Risk assessment of amorphous silicon dioxide nanoparticles in a glasscleaner formulation
Karin Michel1, Julia Scheel1, Stefan Karsten2, Norbert Stelter3, & Thorsten Wind3
1Henkel AG & Co. KGaA, Corporate Scientific Services – Toxicology, Düsseldorf, Germany, 2Henkel AG & Co. KGaA, InternationalR&D Chemistry, Laundry and Home Care, Düsseldorf, Germany and 3Henkel AG & Co. KGaA, Corporate Scientific Services –Ecology, Düsseldorf, Germany
AbstractSince nanomaterials are a heterogeneous group of substancesused in various applications, risk assessment needs to be doneon a case-by-case basis. Here the authors assess the risk (hazardand exposure) of a glass cleaner with synthetic amorphoussilicon dioxide (SAS) nanoparticles during production andconsumer use (spray application). As the colloidal material usedis similar to previously investigated SAS, the hazard profile wasconsidered to be comparable. Overall, SAS has a low toxicity.Worker exposure was analysed to be well controlled. The particlesize distribution indicated that the aerosol droplets were in a sizerange not expected to reach the alveoli. Predictive modellingwas used to approximate external exposure concentrations.Consumer and environmental exposure were estimatedconservatively and were not of concern. It was concluded basedon the available weight-of-evidence that the production andapplication of the glass cleaner is safe for humans and theenvironment under intended use conditions.
With growing expectations towards the benefits of nanotech-nology, an increasing concern with respect to potentialhealth and environmental risks, in particular those of nano-materials, can be observed in the general public and thescientific community (Borm et al. 2006b; Kreyling et al. 2006;Krug & Wick 2011; Nel et al. 2006; Royal Academy ofEngineering 2004). Various suggestions have been put for-ward to define the term “nanomaterial” (EU 2011; Interna-tional Organization for Standardization 2008; SCENIHR2010) usually addressing dimensions below 100 nm.
General concerns are expressed that due to the small size ofnanoparticles and their corresponding large specific surfacearea a greater biological reactivity may lead to negative health
implications. Specific concerns have been raised that nano-particles with a fibrous shape and a high biopersistence mayhave asbestos-like hazardous properties due to their dimen-sions (Donaldson et al. 2010; Polandet al. 2008).Moreover, therole and importance of a potential translocation of nanopar-ticles fromtheprimary siteofentry tosecondaryorgansand theresultingeffects causedbyenhancedbiodistribution is amatterof debate (Borm et al. 2006a; Kreyling et al. 2006; Oberdörster2009). Acknowledging theheterogeneity of this class ofmateri-als, the European Commission’s Scientific Committee onEmerging and Newly Identified Health Risks (SCENIHR) sug-gested that the risk assessment of nanoparticles should becarried out on a case-by-casebasis byusing a stagedapproach,including specific hazard identification and exposure analysis(SCENIHR 2007).
To the authors’ knowledge, only few case studies havebeen published demonstrating the risk assessment for theuse of nanomaterials in specific products or applications(e.g. Dekkers et al. 2011; DuPont 2007). Here the authorsprovide a specific risk assessment for colloidal syntheticamorphous silicon dioxide (SAS) in a glass cleaner formu-lation intended for consumer use in Europe, which wasconducted for different life cycle steps with a special focuson the use by consumers and the potential effects onhumans and the environment.
The variety of silicon dioxide specifications has beendescribed elsewhere (ECETOC 2006). Amorphous silicondioxide also exists in nature, for example as diatomite,and differs in its morphology from the crystalline form. Itis assumed that the major load of silicon dioxide in naturalsurface water originates from geogenic and weathering pro-cesses (Miretzky et al. 2001) and is subject to significantseasonal variations.
SAS has been in human use for decades, for example as afood additive (E 551) without any limitation for a certainparticle size (EU 2008a), but also as filler in the rubberindustry, as auxiliary material in paper and textile industryor as anticaking agent for various drug preparations.
Description of the raw material: colloidal SASThe raw material used in the formulation of the glass cleaneris a colloidal dispersion of pure discrete spherical uncoatedsilicon dioxide particles (30% (w/w), CAS 7631-86-9, EINECS231-545-4) in water. According to the supplier, the disper-sion is electrostatically stabilised by small amounts ofsodium hydroxide (0.55% as Na2O titrated value) (EKAChemicals AB 2003). Residues of individual trace metalsare below 40 ppm, except for Al (140 ppm). The materialcharacterisation is summarised in Table I. Shape and particlesize of the colloidal SAS were investigated by transmissionelectron microscopy (TEM) with a Philips CM 12 microscope(Philips, Eindhoven, The Netherlands). The rawmaterial wassprayed on a copper grid coated with a Formvar� film (spraypreparation). The micrographs were taken with 120 kV in abright field mode. In addition, particle size distribution wasinvestigated by dynamic light scattering (DLS) using a Zeta-sizer Nano ZS (Malvern Instrument Ltd., Malvern, UK). Thedistribution is expressed in vol%. After applying the rawmaterial on a glass slide, particles were investigated byatomic force microscopy (AFM) with a Nanoscope III micro-scope (Vecco Digital Instruments, Inc. Santa Barbara, CA,USA). Measurements were made in none contact tappingmode (amplitude).
