engineered inorganic nanoparticles and cosmetics - beautyjournaal

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Copyright © 2010 American Scientific PublishersAll rights reservedPrinted in the United States of America

Journal ofBiomedical Nanotechnology

Vol. 6, 408–431, 2010

Engineered Inorganic Nanoparticles and Cosmetics:Facts, Issues, Knowledge Gaps and Challenges

Johann W. Wiechers1�∗ and Ndeke Musee21Independent Consultant for Cosmetic Science, JW Solutions, Gasthuispolderweg 30, 2807 LL Gouda, The Netherlands

2CSIR Natural Resources and the Environment, P.O. Box 395, Pretoria 0001, South Africa

The cosmetic industry is among the first adaptors of nanotechnology through the use of engineerednanoparticles (ENPs) to enhance the performance of their products and meet the customers’ needs.Recently, there have been increasing concerns from different societal stakeholders (e.g., govern-ments, environmental activist pressure groups, scientists, general public, etc.) concerning the safetyand environmental impact of ENPs used in cosmetics. This review paper seeks to address the twinconcerns of the safety of cosmetics and the potential environmental impacts due to the constituentchemicals—the ENPs. The safety aspect is addressed by examining recently published scientificdata on the possibility of ENPs penetrating human skin. Data indicates that although particulartypes of ENPs can penetrate into the skin, until now no penetration has been detected beyondthe stratum corneum of the ENPs used in cosmetics. Yet, important lessons can be learned fromthe more recent studies that identify the characteristics of ENPs penetrating into and permeatingthrough human skin. On the part of the environmental impact, the scientific literature has very lim-ited or none existent specific articles addressing the environmental impacts of ENPs owing to thecosmetic products. Therefore, general ecotoxicological data on risk assessment of ENPs has beenapplied to ascertain if there are potential environmental impacts from cosmetics. Results includesome of the first studies on the qualitative and quantitative risk assessment of ENPs from cosmeticsand suggest that further research is required as the knowledge is incomplete to make definitiveconclusions as is the case with skin penetration. The authors conclude that the cosmetic industryshould be more transparent in its use of nanotechnology in cosmetic products to facilitate realisticrisk assessments as well as scientists and pressure groups being accurate in their conclusionson the general applicability of their findings. Transparency in cosmetics needs nanotechnology, butnanotechnology in cosmetics also needs transparency � � �

Keywords: Cosmetics, Nanoparticles, Nanotechnology, Nanowastes, Public Concern, RiskAssessment, Size Dependency, Skin Penetration, Sunscreens, Transparency,Titanium Dioxide, Topical Application, Waste Management, Zinc Oxide.

CONTENTS

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4081.1. Defining Nanoparticles in a Cosmetic Context . . . . . . . . 4091.2. Uses of ENPs in Cosmetics . . . . . . . . . . . . . . . . . . . . 4101.3. Cosmetic ENPs and Safety Concerns . . . . . . . . . . . . . . 4101.4. Cosmetic ENPs and the Environment . . . . . . . . . . . . . . 411

2. Skin Penetration of ENPs . . . . . . . . . . . . . . . . . . . . . . . . 4122.1. Pre-to 2007 Studies . . . . . . . . . . . . . . . . . . . . . . . . . 4122.2. Post 2007 Studies . . . . . . . . . . . . . . . . . . . . . . . . . . 413

3. Environmental Risk Assessment of ENPs Used in Cosmetics . . 4173.1. Waste Management: Nanowastes from

Cosmetic Products . . . . . . . . . . . . . . . . . . . . . . . . . . 4173.2. Environmental Exposure Pathways . . . . . . . . . . . . . . . 4183.3. Environmental Risk Assessment of

Cosmetics ENPs . . . . . . . . . . . . . . . . . . . . . . . . . . . 418

∗Author to whom correspondence should be addressed.

3.4. Risk Assessment of ENPs . . . . . . . . . . . . . . . . . . . . . 4204. Challenges for the Future . . . . . . . . . . . . . . . . . . . . . . . . 427

Appendix A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428References and Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . 429

1. INTRODUCTION

Nanotechnology has found wide applications in diversecommercial products (cosmetics, paints, coasting, textiles,etc.) and industrial applications, and this trend is expectedto continue into the future. While the benefits of nano-technology are beyond debate, concurrently to its growth,there are increasing concerns raised regarding safety andenvironmental impacts of this rapidly emerging technol-ogy. One of the early industrial sectors to use engineered

408 J. Biomed. Nanotechnol. 2010, Vol. 6, No. 5 1550-7033/2010/6/408/024 doi:10.1166/jbn.2010.1143

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Wiechers and Musee Engineered Inorganic Nanoparticles and Cosmetics: Facts, Issues, Knowledge Gaps and Challenges

nanoparticles (ENPs) to enhance product performance andmeet the customer needs is the cosmetic industry. There-fore, this critical review paper consists of four partsprimarily focusing on issues, facts, identification of knowl-edge gaps and challenges with respect to real or perceivedrisks of ENPs used in cosmetics, and also propose the wayforward in this industrial sector.First, we define the term engineered nanoparticles

(ENPs) in the context of cosmetic applications. In addi-tion, a description of the ENPs used in cosmetics and theassociated concerns raised by diverse stakeholders suchas regulators, governments, civil society, and general pub-lic concerning the use of these particles in cosmetics aresummarized. The issues relate to the skin penetration ofENPs into and through human skin as well their even-tual environmental impact after their use or during dis-posal. Second, the second section highlights the scientificfacts relating to the skin penetration of ENPs used in cos-metics. Next, the third section deals with aspects relatedto the environmental impact of ENPs used in cosmet-ics, particularly during the application and disposal lifecy-cle phases. The fourth section provides the views of theauthors towards these issues and offers some suggestionson the way forward with special emphasis on the futureresearch directions.

1.1. Defining Nanoparticles in a Cosmetic Context

Nanoparticles (NPs) are classified as natural, incidental, orengineered. Natural NPs occur naturally, and have been

Johann W. Wiechers did a Ph.D. in transdermal drug delivery at the University ofGroningen, The Netherlands. In 1989, he moved to the UK to start a research group inUnilever Research working on the dermal delivery of cosmetics. In 1995, he joined Uniqemain The Netherlands as their Skin R&D Director leading various skin research projects withacademics. In 2007, he started his own company, JW Solutions, where he works as an inde-pendent consultant for cosmetic science, focussing on the skin penetration of active ingre-dients and API from topical formulations. At the same time, he was appointed as VisitingProfessor at the University of London, The School of Pharmacy, Brunswick Square, London.He serves on the editorial board of many journals related to cosmetic science and was Pres-ident of the IFSCC, the International Federation of the Societies of Cosmetic Chemists, afederation in which 14,500 cosmetic scientists from all over the world are united.

Ndeke Musee has been a Senior Researcher at the CSIR, South Africa, since July 2007. Heis a registered professional scientist with the South African Council for Natural ScientificProfessions, and holds a Ph.D. in Chemical Engineering Science from the University ofStellenbosch. He is credited for initiating research on nanotechnology risk assessment inpartnership with the Department of Science and Technology, as well as for forming thefirst research group in this field in South Africa, at the CSIR. He is the former chairand organizing convener of the First and Second South Africa National Workshops onNanotechnology Risk Assessment held in April 2009 and July 2010, respectively. Ndeke isa member of the Technical Committee on the ISO TTC 229 working group, a member ofthe National Nanotechnology Health, Safety and Environment Advisory Committee—all inSouth Africa—and supervises several postgraduate students.

in the environment for long time. Examples include vol-canic systems and mineral composites.1 Incidental NPs areunintentionally generated from manmade industrial pro-cesses or as a consequence of engine pollution, e.g., dieselexhaust, coal combustion and welding fumes.2 NPs fromunintentional sources comprise of soot, black or elemen-tal carbon, metal sulfide nanoclusters, ammonium, nitrate,trace metals, etc., mainly characterized by polydispersion,heterogeneity and irregular or regular shapes.1

Engineered nanoparticles (ENPs) are created either top-down (via milling) or bottom-up (via crystal growth)3 andcharacterized by monodispersion, homogeneity and reg-ular shapes (e.g., tubes, rings, cylindrical or spheres).4

In recent years, technological advancement has resulted ina dramatic growth of the incorporation of ENPs in dif-ferent product types to enhance their performance. Thisis because of their exceptional physicochemical propertiessuch as a large surface area as about 40–50% of the atomsare on the surface besides enhanced optical, magnetic andelectrical conductivity properties. In summary, whethernatural, incidental or engineered NPs, the nanoscale mate-rials broadly fall into four categories, namely:(i) metal oxides like zinc and titanium oxides widely usedin ceramics, chemical polishing agents, scratch-resistantcoatings, cosmetics and sunscreens;(ii) nanoclays which are naturally occurring plate-likeclay particles that strengthen or harden materials or makethem flame retardant;(iii) nanotubes generically carbon-based nanomaterialsused in coatings to dissipate or minimize static electricity

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Engineered Inorganic Nanoparticles and Cosmetics: Facts, Issues, Knowledge Gaps and Challenges Wiechers and Musee

(e.g., in fuel lines, in hard disk handling trays, or in auto-mobile bodies to be painted electrostatically); and(iv) quantum dots mostly exploited in exploratorymedicine, or in the self-assembly of nanoelectronicstructures.

The regular shapes of TiO2 and ZnO render them usefulnanoscale materials for cosmetics application. Their twomost important aspects are the absolute size of the NPsand their surface properties which determine their efficacyas a protective sun filter. Particle size determines the rela-tive surface area. The surface area of a cubic centimeter ofa solid material is 6 cm2, whereas that of a cubic centime-ter of 1 nm particles in an ultrafine powder is 6,000 m2,literally a third larger than a football field.4 Surface areais important because most chemical reactions involvingsolids happen at their surfaces, where the chemical bondsare incomplete. On the other hand, surface properties ofmetal oxides like TiO2 are unique.5

Cosmetics and sunscreens products are currently fabri-cated using different ENPs such as metal NPs (silver, Ag),metal-oxides NPs (titanium oxide, TiO2; zinc oxide, ZnO;iron oxide, Fe2O3), and carbon-based NPs (fullerenes)6�7

mainly as sun filters and are regularly shaped. However,while the benefits of using diverse ENPs in products inreference to market differentiation and functionality arebeyond debate, their use potentially introduces challengesin terms of environmental management. This is becausethe use of different ENPs introduces complexity in rela-tion to the fate, transport, behaviour, and ecotoxicologicaleffects of each NP in different environmental organisms.As a result, use of nanoscale materials renders risk man-agement of cosmetic-based waste streams challenging.This aspect will be examined in detail in Section 3.

1.2. Uses of ENPs in Cosmetics

TiO2 and ZnO are examples of the so-called inorganic or‘physical’ sunfilters, whereas organic or ‘chemical’ sun-filters also exist. The former provide a broad spectrumprotection against UVA and UVB, whereas the latter areusually classified as either UVB or UVA filters. The dif-ference between TiO2 and ZnO is that the former isoptimized for UVB attenuation to give protection fromsunburn, whereas the later is optimized for UVA attenu-ation to give protection from UV-induced aging. As thesun protection factor (SPF) is related to UVB protection,titanium oxide is more effective in terms of SPF at a givenconcentration.8

Figure 1 depicts the light attenuation properties for TiO2

of various mean particle sizes. Pigmentary TiO2 with acrystal size of about 220 nm gives UV protection but alsoattenuates visible light, and hence appears white on theskin. Reducing the crystal size increases UV attenuationand reduces visible attenuation. The optimum particle sizefor UVB and UVA attenuation with good transparency

290 340 390 440 490 540

Wavelength (nm)

Atte

nuat

ion

of U

V

20 nm

50 nm

100 nm

220 nm

UVB UVA Visible

Fig. 1. UV/visual attenuation spectra for various particle sizes of tita-nium dioxide. Modified from Ref. [8].

in the visible region ranges between 40 and 60 nm.To achieve complete visible transparency the particle sizecan be reduced even further to about 20 nm; however, sucha small particle size provides little UVA or UVB attenua-tion and is therefore very ineffective as a sunscreen.8

Modern cosmetic sun protection products use bothorganic and inorganic sunfilters, but the choice dependson the final product and application. Whereas organic sun-filters are easier to formulate with a high efficacy at lowconcentrations, cocktails of different sunfilters are requiredto obtain high SPF’s. High concentrations of multiple fil-ters are necessary to achieve such high levels which maycreate formulation problems with the solid filters that aredifficult to solubilize. Certain organic sunfilters decay onexposure to UV light. The inorganic sunfilters are, how-ever, photostable and high SPF’s can be obtained with asingle filter (TiO2).

