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Zinc Oxide
Nanotechnology, Cosmetics and the Skin: Is There a Health Risk?
Nohynek GJ, Dufour EK, Roberts MS
Skin Pharmacol Physiol 2008;21:136-149
Cosmetic formulations may contain nano-emulsions and microscopic vesicles consisting of traditional cosmetic materials, although it is uncertain whether they should be qualified as actual nanomaterials. Vesicle materials do not penetrate into living human skin. Vesicle formulations may enhance or reduce skin absorption of ingredients, albeit at a limited scale. Sunscreens contain TiO2 or ZnO nanoparticles (NP), which are efficient UV filters. A number of studies suggest that insoluble NP do not penetrate into or through human skin. The results of in vivo toxicity tests showed that TiO2 and ZnO NP are non-toxic. In vitro and in vivo cytotoxicity, genotoxicity, photogenotoxicity, acute toxicity, sensitisation and ecotoxicology studies on TiO2 NP found no difference in the safety profile of micro- or nano-sized materials, all of which were non-toxic. Although some in vitro investigations on TiO2 particles reported cell uptake, oxidative cell damage or genotoxicity, these results may be secondary to phagocytosis of cells exposed to excessive particle concentrations. Studies on wear debris nano- and microparticles support the traditional view that toxicity of small particles is related to their chemistry, rather than their particle size. There is little evidence supporting a general rule that adverse effects of particles on the skin or other tissues increase with smaller particle size, or produce novel toxicities relative to those of larger particles. Overall, the current evidence suggests that nano-sized cosmetic or sunscreen ingredients pose no potential risk to human health, whereas their use in sunscreens has large benefits, such as the protection of human skin against skin cancer.
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Int J Dermatol. 2002 Sep;41(9):606-11.
Evidence supporting zinc as an important antioxidant for skin.
Rostan EF, DeBuys HV, Madey DL, Pinnell SR.
Duke University, Durham, NC 27710, USA.
Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zinc's antioxidant role in protecting against free radical-induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health. Abundant evidence demonstrates the antioxidant role of zinc. Topical zinc, in the form of divalent zinc ions, has been reported to provide antioxidant photoprotection for skin. Two antioxidant mechanisms have been proposed for zinc: zinc ions may replace redox active molecules, such as iron and copper, at critical sites in cell membranes and proteins; alternatively, zinc ions may induce the synthesis of metallothionein, sulfhydryl-rich proteins that protect against free radicals. No matter how they work, topical zinc ions may provide an important and helpful antioxidant defense for skin.
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Skin Pharmacol Physiol 2007; 20:148-154
Human Skin Penetration of Sunscreen Nanoparticles: In-vitro Assessment of a Novel Micronized Zinc Oxide Formulation
Sheree E. Cross, Brian Innes, Michael S. Roberts, Takuya Tsuzuki, Terry A. Robertson, Paul McCormick
The extent to which topically applied solid nanoparticles can penetrate the stratum corneum and access the underlying viable epidermis and the rest of the body is a great potential safety concern. Therefore, human epidermal penetration of a novel, transparent, nanoparticulate zinc oxide sunscreen formulation was determined using Franz-type diffusion cells, 24-hour exposure and an electron microscopy to verify the location of nanoparticles in exposed membranes. Less than 0.03% of the applied zinc content penetrated the epidermis (not significantly more than the zinc detected in receptor phase following application of a placebo formulation). No particles could be detected in the lower stratum corneum or viable epidermis by electron microscopy, suggesting that minimal nanoparticle penetration occurs through the human epidermis.
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Crit Rev Toxicol. 2007 Mar; 37 (3):251-77.
Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety.
Nohynek GJ, Lademann J, Ribaud C, Roberts MS.
Many modern cosmetic or sunscreen products contain nano-sized components. Nanoemulsions are transparent and have unique tactile and texture properties; nanocapsule, nanosome, noisome, or liposome formulations contain small vesicles (range: 50 to 5000 nm) consisting of traditional cosmetic materials that protect light-or oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic research suggests that vesicle materials may penetrate the stratum corneum (SC) of the human skin, but not into living skin. Depending on the physical/chemical properties of the ingredient and the formulation, nano-sized formulations may enhance or reduce skin penetration, albeit at a limited rate. Modern sunscreens contain insoluble titanium dioxide (TiO(2)) or zinc oxide (ZnO) nanoparticles (NP), which are colorless and reflect/scatter ultraviolet (UV) more efficiently than larger particles. Most available theoretical and experimental evidence suggests that insoluble NP do not penetrate into or through normal as well as compromised human skin. Oral and topical toxicity data suggest that TiO(2) and ZnO NP have low systemic toxicity and are well tolerated on the skin. In vitro cytotoxicity, genotoxicity, and photogenotoxicity studies on TiO(2) or other insoluble NP reporting uptake by cells, oxidative cell damage, or genotoxicity should be interpreted with caution, since such toxicities may be secondary to phagocytosis of mammalian cells exposed to high concentrations of insoluble particles. Caution needs to be exercised concerning topical exposure to other NP that either have characteristics enabling some skin penetration and/or have inherently toxic constituents. Studies on wear debris particles from surgical implants and other toxicity studies on insoluble particles support the traditional toxicology view that the hazard of small particles is mainly defined by the intrinsic toxicity of particles, as distinct from their particle size. There is little evidence supporting the principle that smaller particles have greater effects on the skin or other tissues or produce novel toxicities relative to micro-sized materials. Overall, the current weight of evidence suggests that nano-materials such as nano-sized vesicles or TiO(2) and ZnO nanoparticles currently used in cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP may have properties that warrant safety evaluation on a case-by-case basis before human use.