Glass cleaner formulation and packagingIt has previously been shown that application of particledispersions on hard ceramic surfaces can lead to self-organisation of the nanoparticles resulting in enhanced drain-age, increased drying speed and reduced re-soiling comparedwith the conventional technology (Dreja et al. 2004). Theseeffects were elaborated for the development of a glass clean-ing product for consumer use. Colloidal SAS is added to theformulation in order to modify the glass surface. Duringdrying the hydroxyl groups of the colloidal SAS can reactby forming siloxane bonds linking the particles together or tothe surface, thus leading to enhanced hydrophilicity. Withthis modification the water film drains fast and homo-geneously resulting in improved cleanliness.
Suitable surfactants, solvents and other cleaning compo-nents are also contained but cannot be fully disclosed due tointellectual property rights. General information can beobtained under the US Patent US7745383 (Dreja et al. 2010)or the German Patent Application DE102004019022A1(Dreja et al. 2005). The colloidal silicon dioxide is appliedwith0.3% (w/w) in the formulation resulting in a concentrationof 0.09% (w/w) of silicon dioxide. The product is packed andmarketed in a trigger bottle. One spray shot has a volume ofabout 2 ml, which corresponds to roughly 2 g of the product.
Risk assessment strategyFigure 1 provides an overview of the methodologicalapproach and the tools applied in the present assessment.A central element is the physico-chemical characterisation ofthe substance. The assessment of its toxicological and eco-logical properties is based on various data sources including acomprehensive literature review and read-across analyses.Exposure assessment includes the production process andthe application by consumers for each the human and envi-ronmental assessment. The elements are described in moredetail in the following chapters (Literature search and review,Determination of the particle size distribution of the glasscleaner aerosol, Modelling of consumer exposure using thesoftware ConsExpo 4.1,Modelling of environmental exposureusing the software EUSES 2.1 and the result section).
Literature search and reviewIn addition to information provided by the raw materialsupplier, a literature search on the toxicological and eco-logical properties of SAS was performed in various data-bases and internet sources (PubMed, Medline, IUCLID) inFebruary 2011 (Figure 2). Articles were selected by screen-ing the titles and/or abstracts for relevant toxicologicaland ecological information on SAS. Additional referenceswere identified through cross-references and searches onspecific topics, resulting in 18 most relevant articles includ-ing some comprehensive reviews that were selected fordetailed review based on well-documented materials andprocedures.
Determination of the particle size distributionof the glass cleaner aerosolParticle size distribution of the aerosol droplets was mea-sured. For this purpose, six trigger bottles of the glass cleanerwere examined in quintuplicate, three with open sieve at thetrigger (resulting in a spray) and three with closed sieve(resulting in a foam) (see results, Table II, “Formulation 1”).An independent repeat was conducted with another sixbottles of another batch (see results, Table II “Formulation2”). The studies were conducted in compliance with thePrinciples of Good Laboratory Practice (EU 2004).
Equipment and set-upThe particle size analyser Spraytec RTS 5006 with worksta-tion (Malvern Instruments GmbH, Germany) was usedwith the following settings: laser wavelength: 670 nm; focallength: 100 nm; distance of dispersion unit from opticalpath/detector: 60 nm/150 nm;mode: flashmode; acquisition
Table I. Characterisation and physico-chemical properties of the rawmaterial: colloidal SAS.
*Values relate to the monomeric structure; DLS, dynamic light scattering; SAS,synthetic amorphous silicon dioxide; TEM, transmission electron microscopy.
Risk assessment of SiO2 in a cleaner
rate: 1 Hz (measurement per second), duty cycle: 0% (singlescan); data acquisition period: 5000 ms; trigger: transmission95%. According to specifications, the instrument can detectparticles down to a size of 500 nm.
MeasurementBackground measurements were performed and fulfilledthe specified requirements (transmission >1500 and signalintensity for each detector ring <50). Samples were manuallysprayed into the laser stream for 5 s in a 90� angle (approx.20 strokes). The particle size distribution was recorded.Results are reported as average particle diameters at givenpercentages (10%, 50% and 90%) of the cumulative volumeand as cumulative volume at particle diameters of 3.97 and10.44 mm
Modelling of consumer exposure usingthe software ConsExpo 4.1Consumer exposure was modelled with the softwareConsExpo 4.1. (2008, Rijksinstituut voor Volksgezondheiden Milieu). Where applicable, default parameter valueswere used (selection of glass cleaner from the defaultsdatabase: product databases: cleaning and washing; prod-uct categories: miscellaneous; scenarios: application:spraying). In the following cases parameters were adapted:weight fraction compound: 0.1%; application frequency:3/day (corresponds to cleaning of windows in three rooms),spraying away from exposed person; spray duration 30 s(sum per room); exposure duration in one room: 10 min;room size 58 m3; mass generation rate: 2 g/s (1 stroke persecond); ventilation rate (as worst-case): 0.5/h; particle
distribution median: 100 mm (default value), particledistribution coefficient of variation 0.6 fraction (defaultvalue); inhalation cut-off diameter: 100 mm (to be compa-rable with the workplace exposure limit of SAS whichrefers to total inhalable dust); uptake fraction 1 (= 100%of the substance in the air will be inhaled, worst-case assumption); inhalation rate: 32.9 m3/day (defaultbased on light exercise of a person with a body weight of60 kg). The result is given in the output section of thesoftware as inhalation point estimate. To account for acci-dental spraying towards a person, one parameter wasmodified (tick box at “spraying towards exposed person”,cloud volume 0.125 m3) and the air concentrationcalculated separately.