Both ZnO and TiO2 are supplied as powders that havetwo disadvantages. Powders are generally difficult to for-mulate but dispersions also exist that make these filtersmuch easier to incorporate into cosmetic formulationswithout loss of efficacy due to coagulation of the activeprinciple. Second, inorganic filters may leave a white shineon the skin. However, this latter shortcoming is addressedthrough controlling two parameters, particle size and parti-cle size distribution of the organic filter. When both param-eters are optimized and controlled, transparency can beobtained without loss of sun protection efficacy as mea-sured via the SPF, and illustrated in Figure 2. As a con-sequence, the use of nanosized sun protective ENPs hasrisen dramatically over the last decade.

1.3. Cosmetic ENPs and Safety Concerns

The use of these ENPs in cosmetics led to rising safetyconcerns. “In one of the most dramatic failures of regula-tion since the introduction of asbestos, corporations aroundthe world are rapidly introducing thousands of tons ofnanomaterials into the environment and onto the faces and

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Fig. 2. Different degrees of skin transparencies are obtained by opti-mizing and controlling particle size and particle size distribution. Equalamounts of two formulations were applied on the skin that contained thesame level of titanium dioxide (50% solids). The two forms of titaniumdioxide differ in particle size and particle size distribution. On the left,the most frequently seen particle size is 35 nm whereas on the right, thisis 30 nm with a much narrower particle size distribution. Picture usedwith permission of Julian Hewitt, Croda Chemicals UK.

hands of hundreds of millions of people, despite the grow-ing body of evidence indicating that nanomaterials canbe toxic for humans and the environment.” This sentenceis the first in an executive summary of the May 2006Friends of the Earth report “Nanomaterials, sunscreens andcosmetics: small ingredients, big risks.”9 Also, it is thefirst sentence of the introduction chapter of the report,and was repeated on the back cover of the same report.Based on this opening and closing statement, one wouldbe inclined to think that there would be something funda-mentally wrong with nanotechnology.Indeed, epidemiological studies consistently show that

increases in atmospheric particulate concentrations lead toshort-term increases in morbidity and mortality. Inhalationis the most significant exposure route for unintentionally-generated NPs, of which road transport (60%) and com-bustion processes (23%) are the major sources.10 Asdescribed above, the sunscreen actives in nanoparticulateformat are intentionally made ENPs that are much moreregular in shape, and follow a different route of entryinto the body. The exposure of intentionally manufacturedENPs merits research attention to elucidate the modes ofaction and mechanisms as was previously done for theunintentionally produced NPs. Notably, the skin and inges-tion must be considered in addition to inhalation as alter-native routes of uptake for ENPs used in cosmetics. Theskin seems logical as a port of entry into the body for cos-metics whereas ingestion may seem a bit odd but cannot beignored. This is because if NPs are not fully absorbed intothe skin, they may therefore end up in wastewater wherethey can be incorporated into organisms and eventuallyreach humans through the food chain via biomagnificationand bioaccumulation processes. In addition, it may happenthat the user of cosmetic products may touch the mouthwhich could introduce a certain degree of risk throughingestion as well. However, depending on quantities thismay be an insignificant route of exposure and thereforeconstitute only a minor risk.

The Friends of the Earth are of course right when statingthat ENPs can be toxic for humans and the environmentbecause every chemical can be toxic. Toxicology is onlya matter of dose as expressed by Paracelsus (1493–1541):“All substances are poisons—there is none which is nota poison. The right dose differentiates a poison from aremedy.” The appropriate question is therefore not whetherthese ENPs can be toxic but whether they are toxic atthe concentrations mankind is exposed to intentionally ornon-intentionally. Risk of ENPs is a function of the haz-ard and the degree of exposure to the receptor population.Section 2 presents a discussion on the quantification ofENPs risk in the context of skin penetration.

1.4. Cosmetic ENPs and the Environment

To contextualize the discussions on the risks of ENPs usedin cosmetics to the environment, it is essential to define theproblem boundaries. Presently there are numerous ENPsused for manufacturing different types of nanoproductsand in diverse industrial applications. However, in thispaper, our focus is on ENPs commonly used in cosmet-ics from an environmental risk assessment perspective.The commonly used ENPs in cosmetics consist of TiO2,ZnO, fullerenes, Fe2O3, and Ag. Defining the problemboundaries contextualizes the extent to which the nano-ecotoxicological data currently available in the literaturecan be meaningfully used in assessing the potential risksof ENPs from cosmetic industry-based products and/orwaste streams to different environmental receptor organ-isms such as plants, fungi, sediment-dwelling organisms,and invertebrates.The main sources of ENPs into the environment include

incidental and accidental releases from industrial produc-tion facilities, liquid and solid waste streams from indus-tries and households, un-removed ENPs from wastewatertreatment plants (WWTP), agricultural application ofmunicipal sludge as well as incidentals during transporta-tion. The effects of industrial sources are likely to be local-ized, easy to control (e.g., handling procedures, preventionof leakages, waste conditioning, etc.), and unlikely to beextensive in nature, and will not be considered in detailsin this article. However, the scenario is different if oneconsiders the potential environmental exposure of ENPsfrom cosmetics particularly during the application and dis-posal phases. The reason being, during these two life-cycle phases the releases into the environment are expectedto be high and widespread over large areas in differentenvironmental systems, mainly to water and soil compart-ments. Thus, if risk assessment and appropriate associatedmitigating mechanisms remain unaddressed—wide spreadENPs in the environment may cause long-term unintendedeffects over large areas—, this will result in situations thatare costly and laborious to remediate.


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2. SKIN PENETRATION OF ENPs

Whereas it is impossible to assess the absolute safety ofsomething (after all, one cannot demonstrate the presenceof an absence), it is possible to measure whether or not achemical or in this case an ENP penetrates the skin. Here,again, the same proviso needs to be made, namely that onecannot demonstrate the absence of skin penetration, onlythe presence of skin penetration. Also, one needs to definewhat skin penetration means in relation to the potentialtoxicology of a nanoparticle. After all, if TiO2 is depositedonto the skin surface where it attenuates UVB radiation viascattering and absorption, it has been effectively deliveredfrom a cosmetic efficacy point of view. Yet, from a toxico-logical point of view where the ENP may interact with theliving tissue in a harmful manner, it has not been deliveredat all, as the viable tissues have not been reached. Skindelivery of ENPs in the context of toxicology is thereforedefined as ENPs reaching the viable epidermis and dermis.The lack of delivery of ENPs to the viable tissues doesnot imply safety as it may be that the presence of NPscould not be demonstrated due to the lack of sensitivity ofthe employed analytical methods. As we will see below,visualization techniques are therefore most suitable as thesensitivity is the same in all tissue areas, i.e., if a singleENP can be seen in the stratum corneum, the dead layer onthe top of the skin, the method is sensitive enough to visu-alise ENPs, but they were not detected in the deeper, livinglayers of the skin, the viable epidermis and the dermis.

2.1. Pre-to 2007 Studies

Many experimental studies investigating the skin deliveryof ENPs have been reported in the scientific literature andhave been reviewed recently.11–13 The extensive referencelist of the by now already classic Grey Goo on the Skinreview on the use of ENP in cosmetic and sunscreen safetyof 2007 lists some 30 articles that discuss the skin pen-etration of solid ENPs in one way or another.11 Papersdescribing the skin penetration of more flexible structuressuch as liposomes or uptake into isolated cells were dis-carded, but those describing the skin penetration of solidlipid nanoparticles (SLNs) were included. The majority ofthese papers were discussed herein in detail, and almostall led to the same conclusion.ENPs do penetrate the stratum corneum where they can

be visualized but do not penetrate deeper into the viablelayers of the epidermis and the epidermis. At the sametime, the infundibulum (the opening around the hair folli-cle where sebum is located) often acts as a reservoir andNPs accumulate there till they are removed with the sebumflow. Only a few papers suggest that skin penetration ofNPs does occur, but in those cases, the observed skin pen-etration could be explained from the experimental or theanalysis methods used.11 Some investigators subsequentlyrevised their methodology to overcome these artifacts and

found no skin penetration beyond the stratum corneum inthe modified experiments.12�13 But it needs to be stressedthat almost all these papers discussed the skin penetrationof microfine TiO2 or ZnO, whereas skin penetration ofother ENPs was far less extensively studied, with the onlyexception of quantum dots, that are much smaller thanmicrofine TiO2 and ZnO.The main gaps in our knowledge on the skin penetration

of ENPs at the end of 2008 were elegantly expressed byBaroli, when she wrote that “Extensive exposure of skin tothese nanotechnological products has raised the questionas to whether ENPs could penetrate skin, be eventuallyabsorbed systemically, and more importantly be respon-sible for acute/chronic and/or local/systemic side effects.This concern is not hypothetical when one considers that(i) skin is nanoporous at the nanoscale,(ii) orifices of hair follicles and glands open on skin sur-face, providing alternative routes of entrance, and(iii) in everyday life skin may be damaged by deter-gent exposure, scratches, hydration or dryness, sunburn, orpathological states.”14

This knowledge gap analysis resulted from earlier studyfindings of Baroli and colleagues15 investigating whethersuperficially modified iron-based ENPs—not designed forskin absorption—but whose dimensions were compatiblewith those of skin penetration routes were able to penetrateand perhaps permeate the skin. Experiments were carriedout with healthy female abdominal skin samples clampedinto vertical diffusion cells, and exposed to ENPs for amaximum of 24 hours.Two different ENP formulations were tested. The first

one consisted of �-maghemite (Fe2O3) ENPs, coatedwith tetramethylammonium hydroxide (TMAOH), and dis-persed in an aqueous solution of TMAOH (TMAOH-NPs). The second formulation composed of iron (Fe)ENPs, coated with sodium bis(2-ethylhexyl) sulfosucci-nate (AOT) dispersed in an aqueous solution rich in AOT(AOT-NPs). ENP characterization revealed the TMAOH-NPs had a size of 6�9± 0�9 nm, and an isoelectric pointat 6.3. In contrast, AOT-NPs were not homogeneous insize, even though 51.1% of these ENPs had a diameterof 4�9± 1�3 nm. Results showed that ENPs did not crossthe skin, but nonetheless were able to penetrate into it.Penetration occurred through the lipid matrix of the stra-tum corneum and hair follicle orifices, allowing ENPs toreach the deepest layers of the stratum corneum, the stra-tum granulosum, and hair follicles. Only in exceptionalcases, the ENPs were found in the viable epidermis (seeFig. 3).15

Independently from the Baroli group, another Italiangroup of investigators studied the skin penetration of AgENPs through intact and damaged human skin, using Franzdiffusion cells. Their data showed that Ag NPs absorp-tion through intact skin was very low but detectable, andthat there was an appreciable increase in permeation usingdamaged skin.16


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Fig. 3. Light transmission microscopy of hematoxylin-stained skinspecimens exposed to NPs. This staining procedure allows coloring ofcell nuclei of the viable epidermis (VE) and some cells of the dermis(D) in a darker blue and their cytoplasms in a lighter blue while thestratum corneum (SC) and most of the dermis remain faint. Brownishdeposits on and between the lamellae of a swollen stratum corneum (a, c;black arrows) can be clearly seen, and less clearly some smaller brownishdeposits in the stratum granulosum of the viable epidermis (a, b; yel-low squares). Melanin granules are clearly recognizable (b, c, and muchless in a; magenta arrows) in the stratum basale of the viable epider-mis. Bar = 50 �m. Reproduced with permission from [15], B. Baroliet al., Penetration of metallic nanoparticles in human full-thickness skin.J. Invest. Dermatol. 127, 1701 (2007). © 2007, Nature Publishing Group.