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J Invest Dermatol. 2007 Jul;127(7):1701-12.
Penetration of metallic nanoparticles in human full-thickness skin.
Baroli B, Ennas MG, Loffredo F, Isola M, Pinna R, López-Quintela MA.
The potential and benefits of nanoparticles in nanobiotechnology have been enthusiastically discussed in recent literature; however, little is known about the potential risks of contamination by accidental contact during production or use. Although theories of transdermal drug delivery suggest that skin structure and composition do not allow the penetration of materials larger than 600 Da, some articles on particle penetration into the skin have been recently published. Consequently, we wanted to evaluate whether metallic nanoparticles smaller than 10 nm could penetrate and eventually permeate the skin. Two different stabilized nanoparticle dispersions were applied to excised human skin samples using vertical diffusion cells. At established time points, solutions in receiving chambers were quantified for nanoparticle concentration, and skin was processed for light transmission and electron microscope examination. The results of this study showed that nanoparticles were able to penetrate the hair follicle and stratum corneum (SC), occasionally reaching the viable epidermis. Yet, nanoparticles were unable to permeate the skin. These results represent a breakthrough in skin penetration because it is early evidence where rigid nanoparticles have been shown to passively reach the viable epidermis through the SC lipidic matrix.
Comment: Particles in this study are <10nm in size. Particles in Intelligent Suncare products are an average of 30nm with virtually no particles smaller than 19nm.
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Exogenous Dermatology 2003;2:23-27
Attenuation of Surfactant-Induced Interleukin 1-alpha Expression by Zinc Pyrithione
Raphael Warren, James R. Schwartz, Linda M. Sanders, Prem S. Juneja
Winton Hill Technical Center and Sharon Woods Technical Center, Procter & Gamble Co., Cincinnati, Ohio, USA
Background: Dandruff is believed to be a fungus-mediated disease which responds to the topical delivery of antifungal agents. Although the primary causative factor is fungus related, distal events include an inflammatory cascade that eventually expresses itself as corneocyte flakes. The most common vehicle for dandruff treatment includes surfactants (i.e. shampoos), which as a chemical group have the potential to promote dermatitis.
Objective: To evaluate the effect of antidandruff agents and antimicrobials on the potential contact irritancy of surfactants.
Methods: Excretion of interleukin 1 by human skin equivalent cultures was measured after topical application of test materials.
Results: Zinc pyrithione specifically reduces surfactant-induced expression of interleukin 1 . Neither its sodium salt nor other antimicrobial/antifungal agents had a similar effect.
Conclusion: These data suggest that in addition to its known antifungal activity, zinc pyrithione may provide an additional benefit by reducing the potential irritancy of surfactant vehicles.
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J Surg Res. 1991 Feb;50(2):101-5.
Enhancement of re-epithelialization with topical zinc oxide in porcine partial-thickness wounds.
Agren MS, Chvapil M, Franzén L.
Department of Pathology, Faculty of Health Sciences, Linköping, Sweden.
We investigated the effect of locally applied zinc on the healing of partial-thickness skin wounds in the domestic pig using two zinc compounds (zinc oxide and zinc sulfate) in two different vehicles (a gauze compress and a collagen sponge). The rate of re-epithelialization was determined morphometrically 48 and 64 hr after infliction of standardized square wounds (4.8 cm2 and 400-microns deep) with an electrokeratome. Zinc oxide in gauze significantly (P less than 0.05) increased re-epithelialization of the wounds (33% more epithelialized than control wounds after 64 hr) and in collagen sponge (76% more epithelialized than control wounds after 64 hr). Zinc sulfate had no such stimulatory effect at any dosage or vehicle used. Our results show that topical zinc oxide enhances re-epithelialization of partial-thickness wounds in nutritionally balanced pigs and that the mode of delivery of zinc is probably critical for achieving the beneficial healing effect of zinc.
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