Modelling of environmental exposure usingthe software EUSES 2.1Environmental exposure is modelled by the EuropeanUnion System for the Evaluation of Substances (EUSES),a computer tool (v. 2.1). It is based on the Europeantechnical guidance documents for risk assessment ofnew and existing substances and biocides (EU 2008b). Dueto the variety of applications the emissions were assumed toenter wide dispersive into the environment and not in formofa few single local point sources. Explanations for tonnagesused will be given in Chapter 34.3 (Exposure assessment forthe consumer use of the glass cleaner).
Results: risk assessment
The risk of colloidal SAS in a glass cleaner intended forconsumer use is assessed. Taking the identified hazardous
� Analysis of the production process
� Toxicological information from raw material suppliers
� Comprehensive literature search
� Toxicological information from raw material suppliers
� Comprehensive literature search
� Grouping/read-across assumptions for closely related SAS specifications
� History of useCharacterisation of physico-
chemical properties
Human hazard assessment
Human exposure assessment
Environmental hazard assessment
Environmental exposure assessment
ProductionConsumer use
� Analysis of the production process
� Analysis of the application conditions and spray particle size
� Exposure modeling with ConsExpo 4.1
� TEM
� AFM
� DLS
ProductionConsumer use
� Analysis of naturaloccurrence and general consumption
� Exposure modeling with EUSES 2.1
� Supplier information
� Literature data
� Analysis of spray particle size (product)
Figure 1. Overview on themethodological approach and building blocks of the risk assessment. Methodsmentioned in detail indicate experimentalanalyses performed in this case study.
K. Michel et al.
properties and the exposure information into account andapplyingaweight-of-evidenceapproach,afinalconclusion fortheproductionanduseof the cleaner is drawn.Theevaluationis also put into perspective with the widespread occurrenceand use of silicon dioxides.
Characterisation and physico-chemical properties of theraw material and comparison with other SAS typesCharacterisationParticle size, size distribution, shape and aggregation stateof the colloidal SAS were investigated by TEM (Figure 3) andDLS (Figure 4). Particles occur as individual objects ofspherical shape, with many particles being aggregated oragglomerated. The stated particle size of 9 nm could beconfirmed with the detected size ranging from about 10 to20 nm as analysed by TEM and 4 to 40 nm by DLS.
In order to investigate the appearance of the colloidal SASon the glass surface, the surface topography was measuredby AFM. A rough structure with spherical elevations could beobserved for the surface treated with the colloidal SAS. Theelevations comprise a size range of about 60–200 nm(Figure 5). From the distorted edges it is concluded thatthe primary particles of colloidal SAS agglomerated on theglass surface which resulted in larger assemblies.
Physico-chemical properties and comparisonwith other SAS typesPhysico-chemical properties of SAS are also specifiedin Table I. Specific properties of the colloidal SAS containedin the raw material were compared with properties of otherSAS types which have been investigated and assessed before.Although different specifications of commercial SAS existdue to variations in the production processes, similarities incomposition and in physico-chemical properties have pre-viously justified read-across assumptions in a categoryapproach for hazard characterisation (CIR 2009; OECD2004; ECETOC 2006; Fruijtier-Pölloth 2012). For the purposeof the present risk assessment particle size, surface proper-ties and solubility of SAS are described in more detail.
Particle size and surface properties. Commercial SAS usuallyhave particle sizes between 1 and 350 mm referring to aggre-gates and agglomerates with primary particle sizes in theorder of a few nanometres (AGS 2006; OECD 2004). Theprimary particles of SAS have not only recently been deter-mined to be at the nanoscale but have been in that sizealready in the past. Although primary particles usually aggre-gate and agglomerate, it is very likely that single particles havebeen present in the studies conducted for the various types of
(((Silica) OR silicon dioxide) OR SiO2)
AND
Amorphous
NP = ((nanoparticle) OR nanoparticles)
24NS = nanostructured
78NT = nanotechnology nanomaterial
164NM = ((nanomaterial) OR nanomaterials)
143
AND
0035Solubility61
0032((toxicokinetics) OR biodistribution)22
0000(free AND radical AND formation)4
0025Inflammation31
0045((reactive AND oxygen AND species) OR ROS)16
1022(oxidative AND stress)4
0011(((carcinogenicity) OR carcinogenic) OR carcinogen)40
0032(((mutagenicity) OR mutagenic) OR mutagen)5
0044((genotoxicity) OR genotoxic)9
101617((cytotoxicity) OR cytotoxic) 47
112425((toxicity) OR toxic)118
NSNTNMNP
AND
AND
64600
1213
Figure 2. Literature search for toxicological information: the search terms and links between search terms are given as well as the number of hits.