Concurrently, other studies emerged in the literatureindicating absence of skin penetration by ENPs. Gontieret al.17 performed a comparative study using high reso-lution transmission electron microscopy (HRTEM), scan-ning transmission ion microscopy (STIM) combined withRutherford backscattering spectrometry (RBS), and par-ticle induced X-ray emission (PIXE) on ultra-thin andthin cross-sections of various skin samples (porcine skin,healthy human skin, human skin grafted on a severecombined immuno-deficient mouse model). In each skinsample type, they applied topically various formulationscontaining TiO2 ENPs with primary particle sizes rangingfrom 20–100 nm. Whereas the HRTEM and STIM/PIXEimages revealed clear differences—mainly related to thedifferent thickness of the cross-sections—they unambigu-ously showed that penetration of TiO2 ENPs was restrictedto the topmost 3–5 corneocyte layers of the stratumcorneum. Sceptics might argue that only human skinin vivo should be used to assess the skin penetration ofsunscreen ENPs. Another 2008 study using multiphotonmicroscopy (MPM) imaging with a combination of scan-ning electron microscopy (SEM) and an energy-dispersiveX-ray (EDX) technique also showed that, in humansin vivo, ZnO ENPs stayed in the stratum corneum, and

accumulated in into skin folds and/or hair follicle roots ofhuman skin.18

This raises the question on what changed to cause cer-tain ENPs to penetrate, albeit seemingly only in minorquantities,15�16 whereas others do not penetrate at all?17�18

First, the size of the skin-penetrating ENPs was signifi-cantly smaller than those widely used in cosmetics (TiO2

and ZnO). Second, although all ENPs mentioned abovewere metallic, the penetrating ENPs used other elementthan titanium17 or zinc,18 namely iron15 and silver.16 Andthird, the formulations of iron and silver ENPs were rad-ically different from a cosmetic formulation, and demon-strated to have an effect on skin barrier function. Detergentproperties of the AOT rich aqueous solution in which AOT-NPs were dispersed might have been the principle causeof AOT-NP penetration.14�15 This led to the identificationof the following knowledge gaps with respect to the skinpenetration of ENPs:(1) What do we know about the potential skin penetrationof very small ENPs, i.e., those below 10 nm?(2) What are the effects of real-life conditions such as UVradiation, abrasion, skin damage, etc. on the skin penetra-tion of ENPs? and finally(3) Why is the use of ENPs as skin delivery systems advo-cated if they do not penetrate into skin?

2.2. Post 2007 Studies

Not surprisingly, most experimental studies published in2008 and 2009 focused on addressing one or more of theabove identified outstanding issues. Although we do notpretend to claim presentation of a comprehensive reviewof the available scientific literature regarding the subjectin this paper, the majority of the newly published paperswill be discussed to identify whether the knowledge gapsat the end of 2007 have been sufficiently addressed. Thesection will close by presenting a brief on remaining ornew gaps concerning skin penetration of ENPs.

2.2.1. Skin Penetration of the Smaller ENPs, inParticular Quantum Dots

The controversy on whether or not ENPs can penetratebeyond the stratum corneum started with the publicationof a paper by Ryman-Rasmussen et al.19 Their findingssuggested that quantum dots (QDs) may penetrate into theepidermis or dermis of intact porcine skin. QDs are nano-crystals used for imaging purposes in medical diagnostics(and are not used in cosmetics). They have a metallic coresurrounded by an inorganic shell coating. Organic coat-ings may be added to the surface of the shell to providea charge, and to allow the binding of antibodies in orderto achieve greater biocompatibility, solubility, or bind tospecific receptors in cells or tissue.Two types of QDs were used in this study with three

different coatings: spherical shaped particles with a size


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of 4.6 nm, and ellipsoid shaped particles measuring 6 nm(minor axis) and 12 nm (major axis). Their coatings wereanionic, neutral or cationic. It should be kept in mind thatthe hydrodynamic diameter of these QDs was larger dueto solvation effects especially for the neutral coating. Con-focal microscopy revealed that the smaller, spherical QDspenetrated the stratum corneum of freshly dermatomed pigskin and localized within the epidermal and dermal lay-ers by 8 hours irrespective of their surface coating (seeFig. 4). Similarly, the larger ellipsoid QDs with a neu-tral or cationic coating also localized within the epidermallayers by 8 hours.No penetration of the larger QDs with the anionic coat-

ing was evident until 24 hours, at which time localiza-tion in the epidermal layers was observed. The authors

Fig. 4. Confocal microscopy of skin treated for 8 h with PEG, PEG-amine (NH2), or carboxylic acid (COOH)-coated quantum dots 565 (QD 565;spherical quantum dots with a core/shell diameter of 4.6 nm). Coatings are noted at the top of each column. Top row: confocal-differential interferencecontrast (DIC) channel only allows an unobstructed view of the skin layers. Middle row: confocal-DIC overlay with the quantum dot fluorescencechannel (green) shows quantum dot localization within the skin layers. Arrows indicate the presence of quantum dots in the epidermis or dermis. Bottomrow: fluorescence intensity scan of quantum dot emission. Quantum dots 565 are localized in the epidermal (PEG and COOH coatings) or dermal (NH2coating) layers by 8 h. All scale bars (lower right corners) are 50 �m. Reproduced with permission from [19], J. P. Ryman-Rasmussen et al., Penetrationof intact skin by quantum dots with diverse physicochemical properties. Toxicol. Sci. 91, 159 (2006). © 2006, Oxford University Press.

concluded that QDs of different sizes, shapes, and sur-face coatings can penetrate intact skin at an occupationallyrelevant dose within the span of an average-length workday. This suggested that “skin is surprisingly permeable tonanomaterials with diverse physicochemical properties andmay serve as a portal of entry for localized, and possiblysystemic, exposure of humans to quantum dots and othernanoscale materials.”19

Nohynek et al.11 warned that these studies were con-ducted with QDs being applied in quite alkaline solutions(pH 8.3 or 9.0), which could result in reduced barrier func-tion. But evidence for increased skin penetration at thispH is limited. In 1965, Bettley already did not find a cor-relation of permeation with pH,20 whereas a recent paperby Sznitowska et al.21 confirmed this conclusion, that up


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to pH 11.0 no change in the penetration of hydrocortisoneand testosterone was found. The same group, therefore,repeated the experiments in different ways to overcomethis criticism.22 They used the same small spherical andlarger ellipsoid QDs but only those with the anionic coat-ing that in the previous study localized mainly in theepidermis by 8 hours (small spherical QDs) or did notpenetrate until 24 hours (larger ellipsoid QDs).19

The objective of the new study was to investigatewhether flexion, tape stripping and abrasion could causean increase in the penetration of QDs of different sizes andshapes. Using rat skin instead of pig skin (as used in thefirst study), it was found that on intact skin the penetrationof both QDs was primarily limited to the uppermost stra-tum corneum layers. Barrier perturbation by tape strippingdid not cause penetration, but abrasion with sandpaperallowed the quantum dots to penetrate deeper into the der-mal layers. Occasionally, retention of QDs was observedin hair follicles in abraded skin. Penetration of ENPs notonly occurred on the surface of the stratum corneum layersor within the stratum corneum layers; they also penetratedfurther down the skin with skin flexing.22

A third publication by the North Carolina group aimedto summarize the factors that influence the skin penetra-tion of QDs. Monteiro-Riviere and Riviere23 compared theresults of previous studies obtained on porcine and humanskin and observed that QDs permeated through porcineskin but not through human skin,23 a species differencehardly observed for the skin penetration of chemicals.24

With respect to size, the only larger sized ENPsdescribed in the literature to permeate skin until now areblock copolymer ENPs.25 The 40 nm and 130 nm sizedENPs were tested on both hairy and hairless guinea pigskin in Franz diffusion cells. In hairy guinea pig skin,the permeation of minoxidil incorporated in 40 nm ENPswas 1.5-fold higher in the epidermal layer and 1.7-foldhigher in the receptor solution than that of the 130 nmENPs. ENP size dependency on the permeation behaviorof minoxidil was not observed for hairless guinea pig skineither in the epidermal layer or the receptor fluid.25 Thisposes the question whether the origin of the skin (hairlessor hairy guinea pig skin vs. human skin) is at the basis ofthe skin penetration or the size of these ENPs. It could berelated to species-dependent variables such as hair follicledensity. This is in line with the observation of Zhang andMonteiro-Riviere who also suggested that QD penetrationnot only depended on ENP size and charge, but also onspecies differences and hair follicle density.22

2.2.2. Skin Penetration by ENPs UnderReal-Life Conditions

Different ‘real-life’ conditions have been investigated thatmay influence the skin penetration of ENPs, namelyUV-radiation (very relevant during sunscreen application),

mechanical stretching, flexing and massaging of the skin(relevant as many people apply sunscreens during outdoorphysical exercise), and skin damage (relevant for toxico-logical reasons as this normally reduces the barrier func-tion of the skin and users of sunscreens may have minorcuts and grazes). Additionally, there is the issue of thecomposition of the formulation, a factor well known toaffect the skin penetration of active ingredients.26 This sub-section therefore deals with external physical, mechanicaland chemical influences on the skin penetration of ENPs.The article of Mortensen et al.27 merits to be discussed

because it investigated the effect of UV radiation on thein vivo skin penetration of QDs in a mouse model. Car-boxylated QDs were applied to the skin of SKH-1 micein a glycerol vehicle with and without exposure to UVradiation. The investigators deliberately aimed to mimic asmany conditions as possible to reflect the cosmetic situa-tion. For instance, the ENPs were negatively charged likethe metal oxides used in cosmetics. This is important as thecharge affects their capability to adhere to the negativelycharged skin surface. In contrast to anionic ENPs, cationicENPs showed clear affinity for the skin surface and deliv-ered a significantly greater amount of model active intothe stratum corneum.28

The size of the QDs used by Mortensen et al.27 was∼33 nm, again in line with ENPs used in cosmetics.The skin collection and penetration patterns were eval-uated at 8 and 24 h after QDs application using tissuehistology, confocal microscopy, and transmission elec-tron microscopy (TEM) with energy dispersive analysisof X-ray (EDAX) attachment to provide elemental analy-sis spectra of samples. The investigators found a trend ofincreased penetration for both treatment conditions (8 and24 hours) with UV radiation. Under no circumstancesdid they find evidence for massive QD penetration, evenfor UV radiation-exposed mice 24 h after quantum dotapplication.27

The article caused considerable controversy. Withintwo weeks of e-publication, the Nanotechnology Indus-try Association (NIA) published a comment on thispublication29 in which they pointed out that “the size ofQDs reported in this paper corresponds to the hydrody-namic diameter, not the actual ‘physical’ diameter (5 nm).In sunscreens, however, individual nanoparticles aggregateand agglomerate to form much larger units, which are typ-ically >100 nm.”29 The NIA also argued that the in vivomodel (UV radiation exposed mice) was not representativeof the conditions encountered during the use of a sunscreenformulation.Other ‘real-life’ situations such as flexing and abra-

sion of the skin (to reflect damaged skin) on the skinpenetration of NPs were also investigated. Zhang andMonteiro-Riviere22 concluded that barrier perturbation bytape stripping did not cause skin penetration, but abrasionallowed QDs to penetrate deeper into the dermal layers.


