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

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.

Review of the effects of manufactured nanoparticles on mammalian target organs

“…Although skin could be damaged by dermal exposure to NPs, the NPs ability to impair internal organs through penetrated NPs from the skin is extremely limited. Ryu et al (2014) observed dose-dependent inflammation of the skin at the application site in rats after exposure to ZnO NPs for 90 days. Nevertheless, no abnormal findings related to the effect of NPs in other internal organs, such as liver, kidneys and intestine were observed (Ryu et al, 2014).…”

Interactions of Zinc Oxide Nanostructures with Mammalian Cells: Cytotoxicity and Photocatalytic Toxicity

“…Hepatorenal toxicity due to high liver and kidney levels of p53, TNF-α and IL-6. Generation of oxidation stress as shown by low GSH but high thiobarbituric acid reactive substance (TBARS) levels [186] [191] Dermal exposure 75, 180 and 360 mg/kg for 28 d ZnO NPs penetrate into the dermis and reduce its collagen content [192] Intraperitoneal injection Single dose of 2500 mg/kg. Monitoring toxic effects after injection for 24, 48 and 72 h Accumulation in liver, spleen, lung, kidney and heart [193] Intraperitoneal injection 1, 10 and 100 mg/kg.…”

“…Ryu et al conducted a repeated dermal exposure of citrate coated ZnO NPs (20 nm; 250, 500 and 1000 mg/kg bw) to Sprague Dawley rats for 90 days. Transient, dose-dependent irritation of the clipped skin at the application sites was observed [ 191 ]. However, no obvious adverse effects of ZnO NPs up to 1000 mg/kg bw applied dermally to the rats.…”

Nanoparticles and nanofibers for topical drug delivery

“…In recent years, nanosized forms of ZnO and TiO 2 have been optimized to be more transparent, less viscous (more spreadable) [109], and easier to blend, while maintaining their potency against UV irradiation [110]. However, their toxicity profiles need to be assessed since smaller sized particles will likely have different chemical, optical, magnetic, and structural properties [111].…”