Risk assessment of SiO2 in a cleaner
SAS though the specifications mostly have not been reportedin such detail. Colloidal SAS consists of primary particlesand aggregates thereof in the liquid system which typicallyagglomerate irreversibly on drying (ECETOC 2006). This is inaccordance with the investigations applying AFM.
SAS are hydrophilic if not surface-modified. This is alsothe case for the colloidal SAS in the current application.Silanol groups on the surface are neutralised with causticsoda for reasons of stabilisation resulting in a relatively inert
structure. Regarding the specific surface area, the agglom-erated powders of pyrogenic or precipitated SAS, for whichmost of the toxicological data have been generated, have aspecific surface area measured by BET (Brunauer, Emmettand Teller) method comparable with a dried colloidal SASsample (ECETOC 2006). For the colloidal SAS used in theglass cleaner, it seems therefore unlikely that hazardouseffects specifically related with the particle surface differfrom the well-investigated hydrophilic SAS.
Solubility. Dissolution of solid silicon dioxide to monosilicicacid follows the overall equation: SiO2 + 2 H2O a Si(OH)4.The solubility of amorphous and crystalline silicon dioxidehas been investigated and is reflected in the report on SASpublished by ECETOC (2006). Whereas quartz exhibited alow solubility of 5 mg/l, dissolved SAS had a saturationconcentration of 2.0 mmol/l (120 mg/l) at 25�C (ECETOC2006; Roelofs & Vogelsberger 2004). Early experiments onsolubility of different SAS forms revealed a steady stateequilibrium solubility of SAS powder (specific surface240 m2/g) reached within 20 days in distilled water. Thesolubility reached 140 mg/l free monomeric silicon dioxidein solution determined by spectrophotometry of an at least3 g/l nominal powder concentration (Alexander et al. 1954).The authors also investigated solubility of alkaline and acidcolloidal SAS and silicon dioxide gels. The occurrence ofmonomeric silicon dioxide in solution was found to slightlyincrease with increasing pH. Hence, solubility increasedfrom acid to alkaline environment from 100 to 150 mg/land was thus well comparable with the solubility of siliciumdioxide powder. In more recent experiments, pyrogenic andprecipitated types of SAS (surface area 192–376 m2/g (BET),size of primary particles 7–14 nm) have been dissolved underbiomimetic conditions in a buffer system and in simulatedextracellular lung fluid at 37�C (pH 7.4, suspension of 1 g/l).Analytical measurements were done using the molybdic acidmethod referenced in the publication. The experimental andtheoretical investigations demonstrated that particles with
Table II. Aerosol droplet size distribution of the glass cleaner.
Test item no.
Dv1
(10%)(mm)
Dv1
(50%)(mm)
Dv1
(90%)(mm)
Cv2
(%) at3.97 mm
Cv2 (%)at
10.44 mmFormulation 1: spray/open sieve
1 30.933 82.06 181.96 0.00 0.82
2 39.69 113.34 201.98 0.00 0.46
3 32.28 90.55 188.35 0.00 0.68
Mean 34 95 191 0.0 0.7Formulation 1: foam/closed sieve
4 56.03 126.61 202.75 0.00 0.19
5 55.30 128.98 206.88 0.00 0.21
6 54.23 125.83 205.62 0.00 0.22
Mean 55 127 205 0.0 0.2Formulation 2: spray/ open sieve
1 29.433 83.96 185.08 0.00 0.84
2 29.57 80.47 186.01 0.00 0.88
3 23.99 60.69 161.88 0.00 1.52
Mean 28 75 178 0.0 1.1Formulation 2: foam/ closed sieve
4 52.87 126.11 205.25 0.00 0.22
5 57.33 128.91 207.12 0.00 0.19
6 51.67 127.93 205.03 0.00 0.25
Mean 54 128 206 0.0 0.21Dv (xx %): average aerosol droplet diameter at a given percentage (xx) of thecumulative volume, for example a value of Dv (10%) = 30.93 mm for the test itemno. 1 (open sieve) means that 10% of all droplets (volume share) had diameters<30.93 mm; 2Cv: average cumulative volume at a given droplet diameter, forexample a value of Cv (at 10.44 mm) = 0.82% for the test item no. 1 (open sieve)means that 0.82% of all droplets (volume share) had diameters <10.44 mm;3Numbers are an average of five measurements.
A B
Figure 3. Analysis of size, shape and aggregation state of SAS particles in the raw material by transmission electron microscopy. A. Besides singleparticles, the state of aggregation and agglomerate on can be seen with lower resolution (1:250,000). The whole bar is 100 nm and one segment of itis 20 nm. B. With higher resolution, the size of the individual particles becomesmore visible (1:560,000). The whole bar is 50 nm and one segment ofit is 10 nm.