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In a second study by the same group, Rouse et al. mea-sured the penetration of a fullerene-substituted phenylala-nine derivative of a nuclear localization peptide sequence(Baa-Lys(FITC)-NLS) through dermatomed porcine skinthat was flexed for 60 or 90 min or left unflexed (con-trol). Confocal microscopy depicted dermal penetration ofthe nanoparticles at 8 h in skin flexed for 60 and 90 min,whereas Baa-Lys(FITC)-NLS did not penetrate into thedermis of unflexed skin until 24 h (see Fig. 5).30 Skinflexed for 90 min showed evidence of dermal penetra-tion after 8 h of ENP exposure, whereas control samplesshowed evidence of fullerenes primarily localized in theepidermis and only slight amounts in the dermis after a24 h treatment. These results suggest that the action ofa flexing procedure increases the rate at which ENPs canpenetrate through the skin, as well as the amount of ENPsthat were capable of penetrating into the dermal layers ofthe skin.30 The latter is not surprising if one combines thisfinding with the statement of Wu et al.28 that their results‘confirmed an apparent affinity between the vectors and

Fig. 5. Confocal scanning microscopy images of skin dosed with Baa-Lys(FITC)-NLS for 24 h. Top row: confocal-DIC channel image shows anintact stratum corneum (SC) and underlying epidermal (E) and dermal layers (D). Middle row: Baa-Lys(FITC)-NLS fluorescence channel (green) andconfocal-DIC channel show fullerene penetration through the skin. Bottom row: fluorescence intensity scan of Baa-Lys(FITC)-NLS. All scale barsrepresent 50 �m. Reproduced with permission from [30], J. G. Rouse et al., Effects of mechanical flexion on the penetration of fullerene aminoacid-derivatized peptide nanoparticles through skin. Nano Lett. 7, 155 (2007). © 2007, American Chemical Society.

hair follicular structures’ and previous publication findingsof Lademann and co-workers where massage and flexingwere established to stimulate the opening of hair follicles,and hence, increase transfollicular delivery.31

The influence of formulation composition on the skinpenetration of ENPs to date has not been investigated thor-oughly and systematically. First, for clarity purposes wedefine what is meant by formulation influences. Two for-mulation influences can be distinguished. First, there is theinfluence of the ‘remainder’ of the formulation on the pen-etration of the ENPs, i.e., the influence of all other com-ponents besides the ENP. Second, there is the influence ofthe coating of the ENP on the penetration of the ENP. Thelatter aspect has been studied more extensively than theformer. Ryman-Rasmussen et al.19 studied three differentsurface coatings of ENPs, neutral, cationic and anionic.QDs with an anionic coating penetrated much slower intoporcine skin than those with a cationic or neutral coating,depending on the QDs size as smaller sizes did not showthis difference (see Fig. 3, showing the skin penetration


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of the smaller QDs). The reason for the difference in skinpenetration characteristics of similar ENPs having differ-ent coatings is their affinity for negatively-charged skinas explained by Wu and co-workers.28 In addition, theirtissue distribution once inside the body is influenced byENP coating. Lee et al., for instance, showed that theskin uptake of negatively charged QDs was 2 to 3-foldgreater than that of the neutral QDs.23�32 These contradic-tory results are most likely caused by other ENPs charac-teristics that remain yet to be systematically investigated.Until now, the influence of the remainder of the formula-

tion on the skin penetration of ENPs is hardly investigated.The literature reveals that some ENPs were dispersed inwater,15�33�34 others in oil/water emulsions,35�36 in non-described commercial sunscreen formulations,37 in ethanolabsolute 0.14 wt% and in diluted 1:10 synthetic sweat atpH 4.5 (to reproduce in vivo conditions),16 in commer-cial dermatological products and in pharmaceutical galenicgels,17 in synthetic sweat,38 in glycerol,27 in phosphatebuffered saline,30 in borate buffer,19�22 in 30% ethanol,25

in a mini-emulsion,28 or in caprylic/capric triglycerides.18

With such a diversity of unrelated vehicles containing dif-ferent particles with different sizes at different loadings,it is extremely difficult to make generalized conclusionson the influence of the vehicle components or dispersionmedium. Therefore, the comment by Baroli et al.15 that“processes governing the penetration of chemicals39 andparticles might not be the same” is very interesting but itremains yet to be worked out if and how it is different, letalone on how the formulation composition influences theskin penetration of ENPs into and through skin.

2.2.3. Use of ENPs as Skin Delivery Systems

The above suggests that the capability of ENPs to pen-etrate skin may depend on its chemical composition.On the one hand, ENPs containing chromium,38 silver,16

TiO2,17�35�37 and ZnO18�35�37 did not penetrate deeper than

the stratum corneum in line with the general outcome of arecent review on the skin penetration of ENPs.12 Occasion-ally, however, ENPs seemed to penetrate into the livinglayers of the skin but this could be attributed to the solubi-lization of the particles, and subsequent penetration of theassociated ions rather than the metal (cobalt and nickel38

and zinc oxide40). Yet, on the other hand, QDs with acadmium-selenide or cadmium sulfide core were shownto penetrate into the deeper skin tissues (see Fig. 4),19 aswere fullerene-based NPs.30 Consequently, certain ENPspenetrate skin whereas others don’t.There is a third category of NPs that is purpose-built

to carry drugs and actives into the skin. Some of theseare polymeric in nature25�33�36�41 but by far the majoritycomprises of lipids such as stearic acid42 or mixtures offatty acids.43�44 As these so-called solid lipid nanoparticles(SLNs) and nanostructured lipid carriers (NLCs) tend to

operate via release of their active ingredient rather thanpenetration of the lipid carriers itself, they are beyond thescope of this review and interested readers are referred tothe literature.43–45

In summary, ENPs can penetrate into the skin but untilnow, no penetration of the ENPs used in cosmetics hasbeen detected beyond the stratum corneum.

3. ENVIRONMENTAL RISK ASSESSMENTOF ENPs USED IN COSMETICS

3.1. Waste Management: Nanowastes fromCosmetic Products

Environmental management particularly with respect towaste management over many decades has remained out-side the core focus of many businesses or industrial sectorsincluding the cosmetic industry. However, the scenario hasdramatically changed over the last 30 to 40 years as gov-ernments, regulatory authorities, customers, investors andthe public in general have exerted different and increas-ing forms of pressure to force companies to consider thepotential impacts of their products and services to theenvironment.Unsurprisingly, Kumar46 recently summarized several

environmental concerns directed towards the cosmeticindustry by consumers. These included opposition to theuse of volatile organic chemicals (VOCs), protests againstuse of animals for testing, demand for the reduction ofquantities of materials used in packaging, and exaggera-tions regarding the extent to which the industry is green.Two profound examples cited pointed claims towards theindustry’s use of biodegradable packages though no recy-cling plants were in place at the time of such asser-tions, and secondly, that the cosmetic products wereozone friendly though chlorofluorocarbons (CFCs) hadbeen banned since the late 1970s.46

To the authors’ knowledge, the nanotechnology eco-nomic volume and contribution in the cosmetics is yet tobe published. Recent analysis of the cosmetic global indus-try growth trends reveal that because of increasing inno-vations and technologies capabilities the industry wouldcontinue to achieve an average global growth rate of 5%.46

Kumar46 advanced several reasons to support the view thatin the cosmetic industry such growth rates or even higherare likely to be maintained in the future. Therefore, weargue that the innovations and technologies that wouldpropel the market volume and revenues in this industryinclude the incorporation of nanotechnologies in cosmet-ics. Consequently, this will result not only in producingproducts that meet the consumers’ needs but also poten-tially increase waste streams containing ENPs that eventu-ally are released into the environment particularly duringthe application and disposal lifecycle phases.Several waste management issues in the cosmetic indus-

try are outstanding, and this merits to be addressed. In this


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paper, the focus will be to elucidate waste managementaspects related to nanoproducts because of the dramaticincrease in the use of ENPs in cosmetics. The new formsof waste streams are generically referred to as nanowastes.Presently these waste streams are non-quantified in anygiven form of products or industry mainly due to lackof data. Musee47 defined nanowaste(s) as waste stream(s)containing(i) engineered nanoparticles (ENPs), nanomaterials(NMs), or synthetic by-products with nanoscale prop-erties, generated either during production, storage anddistribution, or,(ii) waste stream(s) resulting from the end of lifespanof formerly nanotechnologically-enabled materials andproducts, or(iii) waste streams generated through the use of nanoma-terials to remove pollutants from aqueous and/or gaseouseffluents.

In this paper, we limit our focus to the first and secondparts of the nanowastes definition.Processes where nano-related waste streams are gener-

ated include production, distribution, handling, during theincorporation of NMs into bulk products, and at disposal.As mentioned earlier, waste streams generated during theapplication and disposal phases are likely major contribu-tors of ENPs dispersion from cosmetics. Though presentlythere are many cosmetics products containing ENPs in themarket, they are not viewed to generate nanowaste streams.This is attributable to the non-disclosure of informationregarding the use of ENPs in cosmetics, and/or the lackof knowledge to appreciate their presence and uniquenessfrom the current counterpart bulk waste streams.

3.2. Environmental Exposure Pathways

The environmental exposure of ENPs in sunscreens andcosmetics used for skin applications are likely to bereleased into surface waters during swimming or bathing.Also, wastes from cosmetics are disposed of through thedomestic waste management systems such as waste watertreatment plants (WWTP) and landfills (for the case of cos-metic containers and expired products). The environmentalexposure pathways of nanowastes from cosmetics are sum-marized in Figure 6. From the landfills, leachate genera-tion may cause underground water contamination. On theother hand, cosmetic products owing to their wide spreaduse may cause profound impact especially to the currentmunicipal waste management systems such as WWTP.The present WWTP were not designed to treat wastestreams containing ENPs.47�48 For example, silver ENPshave antibacterial properties49 and can adversely affect themicrobial populations in WWTP systems. Furthermore, theimpact of silver ENPs antibacterial properties on the modelbacterium Pseudomonas fluorescens showed some toxic-ity in terms of inhibiting their growth. The toxicity was

caused by intrinsic properties of the ENPs, and not bydissolution.50 In addition, another study reported that sil-ver ENPs of the 1–10 nm size range were preferentiallybound to cell membranes and were incorporated into bac-teria, whereas the larger ones were not,51 while anotherstudy showed that silver ENPs caused pitting on bacteriacell membranes leading to cell permeability, cell disrup-tion and death.52 Such properties of the ENPs are likelyto drastically reduce the efficacy of the treatment systemsparticularly those using bacteria microbial community forremoving organic matter from the wastewater.Additionally, recent preliminary studies have shown the

removal efficiencies of ENPs in municipal WWTP to rangefrom 5% (e.g., ZnO) to 90% (TiO2) for ENPs currentlyused in cosmetics.53 It is anticipated that such ENPs arelikely to pose new challenges to the present waste manage-ment systems and could fundamentally alter these treat-ment systems’ functionality.47 This is problematic giventhe fact that current data and knowledge on the environ-mental fate and behaviour of the organic (fullerenes) andinorganic (TiO2, ZnO, etc.) ENPs used in cosmetics islacking. Moreover, the un-removed ENPs may enter sur-face water environments, potentially disrupting numerousbiological ecosystems. Besides, even if the ENPs wereremoved from the WWTP systems, they are likely to re-enter the environment through the application of sludge foragricultural purposes. Results of Benn and Westerhoff54

have shown this is possible as silver ENPs were releasedfrom socks during washing.

