Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats

Surekha, P.; Kishore, A. Sairam; Srinivas, A.; Selvam, Govindan Sadasivam; Goparaju, A; Reddy, P. Neelakanta; Murthy, P. Balakrishna

doi:10.3109/15569527.2011.595750

Cited by 51 publications

(40 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 Moreover, application of sunscreen containing realistic doses of 20 nm ZnO NPs to rats for 28 days (five times a week) resulted in collagen loss. 21 This collagen loss was explained by the authors as being caused by skin passage of the ZnO NPs at the site of application due to the rat skin being thin.…”

Section: In Vivo Studies Effects Of Airway Exposure In Experimental Amentioning

confidence: 99%

A review of mammalian toxicity of ZnO nanoparticles

Vandebriel¹,

Jong²

2012

NSA

442

247

View full text Add to dashboard Cite

This review summarizes the literature on mammalian toxicity of ZnO nanoparticles (NPs) published between 2009 and 2011. The toxic effects of ZnO NPs are due to the compound's solubility. Whether the increased intracellular [Zn 2+ ] is due to the NPs being taken up by cells or to NP dissolution in medium is still unclear. In vivo airway exposure poses an important hazard. Inhalation or instillation of the NPs results in lung inflammation and systemic toxicity. Reactive oxygen species (ROS) generation likely plays an important role in the inflammatory response. The NPs do not, or only to a minimal extent, cross the skin; this also holds for sunburned skin. Intraperitoneal administration induces neurological effects. The NPs show systemic distribution; target organs are liver, spleen, lung, and kidney and, in some cases, the heart. In vitro exposure of BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells results in cytotoxicity, increased oxidative stress, increased intracellular [Ca 2+ ], decreased mitochondrial membrane potential, and interleukin (IL)-8 production. Decreased contractility of airway smooth muscle cells poses an additional hazard. In contrast to the results for BEAS-2B and A549 cells, in RKO colon carcinoma cells ZnO NPs and not Zn 2+ induce cytotoxicity and mitochondrial dysfunction. Short-term exposure of skin cells results in apoptosis but not in an inflammatory response, while long-term exposure leads to increased ROS generation, decreased mitochondrial activity, and formation of tubular intercellular structures. Macrophages, monocytes, and dendritic cells are affected; exposure results in cytotoxicity, oxidative stress, intracellular Ca 2+ flux, decreased mitochondrial membrane potential, and production of IL-1β and chemokine CXCL9. The NPs are phagocytosed by macrophages and dissolved in lysosomes. In vitro the Comet assay and the cytokinesis-blocked micronucleus assay show genotoxicity, whereas the Ames test does not. This is, however, not confirmed by in vivo genotoxicity assays. Protein binding results in increased stability.

show abstract

Section: In Vivo Studies Effects Of Airway Exposure In Experimental Amentioning

confidence: 99%

A review of mammalian toxicity of ZnO nanoparticles

Vandebriel¹,

Jong²

2012

NSA

442

247

View full text Add to dashboard Cite

show abstract

“…The majority of in vivo toxicity studies on ZnO nanoparticles have investigated acute toxicity and subacute toxicity after a single or repeated dosing, respectively, via inhalation, ingestion, injection, or dermal penetration. [5][6][7][8][9][10] However, much work has yet to been done to determine absorption amounts and bioavailability. Pharmacokinetic (PK) studies require a systematic and thorough quantitative analysis of absorption, distribution, metabolism, and excretion in whole animals, and provide measures of kinetic profiles in plasma and all tissues until the agent is completely cleared from the body.…”

Section: Introductionmentioning

confidence: 99%

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

Choi

Choy

2014

IJN

View full text Add to dashboard Cite

Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle–protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.

show abstract

“…11 Repeated application through dermal routes for 28 days decreases the collagen level at the site of application, which may be induced by oxidative stress. 12 These results suggest that nanotoxicity of ZnO NPs may be mediated by induction of oxidative stress similar to their in vitro toxic mechanisms. However, as these observations regarding nanotoxicity from short-term exposure studies are still limited, long-term exposure studies are required to determine the potential chronic toxicity of ZnO NPs.…”

Section: Introductionmentioning

confidence: 75%

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

Kim¹,

Park²,

Lee³

et al. 2014

IJN

View full text Add to dashboard Cite

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.

show abstract

Repeated dose dermal toxicity study of nano zinc oxide with Sprague-Dawley rats

Cited by 51 publications

References 13 publications

A review of mammalian toxicity of ZnO nanoparticles

A review of mammalian toxicity of ZnO nanoparticles

Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction

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

Contact Info

Product

Resources

About