K. Michel et al.
smaller size (larger surface area) reached higher maximumsilicon dioxide concentrations (2.7 mmol/l). For all SAStypes, the saturation concentration was reached withinseveral hours (~50 h). The authors concluded that smallamounts of silicon dioxide nanoparticles should be quicklydissolved in a biological environment such as extracellularlung fluid (Roelofs & Vogelsberger 2004).
Summary of physico-chemical properties and possibleimplications for hazard assessmentAll types of SAS share the same chemical composition, aprimary particle size in the nanometre scale and a strongtendency to form aggregates and agglomerates in a dry stateas also demonstrated for the raw material described here.Moreover, free silanol groups at the surface of all those typesof non-modified SAS render them hydrophilic. Size, state ofaggregation and surface characteristics largely determine theproperties of SAS and justify treating the different types as onesubstance. With regard to their behaviour, there are
indications that colloidal SAS dissolves in biological fluids(Roelofs & Vogelsberger 2004). Therefore, it can be assumedthat the toxicological profile of various forms of SAS iscomparable. This has been confirmed by a review paperon the mode of action of SAS published recently (Fruijtier-Pölloth 2012). Based on these considerations, most of thepublished data (ECETOC 2006; OECD 2004) on hazardouseffects of SAS are considered to apply also to the hazardassessment of the colloidal SAS used in the glass cleaner.
Hazard assessment of SASToxicological profileThe toxicological profile of SAS has been described in varioussummary reports (CIR 2009; DFG 1989; ECETOC 2006;OECD 2004). It has been evaluated as food additive for itssafety by the Joint FAO/WHO Expert Committee on FoodAdditives (WHO 1974) and, moreover, has a long history ofsafe use in different applications.
Since the described glass cleaner involves colloidal SAS, thefocus has been on data related to this morphology. It must benoted that crystalline silicon dioxide (quartz), for which pul-monary diseases like silicosis, chronic bronchitis and lungcancer are well known (IARC 1997), has significantly differentproperties. An initial literature search (Figure 2)with the searchterms “silica” OR “silicon dioxide” OR “SiO2” resulted in64,600 hits, demonstrating a huge amount of available databutnot yetdifferentiated for thevariousexisting forms.Narrow-ing down the search to amorphous silicon dioxide forms,nanoscale material and specific end points largely reducesthe number of hits. Evidence shows that the overall toxicityof SAS is low. SAS is not classified as dangerous followingthe criteria of the EU Regulation on the “Classification, Label-ling and Packaging of Substances and Mixtures” (EU 2008c;ECETOC 2006; EKA Chemicals AB 2010).
Toxicokinetics. Regarding adsorption, deposition and elim-ination of SAS it has been reported that there is littleaccumulation in the body, as this substance is eliminatedby dissolution in the lung fluid, excreted in the faeces oreliminated via urine in animals and humans (OECD 2004).Although no skin penetration data for pure SAS are avail-able, data for silicon dioxide-coated particles indicate thatpenetration through skin for such particles is unlikely
0
5
10
15
20
0.1 1 10 100 1000 10000
Vol
ume
(%)
Size (d.nm)
Size distribution by volume
Record 24: Amorphous silicon dioxide
Figure 4. Particle size distribution of the raw material by dynamic light scattering.
0 0.25 0.50 0.75 1.00µm
0
0.25
0.50
0.75
1.00
Figure 5. Analysis of the colloidal SAS applied on a glass slide byatomic force microscopy.
Risk assessment of SiO2 in a cleaner
(Gamer et al. 2006). This might be due to the chemicalcomposition and surface properties. The hydrophilic char-acter of uncoated SAS does not favour penetration. It couldbe demonstrated by in vivo experiments with SAS andsubcutaneous application in rats that even if penetrationhappened, the substancewould be eliminated up to approx.97% within 6 weeks (pyrogenic SAS, 30, 40 or 50 mg asdispersion in water or 0.5% Tween or as dry powder),meaning that it is subject to dissolution and removalfrom the body (ECETOC 2006). The skin is thus not con-sidered a relevant portal of entry of hydrophilic SAS. This isalso supported by various publications on skin penetrationof other nanoparticles, mainly zinc and titanium nanopar-ticles, some coatedwith silicon dioxide orwith hydrophobicmaterial, which suggest that such particles do not penetratethrough the stratum corneum and epidermis and donot reach living tissue in the deeper regions of the skin(Butz 2009; Gamer et al. 2006; Mavon et al. 2007;Pfluecker et al. 2001).
Acute toxicity, irritation and skin sensitisation. The acute oraland dermal toxicity of SAS is low (LD50, oral, rat > 2000 mg/kgbw, LD50, dermal, rabbit > 5000 mg/kg) (OECD 2004). Followinginhalation exposure of rats to the highest technically feasibleconcentrations of 140 to ~ 2000 mg/m3 SAS, no lethal effectswere observed (OECD 2004). SAS is not considered a skinor eye irritant (ECETOC 2006; OECD 2004). There is noevidence of skin sensitisation caused by SAS in workersover decades of practical experience (OECD 2004). In aguinea pig sensitisation study of silicon dioxide no effectswere observed (CIR 2009). Based on its structure and phy-sico-chemical properties it is not expected that SAS causesskin sensitisation (ECETOC 2006). The information on acutetoxicity, irritation and skin sensitisation is also in agreementwith data provided by the supplier (EKA Chemicals AB 2010).