3.3. Environmental Risk Assessment ofCosmetics ENPs

Present scientific literature has limited published data onthe actual nanowastes from any given form or type ofnanoproducts and those from cosmetics are not an excep-tion. To elucidate the extent of the cosmetics industry’scontribution to the entire global nanowastes generation andinevitable dispersion in the environment, the quantificationof such streams and/or level of risk they pose to the envi-ronment is critical for their long-term responsible man-agement. The lack of data or limited scientific literatureon nanowastes management for all types of nanoproductsand cosmetics in particular is due to lack of studies inthis domain. In addition, commercial and business interestsas well as severe market competition in the nanotechnol-ogy has contributed to limited publications on quantitiesof ENPs used in any specific industry sector, let alone thequantities of waste streams containing nanoscale materialsat production, use and disposal.To quantify risks of nanowastes from cosmetics, first,

the quantities of each type of ENPs used in the prod-ucts is necessary. Such data would provide an indi-cation of the possible quantities likely to be releasedthrough nanowastes into the environment. Second, the


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Production

Cosmetics

Application

Other NMs applications

Untreated WW

WWTP

Sewage sludge

Treated WW

Solid waste

Groundwater

Effluent

Other soils

Agriculturalsoils

LeachateSolid waste landfills

Oceans

Sediment

NaturalFreshwaters

Sediment

Leachate

System boundary NMs flow in cosmetics

Environmental compartmentsNMs flow in cosmetics

Aquatic environment

WWTP: wastewater treatment plant

WW: wastewater

Terrestrial environment

Fig. 6. Exposure pathways of ENPs from cosmetics based on South African waste management scenarios.

exposure potential of ENPs should be known in respectto bioaccumulation, biopersistence and biomagnification.And finally, extensive ecotoxicological data for ENPsused in cosmetics in different environmental organisms isrequired in order to evaluate the particles’ ecological haz-ards at different trophic levels. However, none of thesedata requirements are comprehensively accessible in theliterature.Although no exact quantities of ENPs used in nanoprod-

ucts in general or in cosmetics in particular are available,alternative sources of data suggest increasing trends in thenumber of nanoproducts, patents, nanoproducts commer-cialization, production of ENPs, and nanotechnology mar-ket in monetary terms. This will eventually lead to risingvolumes of nanowastes at different phases of the materialslife-cycle. A few examples of the alternative data are sum-marized to support our proposition on increasing volumesof nanowastes from different industrial sectors includingcosmetics.Several reports indicate that nanotechnology industry

has reached tens of billions of dollars in commerce andindustry. For example, nanotechnology-based products andapplications were estimated to be exceeding $30 billion

in value in 2005.55 Similarly, Business CommunicationsCompany (BCC) predictions on specific nanoproductscomprising of fillers, cosmetics, pharmaceuticals, cata-lysts, drug carriers, energy storage and anti-friction coat-ings were worth US $10.6 billion in 2006.56 This trendis expected to continue to rise and capital venture predic-tions for the year 2014 show that the nanotechnologically-based manufactured goods will account approximately15% of the global manufacturing output with an esti-mated economic value of US $2.6 trillion.57�58 To theauthors’ knowledge, the nanotechnology economic volumeand contribution in the cosmetics is yet to be pub-lished. However, according to recent analysis of the cos-metic global industry growth trends reveal that becauseof innovations and technologies capabilities, the industryhas the potential to maintain an average global growthrate of 5%.46 It is likely that nanotechnology will beone of the technologies to contribute to achieving suchgrowth.The global production of all types of ENPs for use in

different industrial sectors was estimated to increase from1,100 tons in 2003/2004 to 58,000 tons by 202056�59 con-sisting of metal oxides, metals, carbon-based materials,


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and quantum dots. Metal oxides, which include titaniumdioxide, zinc oxide, silicon dioxide, aluminium oxide, zir-conium and iron oxide, are currently the most importantENPs commercially. In particular, quantities estimated foruse in the skincare market sectors (titanium dioxide, zincoxide, etc.) amount to 1,000–2,000 tons per annum world-wide, with the ENPs component materials prices rangingfrom $10 to $100,000 per ton.59 Schmid and Riediker60

estimated the use of ENPs in Switzerland to be 2,419tons annually by 2007. Of these statistics, the cosmeticsindustry declared the highest quantities of TiO2 and ZnOENPs for the UV-protection. These figures illustrate thatthe cosmetic industry are among the main users of ENPsto enhance product performance.Globally there has been an exponential growth in

the commercialization of nanoproducts, including cosmet-ics containing ENPs, since 2000. An online inventoryat Woodrow Wilson International Centre for Scholars61

demonstrates the rapid growth of company-declarednanoproducts from 54 in 2005 to 1015 by August 2009(see Fig. 7). Most products are classified under the healthand fitness products category (constituting 605 of the 1015products in the inventory of August 2009). It should benoted that of the total nanoproducts in the inventory cos-metics, personal care, and sunscreens constitute about 57%of the total products under the health and fitness category,and 36% of the entire number of nanoproducts registeredin the Woodrow Wilson International Centre Inventory.Again, this suggests cosmetics are among the nanoprod-ucts likely to generate large quantities of nanowastes witheventual entry into the environment.Another inventory of nanocomponents containing ENPs

developed by Nanowerk LLC showed they increased from1979 in August 2008 to 2238 in May 2009 (13.1%)62 asdepicted in Figure 8. The rapid increase in the number

54

212 230

321356

475

580 606

803

1015

0

200

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, 200

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, 200

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, 200

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, 200

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, 200

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, 200

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ber

of p

rodu

cts

Fig. 7. Commercial nanoproducts growth from year 2005 to 2009.Modified from Ref. [58].

Fig. 8. The distribution of nanocomponents based on the NanowerkLLC Inventory.59

of products in the second inventory is consistent with thedramatic commercialization of nanoproducts reported bythe Woodrow Wilson International Centre.61 An analysison the nanocomponents distribution in the Nanowerk LLCinventory shows that the dominant ENPs are those of theelements, binary compounds, and metal oxides which findwide applications in cosmetics.Therefore, given the experience with past and present

technologies, conventional wisdom suggest that the growthof nanowastes at different phases of products lifecycle arehighly likely to be linearly correlated to the increases inthe quantities of nanoproducts fabricated. To address issuesrelated to nanowastes from cosmetics, in this paper, theirrisks to the environment using qualitative and quantitativeapproaches.

3.4. Risk Assessment of ENPs

3.4.1. Qualitative Risk Assessment of ENPs

A study by Musee47 attempted to quantify nanowasterisks for nanoproducts manufactured from different indus-trial sectors including cosmetics. The model applied wasqualitative because of the limited availability of quantita-tive data concerning the toxicity and exposure potency ofENPs. The results yielded the first nanowastes classifica-tion paradigm at the disposal phase. For clarity purposes,a brief description of the methodology used is described.Hazard of the constituent ENP in a given nanoproduct wasquantified using the toxicity values reported in the sci-entific literature. Because different authors have reporteddifferent values for the same ENP (as a good example seeKahru and Dubourguier63), the highest acute toxicity wasused in the model from a precautionary principle. Afterapplying this approach, the qualitative hazard characteriza-tion of several ENPs including those used in cosmetics issummarized in Table I. Illustrative cases of reported data


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Table I. Qualitative quantification of toxicity levels of different ENPsbased on available ecotoxicity data by August 2008.

NMs type Examples Hazard (toxicity)a

Carbon based Fullerenes HighSingled-walled carbon High

nanotubes (SWCNT)Multi-walled carbon High

nanotubes (MWCNT)

Metal oxides Zinc oxide (ZnO) MediumTitanium oxide (TiO2) LowAluminium oxide (Al2O3) MediumYttrium iron oxide (Y3Fe5O12) LowSilicon dioxide (SiO2) LowIron oxide (Fe2O3) Medium

Metals Silver (Ag) MediumGold (Au) HighSilica (Si) Low

Quantum dots Cadmium-selenide (CdSe) HighCadmium telluride (CdTe) High

Others Silicon nanowires LowNanoclay particles LowDendrimers Medium

aMeasure of ecotoxicity to different test species. The qualitative classification ofthe aquatic toxicity is based on Globally Harmonized System65�66 expressed infive classes namely; extremely toxic (<0�1 mg/l); very toxic (0.1–1 mg/l); toxic(1–10 mg/l); harmful (10–100 mg/l); and none toxic (>100 mg/l) which werereduced into the three classes (high, medium and low).Source: Reprinted with permission from [47], N. Musee, Nanotechnology riskassessment from a waste management perspective: Are the current tools adequate?Hum. Exp. Toxicol. (2011) (accepted). © 2011, SAGE Publications.

on the ENPs’ toxicity in different ecological endpointsused in cosmetics can be found in Refs. [63] and [64].The second parameter essential for quantifying the risk

of a contaminant is the exposure potency. In the environ-mental context the exposure potency is a function of sev-eral interlinked and complex factors like biopersistence,bioaccumulation, solubility, biodegradability, hydrolysis,and photolysis. However, unlike the macroscale chemi-cals of the same materials used in fabricating ENPs, thedata for the ENPs is lacking. In a study by Musee,47 theexposure potential of ENPs to ecological organisms wasestimated based on the particles’ loci in the nanoproductsbased on earlier formalism by Hansen and co-workers.67�68

As a result, the exposure potential for a given ENPs wasclassified into five categories as shown in Table II. Thepossible release of ENPs from a nanoproduct depends onhow firmly or loosely they are embedded in a given matrix.For example, ENPs incorporated in a liquid matrix aremore likely to be easily released compared to those thatare firmly bound in a solid matrix, and hence increasetheir exposure to different organisms in the environment.An illustration of this aspect is pictorially presented inFigure 9.Next step was to characterize the potential risk of ENPs

in a given product. An example of risk characteriza-tion for several products is presented in Table III includ-ing their assignment in nanowaste classes. Five classes

of nanowastes were proposed, and the most profoundfinding was that the same nanoproduct, e.g., a personalcare product or sunscreen, may range from Class-I type(most benign) to Class-V type (most hazardous) nanowastestream during the disposal phase (see Table III). Generally,for macroscale chemicals the risk profile is non-variantbecause its toxicity is a function of its structure, and there-fore, the resulting waste streams can be grouped in oneclass irrespective of the product type. However, due tothe great variance of hazards of different ENPs used inmanufacturing the same nanoproduct—due to their indi-vidual diverse physicochemical properties—the resultingnanowastes exhibit different risk profiles.For instance, sunscreens containing different ENPs (e.g.,

ZnO, TiO2, Ag, etc., see Table III) exhibit a wide vari-ance of profiles at the disposal phase. In particular, sun-screen nanowastes containing ENPs of TiO2 are likely tobe a Class I-type nanowaste stream. In contrast, if the con-stituent ENPs are ZnO, the resulting waste streams arelikely to be Class II- or Class III-type nanowastes. Thefindings suggest that the same nanoproduct but containingdifferent ENPs (e.g., cosmetics, paints, etc.) may lead todifferent classes of nanowaste streams with highly variablerisk profiles as shown in Table III, and as such, this wouldrequire different management approaches as prescribedfor different nanowaste classes as presented in Table II.A brief description of different nanowastes classes is pro-vided in Appendix A for interested readers.Therefore, we argue that due to the diversity of

nanowaste streams of the same product this situationis likely to pose new challenges on developing legisla-tions that govern waste streams containing ENPs at thedisposal phase, and with respect to standardizing wastemanagement technologies and/or approaches of handlingthem. Such diversity of potential waste streams fromcosmetics points for an urgent need for dedicated andfocussed research to understand and develop mitigationapproaches of dealing with waste streams generated dur-ing application and disposal phases. No scientific stud-ies have reported this despite increases in the use ofENPs to enhance the performance of cosmetics. Details ofapproach and methodology in data analysis are presentedelsewhere47�67�68 for interested readers.While the qualitative classification of nanowastes by

Musee47 was specifically for cosmetics it provides usefulinsights on how to approach environmental issues arisingfrom the introduction of nanotechnologically-based prod-ucts. The approach is relevant to cosmetics as illustrated inthis paper. Secondly, the qualitative approach has providedbasis for proposing and developing new classification for-malism for waste streams generated from nanotechnology-related manufacturing activities and end of lifespan wastestreams. The classification of nanowastes in different cat-egories makes it possible to isolate and focus on streamsthat are more likely to cause adverse environmental effects


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Table II. Classification of nanowaste streams as a function of constituent ENPs toxicity and their loci in the nanoproducts.

