and eosin (100×). (A) Control group and (B) 1,000 mg/kg treatment group.Note: Arrows in (B) represent hyperkeratosis.

Mentions: The main sign associated with application of ZnO NPs was formation of skin crusts. At first, this appeared in the G5 (1,000 mg/kg) group 2 days after initiation of ZnOSM20(−), and all groups showed crust formation in a dose-dependent manner. Skin crusts also appeared in the vehicle control group, but resolved after 7 days. Skin crusts from male rats in the 1,000 mg/kg group were biopsied, and found to contain areas of hyperkeratosis and papillomatosis when compared with the normal skin of controls (Figure 1). Scar tissue developed at the application site in one female rat in the G5 group. No difference in body weight was observed between the experimental and control groups. Food intake in male rats from the 500 mg/kg and 1,000 mg/kg groups was significantly decreased in comparison with that in the control group at week 2. Food intake was decreased in female rats from the 250 mg/kg group at week 1 and increased in the 1,000 mg/kg group at week 2 in comparison with the control group. During the recovery period, food intake was decreased in male rats in the 1,000 mg/kg group after week 2 of recovery. Male rats in the 1,000 mg/kg group consumed less water than the control group at week 11. In recovery, water consumption increased significantly in female rats from the 1,000 mg/kg group at weeks 1 and 2. All of these changes were considered to be temporary, given that body weight did not change significantly. Further, these changes were not dose-dependent, so were not considered to be toxic effects of ZnO NPs.


Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats.

Ryu HJ, Seo MY, Jung SK, Maeng EH, Lee SY, Jang DH, Lee TJ, Jo KY, Kim YR, Cho KB, Kim MK, Lee BJ, Son SW - Int J Nanomedicine (2014)

Histopathologic changes in the skin after treatment with zinc oxide nanoparticles at a dose of 1,000 mg/kg for 90 days. Skin sections were stained with hematoxylin and eosin (100×). (A) Control group and (B) 1,000 mg/kg treatment group.Note: Arrows in (B) represent hyperkeratosis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279760&req=5

f1-ijn-9-137: Histopathologic changes in the skin after treatment with zinc oxide nanoparticles at a dose of 1,000 mg/kg for 90 days. Skin sections were stained with hematoxylin and eosin (100×). (A) Control group and (B) 1,000 mg/kg treatment group.Note: Arrows in (B) represent hyperkeratosis.
Mentions: The main sign associated with application of ZnO NPs was formation of skin crusts. At first, this appeared in the G5 (1,000 mg/kg) group 2 days after initiation of ZnOSM20(−), and all groups showed crust formation in a dose-dependent manner. Skin crusts also appeared in the vehicle control group, but resolved after 7 days. Skin crusts from male rats in the 1,000 mg/kg group were biopsied, and found to contain areas of hyperkeratosis and papillomatosis when compared with the normal skin of controls (Figure 1). Scar tissue developed at the application site in one female rat in the G5 group. No difference in body weight was observed between the experimental and control groups. Food intake in male rats from the 500 mg/kg and 1,000 mg/kg groups was significantly decreased in comparison with that in the control group at week 2. Food intake was decreased in female rats from the 250 mg/kg group at week 1 and increased in the 1,000 mg/kg group at week 2 in comparison with the control group. During the recovery period, food intake was decreased in male rats in the 1,000 mg/kg group after week 2 of recovery. Male rats in the 1,000 mg/kg group consumed less water than the control group at week 11. In recovery, water consumption increased significantly in female rats from the 1,000 mg/kg group at weeks 1 and 2. All of these changes were considered to be temporary, given that body weight did not change significantly. Further, these changes were not dose-dependent, so were not considered to be toxic effects of ZnO NPs.

Bottom Line: Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns.Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking.This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Korea University College of Medicine, Seoul.

ABSTRACT
Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally.

No MeSH data available.


Related in: MedlinePlus