Repeated dose toxicity. Systemic toxicity after repeated appli-cationofSAScouldnotbedetected invariousstudies (ECETOC2006; OECD 2004). The inhalation of respirable particles ofSAS produced a time- and dose-related local inflammationresponse of the lung tissue in animal studies (OECD 2004).However, it was observed in experimental investigations thatthese responses are transient and reversible after terminationof exposure and during the recovery periods, presumably dueto a better lung clearance and elimination based on anincreased solubility compared with quartz (Arts et al. 2007;Johnstonetal. 2000;Mergetet al. 2002;Warheit etal. 1995). Thecomparison of different forms of SAS (pyrogenic, precipitatedand gel, agglomerates of 1–4 mm in the test atmospheres) in a5-day inhalation study revealed that differences were limitedand confined to thefirst-daypost-exposure (Arts et al. 2007). Ina subchronic 13 weeks inhalation toxicity study with SAS andquartz dust in rats, the SAS forms (precipitated and pyrogenic,meanprimaryparticle sizesof12and18nm,sizedistributionofagglomeratesbetween1and120mm) resulted inaqualitativelycomparable effect and a complete clearance from the lungsafter exposure in contrast to the crystalline quartz (Reuzel et al.1991). Another comparison of the effects of SAS includingthe colloidal form (mass median aerodynamic diameter
3–4mm)inshort-terminhalationexperimentswithratssupportthese findings (Warheit et al. 1995). Fruijtier-Pölloth (2012)summarised that none of the SAS forms, including colloidalnanosized particles, were shown to bioaccumulate and alldisappear within a short time from living organisms by phys-iological excretionmechanismswith some indications that thesmaller the particle size, the faster the clearance is.
There is no evidence of long-term respiratory healtheffects in workers employed in manufacturing of SAS (ECE-TOC 2006). In Germany, the occupational exposure limit forthe inhalation of SAS is 4 mg/m3 total dust for 8 h (AGS2006). Like with other particulate matter of small size,inhalation of larger quantities may lead to health effectsas observed with other poorly soluble, inert ultrafine dusts.Overload effects can occur via deposition, and subsequentlyinflammatory processes can take place in the lung. At con-centrations up to 100 mg/m3 as measured at a productionand packaging site, no adverse effects could be observedwith persons who were exposed to varying concentrations ofSAS dust at the workplace and who were regularly checkedfor their health status over 12 years (DFG 1989). Moreover,no risk of teratogenicity is to be expected within the obser-vance of the occupational exposure limit. With regard toreproduction, investigations in experimental animals led tothe conclusion that prolonged exposure to SAS is notexpected to harm the reproductive performance or embry-onic/fetal development (OECD 2004). Although there issome uncertainty with regard to substance characterisationin the available studies, the conclusion was drawn by theOrganisation for Economic Co-operation and Development(OECD) based on the available weight-of-evidence.
Genotoxicity and carcinogenicity. As reviewed by OECD(2004) and by ECETOC (2006), the overall evidence fromexisting studies indicates that SAS is not genotoxic andunlikely to be carcinogenic in humans. In particular, SASdoes not induce mutations either in vitro or in vivo instandard methods (OECD 2004). This is also in agreementwith data provided by the supplier (EKA Chemicals AB2010). Colloidal SAS has been investigated in a Comet assaywith 3T3-L1 fibroblasts and as a result, no significantgenotoxicity was observed under the described test condi-tions (Barnes et al. 2008). Based on negative results inlong-term oral feeding studies of rats and mice and basedon epidemiological experience, there is no evidence of acarcinogenic potential arising from exposure towards SAS(OECD 2004).
Investigations addressing specific properties of nanoparticles.As reviewed recently (Napierska et al. 2010; Jin et al. 2009),several studies explicitly addressing effects discussed as rele-vant fornanotoxicity, like increasedcytotoxicity, inflammation,oxidative stress or formation of reactive oxygen species, havebeen conductedwith various specifically designed amorphoussilicon dioxide nanoparticles, sometimes explicitly describedas “nanosized”. Some of thesematerials are very similar to thecolloidal SAS assessed in this study; others have altered prop-erties due to a different morphology (e.g. mesoporous silicondioxide) or chemicalmodifications (surface coatings). Overall,