Nanowaste classes Description Possible WM protocol requirements Examples of waste streams

Class I ENPT: non-toxic; Loci: free,surface, or bulka

No special or cautionary measures required inhandling this class of waste stream. CurrentWM systems may be appropriate—though noscientific studies have been reported to verifythis observation.

Waste streams from the displaybackplane in television screens,solar panels, memory chips,polishing agents.

Class II ENPT: Harmful or toxic, Loci:surface or bulkb

Caution is essential/necessary. Need to check theplausibility of exposure levels case-by-casewaste streams to diverse ecological systems todetermine the level of precautionary measuresrequired.

Display backplane, memory chips,polishing agents, solar panels,paints and coatings

Class III ENPT: Toxic to very toxic; Loci:surface or bulkb

Nanowastes likely to be hazardous and caution isessential at various phases of WM. If highlytoxic NMs present treat the entire waste streamas hazardous.

Food packaging, food additives,wastewater containing personalcare products, polishing agents,pesticides

Class IV ENPT: Toxic to very toxic; Loci:surface or freec

Nanowastes are highly hazardous and treatmenttechnologies for hazardous waste streams shouldbe applied. However, the success of suchtechnologies is yet to be tested and published inscientific journals.

Paints and coatings, personal careproducts, pesticides, etc.

Class V ENPT: Very toxic to extremelytoxic; Loci: surface or freec

Nanowastes are extremely hazardous, requiresefficient treatment techniques before disposal.Should only be disposed in specially designedand designated waste disposal sites.

Pesticides, sunscreen lotions andfood and beverages containingfullerenes in colloidal suspensions

ENPT: ENP toxicity; WM: waste management; aexposure ranges from low to high; b low to medium exposure; csolid bound or solid-suspended hence medium to highexposure. Examples provided are based on the available data, and quantitative studies are essential to verify and enhance the transparency and credibility of the proposedclassification formalism.Source: Reprinted with permission from [47], N. Musee, Nanotechnology risk assessment from a waste management perspective: Are the current tools adequate? Hum. Exp.Toxicol. (2011) (accepted). © 2011, SAGE Publications.

within short- to long-term timeframes. From the qual-itative model approach, the cosmetic ENPs-containingnanowastes of concern contain Ag and ZnO ENPs.However, the study had several limitations as one can

only manage what is measurable. For instance, lack ofquantitative data limited the extent the model resultscan be validated and support rigorous comparison of

Bulk-based NMs (one ormultiphase)

EEPP:: VVeerryy llooww ttoo llooww

Structured surface, filmor structured

EEPP:: VVeerryy llooww ttoo mmeeddiiuumm

NMs suspended in liquids

EEPP:: HHiigghhllyy lliikkeellyy

NMs suspended in solids

EEPP:: MMeeddiiuumm ttoo vveerryy hhiigghh

Airborne/free ENPs

EEPP:: HHiigghhllyy lliikkeellyy

Surface bound

EEPP:: LLooww ttoo hhiigghh

Fig. 9. The categorization framework of ENPs exposure potency as a function of their location in a given product matrix. EP: exposure potential.Modified from Refs. [67] and [68].

environmental risks of the same nanoproduct but con-taining different ENPs. This shortcoming is addressedin the next section where a specific case study oncosmetics is described. Secondly, the proposed for-malism could not allow incorporation of risk factorsnecessary for quantifying environmental risks due tochemicals.


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Table III. Risk profiles of nanoproducts and/or applications containing ENPs at the disposal phase.

Application NMs Hazard Exposure potency Risk at disposal Potential nanowaste class

Personal care pro. Ag Medium High Medium Class II/Class IIIFullerenes High High High Class IV/Class VFe2O3 Medium High Medium Class II/Class IIITiO2 Low High Low Class I

Food/beverages TiO2 Low Medium Low Class IZnO Medium Medium Medium Class II/Class III

Fullerenes High Medium High Class IV/Class VDendrimers Medium Medium Medium Class II/Class III

Sunscreen lotions ZnO Medium High Medium Class II/Class IIITiO2 Low High Low Class I

Fullerenes High High High Class IV/Class VDendrimers Medium High Medium Class II/Class III

Pesticides Fullerenes High High High Class IV/Class VFe2O3 Medium High Medium Class II/Class III

Paints/coatings TiO2 Low Medium Low Class ISiO2 Low Medium Low Class ICdSe High Medium Medium Class II/Class III

Food packaging Ag Medium High Medium Class II/Class IIINanoclays Low High Low Class I

TiO2 Low High Low Class I

Polishing agents TiO2 Low High Low Class IZnO Medium High Medium Class II/Class III

Notes: Class I has lowest risk profile, Classes II and III exhibits moderate (medium) risk levels, and Classes IV and V have the highest degree of risk.Source: Reprinted with permission from [47], N. Musee, Nanotechnology risk assessment from a waste management perspective: Are the current tools adequate? Hum. Exp.Toxicol. (2011) (accepted). © 2011, SAGE Publications.

3.4.2. Quantitative Risk Assessment of ENPs

Recent studies have reported findings on the environmentalrisk assessment of ENPs from different types of nanoprod-ucts. The results were calculated using quantitative mod-els to estimate the predicted environmental concentrations(PEC) at country69 or continental wide-scales.70�71 Forexample, Muller and Nowack69 calculated the PEC basedon a probabilistic material flow analysis for three typesof ENPs: Ag, TiO2 and carbon nanotubes (CNT) to esti-mate their environmental impacts in air, water and soil.The PEC of the three nanoparticles showed great vari-ance in different environmental compartments, caused bydifferences in lifecycles of the nanoproducts. The studyfindings showed that TiO2 posed a higher risk to waterorganisms than Ag and CNT, and the results are summa-rized in Tables IV(a and b). The calculations indicate thatcurrently CNT pose little to no risk to air and water organ-isms probably because of the low quantities used in prod-ucts, and the materials are very expensive per unit weight.The predicted results were an aggregated value owing tothe contribution of different nanoproducts such as textiles,cosmetics, sprays, metal products, etc.Gottschalk et al.70 presented findings on the potential

environmental risks of five different ENPs, namely Ag,TiO2, CNT, ZnO and fullerenes for the U.S., Europe andSwitzerland using 2008 as the base year. The results indi-cated that risks to aquatic organisms may come from Ag,TiO2, and ZnO in sewage treatment systems for all consid-ered regions, and for Ag in surface waters (see summarised

findings in Table V). Among the ENPs considered inthe study, TiO2 showed the highest concentrations inall regions because of its high volume use in differentnanoproducts. In contrast, from the qualitative model pre-sented in Section 3.4.1, TiO2 ENPs appeared to gener-ate waste steams of minimal risks as their toxicity wasamong the lowest for the particles considered. Results forother environmental compartments for which the ecotox-icological data were available indicated no risks to theorganisms.The PEC results reported in Refs. [69] and [70] assumed

that the ENPs were homogenously mixed in all environ-mental compartments on a country or continental wide-scale. This is unlikely given that some regions have higheruses of a given type of nanoproducts, a closer proxim-ity to sewage wastewater, or a higher population densitythan other regions and as a result concentrations of ENPswill be much higher. Therefore, a study was conductedto predict the risks of ENPs in cosmetics for a local-ized area. The Johannesburg Metropolitan City WWTP inSouth Africa was used as a case study.72 The predictivequantitative model for ENPs risks in a localized regionsought to reduce the uncertainties in dealing with countryor continental spatial scales. In addition, city environmentsare expected to experience higher concentrations of ENPsparticularly from cosmetics due to increased usage per unitpopulation density.Therefore, results of Musee and Nota72 derived using a

quantitative model are summarized to illustrate the poten-tial environmental impacts of Ag and TiO2 ENPs from


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Table IV(a). PEC of nano-Ag, nano-TiO2 and carbon nanotubes (CNT) in air, water and soil.a

Nano-Ag Nano-TiO2 CNT

Unit RE HE RE HE RE HE

Air �g/m3 1�7×10−3 4�4×10−3 1�5×10−3 4�2×10−2 1�5×10−3 2�3×10−3

Water �g/l 0.03 0.08 0.7 16 0.0005 0.0008Soil �g/kg 0.02 0.1 0.4 4.8 0.01 0.02

aRE: realistic scenario; HE high emission scenario.Source. Reprinted with permission from [69], N. C. Mueller and B. Nowack, Exposure modelling of engineered nanoparticles in the environment. Environ. Sci. Technol.42, 4447 (2008). © 2008, American Chemical Society.

Table IV(b). Modelled risk quotients (PEC/PNEC) for water, soil and air.a

Nano-Ag Nano-TiO2 CNT

RE HE RE HE RE HE

Air Nd Nd 0.0015 0.004 1�5×10−5 2�3×10−5

Water 0.0008 0.002 >0�7 >16 0.005 0.008Soil Nd Nd Nd Nd Nd Nd

and: not determined due to lack of ecotoxicological data.Source. Reprinted with permission from [69], N. C. Mueller and B. Nowack, Exposure modelling of engineered nanoparticles in the environment. Environ. Sci. Technol.42, 4447 (2008). © 2008, American Chemical Society.

cosmetics to aquatic organisms. The quantitative modelwas applied to investigate whether the qualitative modelresults discussed in Section 3.4.1 can be validated if fac-tors such as the quantities of ENPs are considered in therisk assessment process. Secondly, the results reported onPEC of ENPs69–71 are based on the developed countries.

Table V. Risk quotients (PEC/PNEC) for all the ENPs and regions.

Compartment Europe U.S. Switzerland

Nano-TiO2

Surface water 0�015 0�002 0�02STP effluent 3�5 1�8 4�3Air <0�0005 <0�0005 <0�0005Soil 0�004 0�002 0�001Sludge treated soil 0�3 0�14

Nano-ZnOSurface water 0�25 0�02 0�32STP effluent 10�8 7�7 11

Nano-AgSurface water 1�1 0�17 1�03STP effluent 61�1 30�1 55�6Air <0�0005 <0�0005 <0�0005

CNTSurface water <0�0005 <0�0005 <0�0005STP effluent <0�0005 <0�0005 <0�0005Sediment <0�0005 <0�0005 <0�0005Air <0�0005 <0�0005 <0�0005Soil <0�0005 <0�0005 <0�0005Sludge treated soil <0�0005 <0�0005

FullerenesSurface water <0�0005 <0�0005 <0�0005STP effluent 0�026 0�023 0�019Soil <0�0005 <0�0005 <0�0005Sludge treated soil <0�0005 <0�0005

Source. Reprinted with permission from [70], F. Gottschalk et al., Modeled envi-ronmental concentrations of engineered nanomaterials (TiO2, ZnO, Ag, CNT,Fullerenes) for different regions. Environ. Sci. Technol. 43, 9216 (2009). © 2009,American Chemical Society.