K. Michel et al.
the toxicity of SAS nanoparticles in these studies seems to below in vitro and in vivo (Jin et al. 2009). However, a couple ofin vitro studies indicated that specific SAS nanoparticles wereable to exert altered effects in cellular systems. It was assumedthat the surface properties of the silicon dioxide particlescontribute decisively to the observed biological effects; limita-tions of the original studies weremainly caused by insufficientsubstance characterisation and use of non-validated test pro-tocols (Napierska et al. 2010). In addition, such tests weremostly performed with cancer cell lines which are deviatingsignificantly from the normal physiological situation and arethereforeconnectedwithuncertainty regarding their relevancefor human health and need careful interpretation. Investiga-tions with primary cells or in vivo studies, which would allowan extrapolation to the physiological situation in humans withlessuncertainty, arepublished less frequently.Theauthorsandothers have shown previously that responses of primary cells(e.g. oxidative stress) can be considerably different comparedwith cell lines (Albrecht et al. 2009). Most relevant to the riskassessment are studies that directly compare in vitro within vivo effects, or include valid controls and/or benchmarksubstances to allow for a better judgment on the physiologicalrelevance to humans and to provide a solid data base tocorrelate doses and effects.
As reviewed in a recent study, the mode of action of thegroup of SAS has been analysed by in vitro models andmechanistic studies (Fruijtier-Polloth 2012). It was con-cluded that although physical and chemical interactions ofSAS with cell surfaces can result in signalling responses andinflammatory responses after exposure to high doses, thereis no evidence for a novel, hitherto unknownmode of action.
Ecotoxicological profileThe acute toxicity of different types of SAS (functionalised andnon-functionalisedsurfaces,<5mmparticle size)againstdiverseaquatic organisms was reported by ECETOC (2006) to be in therange of »1000 and »10,000mg/l, respectively, showing that nosignificant aquatic toxicitywas determined. Because no specificinformation about the particle size of the material tested isprovided, these data are primarily considered as supportive foran environmental risk assessment. Notably, this range is alsocongruent with information from the supplier of the colloidalSAS used in the glass cleaner (EKA Chemicals AB 2010).
In literature, some studies are available that focus ontoxicity to environmentally relevant organisms, such as bac-teria, plants, daphnia and fish (e.g. Heinlaan et al. 2008;Hund-Rinke & Simon 2006; Oberdörster et al. 2006). Theecotoxicological properties are largely influenced by thesurface properties of the material and environmental factorssuch as pH, organic carbon content and ionic strength of themedium.
The inhibitory effect of silicon dioxide nanoparticles(advertised particle size 14 nm, actual particle size in sus-pension 205 nm) on themultiplication of the bacteria Escheri-chia coli and Bacillus subtilis was studied by Adams et al.(2006). Multiplication of B. subtilis was inhibited by 84 ± 9.9%at 2000 mg/l and 99 ± 1.8% at 5000 mg/l after 14–20 hincubation, while the inhibition was lower for E. coli (48 ±8.5% at 5000 mg/l). However, inhibition was obtained
in culture media optimised for the multiplication andmight not be representative for natural systems with otherinfluencing factors.
Van Hoecke et al. (2008) studied the uptake of colloidalSAS by algae by electron microscopy and found that it isadsorbed to the algal surface but not internalised. Theopposite was observed by Fujiwara et al. (2008) who foundSAS particles incorporated into the test organisms. In par-allel, they found strongly size-dependent effect concentra-tions in the low gram/litre range. However, due to thedissolution processes of SAS it can be anticipated that theparticles will not be stable within the cell over time.
Acute and chronic ecotoxicity of SAS against algae werestudied extensively (Van Hoecke et al. 2011; Van Hoecke et al.2008; Wei et al. 2010). The green algae Scenedesmus obliquuswas exposed to silicon dioxide particles of 10–20 mm diam-eter and showed low toxicity responses on growth rate with anErC20 of 388 mg/l after 72 h (216 mg/l after 96 h) VanHoecke et al. (2008) studied ecotoxicity of commercial col-loidal SAS in suspensions (particle size: 12.5–27 nm) againstPseudokirchneriella subspicata and found 10-fold higher toxi-city responses at ErC20 of 37 mg/l (no observed effect con-centration (NOEC) = 22 mg/l). The effects were correlatedwith a significant decrease of chlorophyll content (VanHoecke et al. 2008; Wei et al. 2010). It was therefore suggestedthat the toxic effects were related to the large specific surfacearea of the nanoparticles and hence an inhibitory effect due tolight shading. It should further be taken into considerationthat colloidal SAS is able to bind earth alkaline ions by ionexchange mechanisms (Karami 2009; Suda et al. 1999). Thedepletion of essential nutrients (e.g. magnesium) may there-fore also be a factor explaining the observed toxicity ofcolloidal SAS on chlorophyll contents (Van Hoecke et al.2008; Wei et al. 2010). A summary of algal toxicity data isshown in Table III.
Supplier information of the colloidal SAS used in glasscleaner indicates the highest ecotoxic potential against algae(EKA Chemicals AB 2010). Hence, it appears adequate to relyon algae for the derivation of a predicted no effect concentra-tion for theaquatic environment (PNECaqua) because this is theonly trophic level for which data on the ecotoxicity of well-characterisedcolloidal SAS for aquatic organismsareavailable.Due to different test designs, data on algal toxicity show verydiverse values ranging from NOEC and EC20 values betweenabout10mg/lup to farmore than1000mg/l.For thepurposeofthis risk assessment a weight-of-evidence approach has beenchosen. Taking into account that the toxicity was significantlyreducedbynaturalorganicmaterial undernatural conditionsareasonable worst-case acute toxicity to algae (ErC50) is higherthan100mg/l.Byapplyinga safety factorof1000aconservativePNECaqua of 0.1 mg/l is derived based on acute studies.