Thus, results of Musee and Nota72 are significant as theyconsidered the impact of ENPs in the environment in thecontext of a developing country in that the ENPs removalefficiency in WWTPs is several orders of magnitude lowerthan those of developed countries. This is in contrast tothe high removal efficiencies of ENPs used in the previousstudies.69–71

The environmental risks of ENPs used in cosmeticswere modelled under minimum, probable, and maximumrelease scenarios to account for lack of data, and to min-imize inherent data uncertainties. The quantitative modelused by Musee and Nota model72 combined the approachesproposed in Refs. [69–71] to enhance the model perfor-mance and improve results reliability. The calculated PECsvalues of Johannesburg City for Ag and TiO2 are presentedin Tables VI and VII for high and low WWTPs removalefficiencies, respectively. The computed values were basedon statistics obtained from the literature and experts, andshow how the removal efficiency of ENPs in WWTPwill determine the final quantities to reach different envi-ronmental compartments through treated effluent and thesludge. Notably, if the sludge is used for agricultural pur-poses this could result in a potential transfer of ENPs intosoils, and eventually in groundwater systems.Another important factor considered in evaluating the

risk was the dilution factor. A dilution factor refersto potential change of contaminant concentration in thewastewater due to seasonal variation (wet or dry weather),and additional run-off feed into the treatment water. Thevalues vary considerably and in Europe the default value is10 (Ref. [73]) largely due to abundance of water whereasin South Africa the value is much less as the country iswater scarce. The dilution factors are always linked to therelease scenario. Therefore, dilution factors of 1 and 3


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Table VI. Modelled PEC for the Ag and TiO2 in WTTP under high removal efficiency regime.

Variable MIN-EJHB PRO-EJHB MAX-EJHB

AgAgtotal: total silver released into WW (kg/a∗) 7�77 52�79 306�58fSTP: fraction of WW treated in WWTPs 0�80 0�70 0�60fRemoval: fraction of Ag removed in WWTPs 0�79 0�70 0�55AgSTP: silver entering into WWTPs in (kg/a) 6�22 36�95 183�95AgSTP� removed: silver removed in WWTP (Ag in sludge) (kg/a) 4�91 25�87 101�17AgSTP� removed: silver released effluents from WWTPs (kg/a) 3�93 11�08 82�78Aguntreated: silver in untreated WW (kg/a) 1�55 15�84 122�63Agwater : silver that enters into aquatic environment (kg/a) 5�58 26�92 205�41

TiO2

TiO2 total: total TiO2 released into WW (kg/a) 7�03 47�73 1289�38fSTP: fraction of WW treated in WWTPs 0�80 0�70 0�60fRemoval: fraction of TiO2 removed in WWTPs 0�80 0�65 0�60TiO2 STP: TiO2 entering into WWTPs in (kg/a) 5�62 33�41 773�63TiO2STP� removed: TiO2 removed in WWTP (Ag in sludge) (kg/a) 4�50 21�72 464�18TiO2STP�removed: TiO2released effluents from WWTPs (kg/a) 1�12 11�69 309�45TiO2�untreated: TiO2 in untreated WW (kg/a) 1�41 14�32 515�75TiO2 water : TiO2 entering into the aquatic environment (kg/a) 2�53 26�01 825�21

∗kg/a; kg/annum.

were considered as well. In Johannesburg City in certainmonths of the year the dilution factor is none, and there-fore, a dilution factor close to 1 is more realistic overthe entire year. For clarity purposes, the dilution factor inthis case was the number of times the concentrations ofENPs will be diluted after the wastewater treatment in theWWTP.The risk profiles for each ENP type (Ag and TiO2)

were determined as a ratio of the PEC to the predictedno effect concentrations (PNEC) (PEC/PNEC) based onthe European Chemicals Bureau approach.73 The PNECvalues were determined based on published ecotoxicolog-ical data in the literature for each ENP under questionwithin an aquatic environment, and incorporating a riskfactor of 1,000 as outlined in the technical guidelines for

Table VII. Modelled PEC for the Ag and TiO2 in WTTP under low removal efficiency regime.

Variable MIN-EJHB PRO-EJHB MAX-EJHB

AgAgtotal: total silver released into WW (kg/a) 7�77 52�79 306�58fSTP: fraction of WW treated in WWTPs 0�80 0�70 0�60fRemoval: fraction of Ag removed in WWTPs 0�45 0�35 0�25AgSTP: silver entering into WWTPs in (kg/a) 6�22 37�0 183�95AgSTP� removed: silver removed in WWTP (Ag in sludge) (kg/a) 2�80 12�90 46�00AgSTP� removed: silver released effluents from WWTPs (kg/a) 3�40 24�00 138�10Aguntreated: silver in untreated WW (kg/a) 1�60 15�80 122�80Agwater : silver that enters into aquatic environment (kg/a) 5�00 39�90 260�90

TiO2

TiO2 total: total TiO2 released into WW (kg/a) 7�03 47�73 1289�38fSTP: fraction of WW treated in WWTPs 0�80 0�70 0�60fRemoval: fraction of TiO2 removed in WWTPs 0�45 0�35 0�25TiO2 STP: TiO2 entering into WWTPs in (kg/a) 5�60 33�40 773�60TiO2 STP� removed: TiO2 removed in WWTP (Ag in sludge) (kg/a) 2�50 11�70 193�40TiO2 STP� removed: TiO2released effluents from WWTPs (kg/a) 3�10 21�70 580�20TiO2�untreated: TiO2 in untreated WW (kg/a) 1�40 14�30 515�80TiO2 water : TiO2 entering into the aquatic environment (kg/a) 4�50 36�00 1096�0

risk assessment of chemicals by the European ChemicalsBureau.73 The calculated results for the risk ratios of Agand TiO2 are presented in Tables VIII and IX for highand low WTTP removal efficiencies, respectively. Notably,under all the three release scenarios, the risk ratios for AgENPs were less than 1. This implies that in JohannesburgCity there is little or no risk posed by Ag ENPs fromcosmetics to aquatic organisms irrespective of the removalefficiency regime in the WTTP systems and the dilutionfactor under consideration.For TiO2 under maximum release scenarios, however,

the risk ratios were around or above 1 specifically whenthe dilution factors were 1 or 3. This implies that cosmet-ics containing TiO2 ENPs pose higher environmental risksto the aquatic organisms in Johannesburg City. As such,


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Table VIII. Modelled risk ratios for the Ag and TiO2 in WTTP under high removal efficiency regime.

Parameters MIN-EJHB PRO-EJHB MAX-EJHB

nAgConcentration in STP (�g/l) 4.8E−03a 7.68E−03b 36.28E−03a 90.58E−03b 23.268E−03a 1038.48E−03b

Dilution factor: 10 (PEC, �g/l) 0.2E−03 0.3E−03 1.8E−03 4.6E−03 15.6E−03 69.6E−03Dilution factor: 3 (PEC, �g/l) 0.6E−03 0.9 E−03 6.2E−03 15.4E−03 52E−03 231.9E−03Dilution factor: 1 (PEC, �g/l) 1.8E−03 2.8E−03 18.5E−03 46.2E−03 155.9E−03 695.7E−03RQ (D = 10) (no units) 4.44E−06 7.01E−06 4.62E−05 1.15E−04 3.90E−04 1.74E−03RQ (D = 3) (no units) 1.48E−05 2.34E−05 1.54E−04 3.85E−04 1.30E−03 5.80E−03RQ (D = 1) (no units) 4.44E−05 7.01E−05 4.62E−04 1.15E−03 3.90E−03 1.74E−02

nTiO2

Concentration in STP (�g/l) 4.4E−03 6.9E−03 32.7E−03 81.8E−03 977.2E−03 4 361.9E−03Dilution factor: 10 (PEC, �g/l) 0.2E−03 0.3E−03 1.8E−03 4.5E−03 62.5E−03 279.2E−03Dilution factor: 3 (PEC, �g/l) 0.5E−03 0.8E−03 5.9E−03 14.9E−03 208.5E−03 930.5E−03Dilution factor: 1 (PEC, �g/l) 1.6E−03 2.5E−03 17.8E−03 44.6E−03 625.4E−03 2 791.6E−03RQ (D = 10) (no units) 1.57E−04 2.48E−04 1.78E−03 4.46E−03 6.25E−02 2.79E−01RQ (D = 3) (no units) 5.24E−04 8.26E−04 5.95E−03 1.49E−02 2.08E−01 9.31E−01RQ (D = 1) (no units) 1.57E−03 2.48E−03 1.78E−02 4.46E−02 6.25E−01 2.79E+00

aValues based on computed wastewater per capita in Johannesburg for the three scenarios. bValues based on data provided by experts on wastewater per capita in Johannesburgfor the three scenarios.

waste management of ENPs in effluents should focus moreon waste streams containing TiO2 as they pose immediaterisks. On the one hand, our results are agreement with pre-vious modelling results.69–71 On the other hand, the quanti-tative results expose the weakness of qualitative approachin determining risks posed by chemicals to the environ-ment. For instance, in the qualitative model, cosmeticscontaining TiO2 had very low risk as opposed to those con-taining Ag. However, when the total quantities used pertype of ENP are factored in, a different scenario arises. Theresults suggest that to effectively quantify risk assessmentof environmental contaminants, the quantity factor has tobe considered as recently shown by several authors74–77 forwaste streams containing macroscale chemicals. This isbecause the quantity influences the eventual concentrationof the contaminant that interacts with the organisms.

Table IX. Modelled risk ratios for the Ag and TiO2 in WTTP under low removal efficiency regime.

Parameters MIN-EJHB PRO-EJHB MAX-EJHB

nAgConcentration in STP (�g/l) 4.8E−03a 7.68E−03b 36.28E−03a 90.58E−03b 23.268E−03a 1038.48E−03b

Dilution factor: 10 (PEC, �g/l) 0.3E−03 0.5E−03 2.7E−03 6.8E−03 19.8E−03 88.3E−03Dilution factor: 3 (PEC, �g/l) 1.0E−03 1.6E−03 9.1E−03 22.8E−03 65.9E−03 294.2E−03Dilution factor: 1 (PEC, �g/l) 3.1E−03 4.9E−03 27.3E−03 68.3E−03 197.7E−03 882.6E−03RQ (D = 10) (no units) 7.72E−06 1.22E−05 6.83E−05 1.71E−04 4.94E−04 2.21E−03RQ (D = 3) (no units) 2.57E−05 4.06E−05 2.28E−04 5.69E−04 1.65E−03 7.35E−03RQ (no dilution) (no units) 7.72E−05 1.22E−04 6.83E−04 1.71E−03 4.94E−03 2.21E−02

nTiO2

Concentration in STP (�g/l) 4.4E−03 6.9E−03 32.7E−03 81.8E−03 977.2E−03 4 361.9E−03Dilution factor: 10 (PEC, �g/l) 0.3E−03 0.4E−03 2.5E−03 6.2E−03 83.1E−03 370.8E−03Dilution factor: 3 (PEC, �g/l) 0.9E−03 1.5E−03 8.2E−03 20.6E−03 276.9E−03 1 235.9E−03Dilution factor: 1 (PEC, �g/l) 2.8E−03 4.4E−03 24.7E−03 61.8E−03 830.6E−03 3 707.6E−03RQ (D = 10) (no units) 2.79E−04 4.41E−04 2.47E−03 6.18E−03 8.31E−02 3.71E−01RQ (D = 3) (no units) 9.31E−04 1.47E−03 8.24E−03 2.06E−02 2.77E−01 1.24E+00RQ (D = 1) (no units) 2.79E−03 4.41E−03 2.47E−02 6.18E−02 8.31E−01 3.71E+00

aValues based on computed wastewater per capita in Johannesburg for the three scenarios. bValues based on data provided by experts on wastewater per capita in Johannesburgfor the three scenarios.

The significance of these findings is the insight they pro-vide regarding the potential risks posed by different ENPsused in fabricating the same type of nanoproducts. It isclear that different ENPs even when used for the manu-facture of the same product are likely to pose differentenvironmental threats as shown by both the quantitativeand qualitative models. Secondly, the quantitative resultsshow that TiO2 appears to present immediate threat to theenvironment due to its large global production and widespread application in cosmetics.We acknowledge that although the model provides a

road map in understanding the possible releases and poten-tial environmental risks of specific ENPs in a givennanoproduct, further investigations are crucially importantto enhance its robustness. First, the data for the produc-tion and application of a given type of ENPs to a specific


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nanoproduct needs to be improved. Currently, the acces-sible data in this sense is highly uncertain. Second, eco-toxicological data reported for ENPs in water, air or soilis very limited, and if available, its interpretability andconsistency is highly hindered by several factors. Theseinclude the experimental methodology of the essays, thedifferences in physicochemical properties of the materi-als under study, the influence of the abiotic factors, theaggregation of the particles, and the absence of experi-mental data for the actual ENPs detected in the environ-ment for specific nanoproducts due to limited metrology,etc. Third, the study results are focussed on volumes in asingle calendar year without considering the accumulativeeffects of the ENPs in the environment over a considerableperiod of time. Such investigations would provide a bet-ter understanding on the possible long-term treats of ENPsfrom cosmetics to the environment. Finally and partic-ularly applicable to developing countries, because mostof the sludge from South Africa is used for agriculturalapplications, the environment risks of ENPs into the soil,sediments, surface water and underground aquifers needsto be examined as well.In summary, our study has shown that some types of

ENPs particularly TiO2 in cosmetics are likely to pose animmediate threat to the environment in comparison to Ag.

4. CHALLENGES FOR THE FUTURE

It is beyond any doubt that the main reason for usingENPs in cosmetics is purely cosmetic, i.e., they ‘only’assist in creating a cosmetically acceptable and thereforetransparent sunscreen formulation. The smaller the ENPs,the more transparent these formulations become but at thesame time, the ENPs lose their protective characteristics(see Fig. 1). But the extensive review of recent papersinvestigating the skin penetration of NPs clearly suggeststhat the ENPs used in cosmetics (TiO2, ZnO and Ag) donot penetrate skin beyond the stratum corneum. This con-clusion is the same as one of us made already about oneyear earlier,13 but enormous scientific progress has beenmade since that allows us to explain some controversialfindings from the past. They turn out to be mainly relatedto experimental conditions and physico-chemical charac-teristics, such as:1. the origin of skin (pig and rat skin showed a higherpenetration of ENPs than human skin);2. the intactness of this skin (abrasion and sandpaperingthe skin increases skin penetration);3. the movement of this skin (flexing and massagingincreases the uptake into the stratum corneum);4. the size of the ENPs (only the smaller ones have beenfound to penetrate);5. the chemical nature of the core of the ENP (those usedin cosmetics have not (yet) been found to penetrate beyondthe stratum corneum);

6. the coating of the ENPs (anionic coatings have a loweraffinity for the stratum corneum and therefore penetrateslower into the stratum corneum than those with a neutralor cationic coating);7. the vehicle in which the ENPs are applied (hereour knowledge is too incomplete to make specificrecommendations).

Based on all the above, it is quite clear that the onlyway to study the skin penetration of ENPs from cosmeticsis to perform in vivo experiments on human skin, usingcosmetic ENPs dosed in cosmetic formulations. Despitealmost hundred papers published to date, only two studieshave been performed investigating ENPs used in cosmeticsand dosed in cosmetic formulations in vivo and both showthat these ENPs did not penetrate skin.18�37 More studieswill need to be performed to confirm these findings inde-pendently, but all evidence confers to the direction thatENPs used in sunscreen formulations under normal in-useconditions do penetrate into the uppermost layers of thestratum corneum. Until now, however, no penetration intothe deeper, living skin layers has been observed. Hence,the authors agree with the conclusions made in both thesepapers, namely that “the form of ZnO-nano studied here isunlikely to result in safety concerns”18 and that “significantpenetration (of TiO2 and ZnO ENPs) towards the under-lying keratinocytes is unlikely.”37 This, however, does notguarantee that there is no dermal penetration at all, butwhatever quantities penetrate deeper are below the lim-its of detections. Likewise, it also does not mean that noartificial situations can be created in which ENPs can pen-etrate the viable human skin layers, such as sandpaperingthe skin.Accepting the fact that ENPs do not penetrate human

skin when applied in cosmetic products (as described inSection 2), these ENPs are bound to end up in the envi-ronment (as described in Section 3). To achieve a realisticand robust risk assessment of ENPs from cosmetics, thedata used for quantitative models needs to be improved.There are numerous data gaps in the presented model thatcompromise the reliability of the results. Safe and respon-sible applications of ENPs requires that the risk profilingof each ENP be estimated using the most reliable data.Therefore, quantities used for each ENP in cosmetics needto be well documented so that the credibility of the resultsof risk assessment will be enhanced. This will allow amore accurate evaluation of the potential short- and long-term environmental impact of ENPs.Further investigations are therefore necessary that con-

sider all necessary data inputs. In addition to keeping anupdated inventory of ENPs used in cosmetics, there isa growing need for studies into their bioaccumulation,biopersistence, biomagnification, solubility, hydrolysis andphotolysis in different environmental compartments. Datais lacking and this prohibits the assessment of realisticexposure potency of ENPs in these compartments. Such


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research should be supported from the cosmetic industryto the same extent as they have been supporting skin pen-etration studies of ENPs.Why should the cosmetics invest in such research? It

is in the opinion of the authors as much as nanotechnol-ogy has surpassed industrial boundaries—in the event ofadverse environmental effects—different industrial sectorswill be equally affected because none or very few of thesesectors have data to support the view that the nanoscalematerials they use have no impact into the environment.In fact, if environmental adverse effects do occur the abil-ity for a given industrial sector to dissociate itself wouldbe virtually impossible in the absence of data. There-fore, cosmetic industry can take advantage of the infancystage of nanotechnology industry growth to generate dataconcerning specific environmental risk profiles in water(freshwater, marine, surface and underground water), soil,sediments, and air. Such data can also be used in address-ing rising concerns being voiced by consumers, regulatoryauthorities, pressure groups and governments on the poten-tial environmental risks of ENPs.Therefore, in order to convince the general public about

the lack of safety concerns relating to ENPs used in cos-metics, it would be wise for the cosmetic industry to bemuch more open towards the general public with respectto its use of nanotechnology in cosmetic products.78 Ifthe cosmetic industry is not providing details on the useof ENPs in its products and does not share with pres-sure groups like Friends of the Earth their latest scientificfindings on the skin penetration of ENPs, then it is onlylogical that the general public assumes that this industryhas something to hide. But at the same time, all scientists,both academic and industrial, need to be more careful inthe way they phrase their conclusions. The fact that somespecific ENPs can be found in the deeper viable skin layersdoes not imply that every ENP penetrates into the livingtissue of the skin. And even if carefully phrased, pressuregroups that claim to protect the public interests’ will needto accept that oversimplification of scientific findings cre-ates mistakes, a vision that the world is black and white.All parties need to become transparent in their actions andintents. The cosmetic industry is using nanotechnology inorder to be transparent. The question to be addressed nowis whether the nanotechnology industry can be transpar-ent about its use of nanotechnology in cosmetic and otherproducts and if pressure groups are crystal clear abouttheir statements on real risks towards the general pub-lic? Transparency in cosmetics needs nanotechnology, butnanotechnology in cosmetics also needs transparency � � �

APPENDIX A

For the purpose of clarity, salient characteristics of eachof the five nanowaste classes47 are summarized below.

• Class I nanowastes. Under this category the nanowasteshave very low or no toxic effects in humans and otherecological systems owing to non-toxic constituent nano-materials (NMs). In this case the exposure potency isdeemed to have no influence in the overall hazardous-ness of the nanowaste whether the NMs are bound on thesurface or inside the bulk part of the product. Examplesof such nanowastes are likely to include those generatedfrom display backplane in television screens, solar panels,or memory chips containing silicon nanowires though theexposure levels may range from low to high during thedisposal phase—if the NMs break away or leach out.• Class II nanowastes. These are nanowastes likely toexert harmful or toxic effects on humans and other organ-isms because the constituent NMs exhibits toxicity whichcan be ranked as low to high. Based on the results obtainedfrom the matrix developed to derive the classes of thenanowastes, the overall waste risk was established to bestrongly linked to the exposure potency due to nano-structures embedded on the surface or inside the bulk partof the nanoproduct. If the exposure potency is low orunlikely, such wastes may be handled as non-toxic thoughthey contain highly toxic materials. Examples includenanowastes generated after the lifespan expiry of displaybackplane and memory chips. Both nanoproducts containssingled walled carbon nanotubes (SWCNT)and accordingto the findings of Blaise et al.79 and Roberts et al.80 theseNMs are harmful or toxic to organisms (e.g., Daphniamagna or rainbow trout), and therefore, are likely to causeadverse effects if released into the environment.However, because the nanostructures in these nanoprod-

ucts are firmly bound to the products, the overall haz-ard risk to the environment may range from very low tomedium after being disposed of. Therefore, in Class IInanowastes the exposure potential strongly influences thelevel of risk for the nanowaste stream. It is therefore rec-ommended that great care be exercised in choice of dis-posal technique adopted because of the likelihood for thedegradation of the nanowastes, consequently, leading tothe release of toxic NMs into the environment.• Class III nanowastes. A nanowaste stream is classifiedas Class III type if its toxicity can be categorized as toxicto very toxic accompanied by low to medium potentialexposure during the disposal phase. For instance, currentlyzinc oxide engineered nanoparticles are being applied formanufacturing food additives. Findings of Adams et al.81

have shown that zinc oxide is very toxic to Daphniamagna. On the other hand, the exposure of the NMs infood additives is expected to be moderate during the dis-posal phase. Therefore, the resultant waste stream is likelyto have medium risk potential to the ecological systems,and should to be handled as hazardous waste.• Class IV nanowastes. Toxicity hazard of NMs in thiscategory ranges from toxic to very toxic, and the exposurepotential ranked as medium to high because the NMs in


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the nanoproduct are anticipated to be freely bound to thenanoproducts (in liquid- or solid-bound form). Consideringthe toxic nature and high expected degree of exposure, thewaste streams may result to being regarded as highly haz-ardous. Therefore, the waste requires specialized handlingand should be treated adequately either by immobilizingor neutralizing the NMs—before they are disposed of.For instance, nanowaste streams of paints and coat-

ings containing CdSe could be highly hazardous. This isbecause CdSe quantum dots are highly toxic and expectedexposure during the disposal phase is moderately high.Therefore, such waste streams should be handled withcare to avoid or minimize their long term effects into theenvironment.• Class V nanowastes. Nanowastes in this category areextremely hazardous as the constituent NMs hazard rangesfrom very toxic to extremely toxic, and the degree of expo-sure is high. Such waste streams require specialized han-dling, effective treatment, and must be disposed of in welldesigned designated disposal sites. Continuous monitoringof the sites is recommended to ensure that leachate fromthe disposal site are adequately managed. Among the mostsuitable technologies for treating such wastes includesimmobilization and neutralization processes. For illustra-tive purposes, assume that an expired pesticide needs to bedisposed of, and contains fullerenes suspended in a col-loidal solution. The waste stream is not only extremelytoxic, but also, likely to have very high exposure potentialwhen released into the environment as it in liquid form,potentially promotes easy interactions with environmentalorganisms.

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Received: 18 January 2010. Accepted: 28 April 2010.


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