Exposure assessment for the productionof the glass cleanerGeneral aspectsThe glass cleaner formulation is a liquid product which isproduced in a batch process with a volume of ten tons perbatch. On average 6–10 batches are produced per day onapproximately 50 days per year. As the nanoparticles make
Risk assessment of SiO2 in a cleaner
up 0.09% (w/w) of one batch, the amount of silicon dioxidehandled at the production facility can be calculated to be90 kg/day and 4.5 tons/year, respectively. The rawmaterial isprovided as liquid dispersion and is pumped into the batch.All formulation steps take place in closed process operations.
Human exposureNo release of nanoparticles from the closed system is expectedto occur at any step of the formulation assuming well main-tenance, no opening of the system during the process andexclusion of accidental release situations. Thus, exposure viathe inhalative,dermalororal route isnegligible forworkersanddoes not need to be assessed in more detail. As a precaution,general workplace safety measures (protective clothing) areapplied and the production is managed under a certifiedqualitymanagement systemwith regular inspections ensuringthe fulfilment of all requirements.
Environmental exposureAccording to the generic emission estimates of the sectororganisation of the cleaning product manufacturers, 0.2% ofthe rawmaterials (and thus of colloidal SAS) is emitted to theenvironment due to regular cleaning of mixing and packag-ing equipment. The washings are released to the wastewater.The emissions of SAS from production of the glass cleanertherefore amount to 0.18 kg/day. Taking into account thechemical properties of SAS and the abundance of silicondioxide in the environment, the amount released by the glasscleaner production can be neglected.
During recent years, the fateof silicondioxidenanoparticleshas been studied in both, the wastewater and soil compart-ments (Changet al. 2007; Jarvie et al. 2009; Lecoanet et al. 2004;Wiesner et al. 2009). Similar to its ecotoxic behaviour, theoverarching conclusion of all these studies is that the fateand mobility of a nanoparticle is significantly influenced byits surface properties (e.g. coating material, surface charges,etc.). The stability of SAS in solution strongly depends on pH,ionic strength and the natural silicon dioxide concentration inthe environment.
While silicon dioxide nanoparticles coated with non-ionicsurfactants are efficiently removed during sewage treatment(>75%), non-coated particles almost quantitatively passedthe sewage treatment without removal. Jarvie et al. (2009)
and Chang et al. (2007) found that the 1–5 nm particle fractionof non-functionalised silicon dioxide nanoparticles wereeffectively coagulated by treatment with polyaluminium.An elimination of about 50% was observed. For quantitativeexposure estimation (EUSES model), it is conservativelyassumed that the sewage treatment eliminates 10% of SAS.The estimate for PEClocal for the production amounts toapproximately 10 mg/l.
Exposure assessment for the consumer useof the glass cleanerGeneral description of use conditionsThe average use of glass cleaners in German householdshas been investigated in a market research study (HenkelAG & Co. KGaA 2005). It was shown that most frequentlywindows are cleaned approximately three to four times peryear. For consumers’ convenience, glass cleaners areoffered as sprays in trigger bottles. Consumers usuallyspray the formulation onto the dirty surface with a fewstrokes. In doing so the spray aerosol is directed away fromthe human body. Cleaning cloths are used to manuallywipe the windows.
As there is sedimentation of the larger sized droplets, onlysmaller droplets remain in the spray mist in the air aroundthe consumer. As a worst-case scenario, it can be assumedthat the product is applied in a small and enclosed roomwitha low ventilation rate. Usually, however, the ventilation rateis expected to be high due to opening of the windows. Thecleaning cloths are usually put in the washing machine aftera few to several cleaning events. Alternatively, cloths may bedisposed with household waste. Empty plastic bottles arerecommended to be recycled or they are disposed of ashousehold waste.
Human exposureDuring the cleaning event, the consumer is exposed towardsthe spray atmosphere and towards the product remaining ona cleaning cloth. This might result in a possible inhalativeand dermal exposure with the product and the raw materialscontained. Moreover, an indirect oral exposure cannot beexcluded due to a possible migration of the substancesfrom the surface of a cleaned kitchen countertop to non-packaged food. Accidental exposure can happen during
Table III. Summary of literature data on the algal toxicity of SAS.
ReferencesParticlesize (nm) EC20 NOEC Remark
Wei et al. (2010) 10–20 48 h 144 mg/l72 h 388 mg/l96 h 216 mg/l
Concentration-dependent chlorophyll reduction
Van Hoecke et al. (2008) 12.5 72 h 20 mg/l Plateau toxicity 50% growth reduction
unintended use resulting in oral or dermal exposure(detailed calculations not shown). As skin penetration ofSAS is unlikely based on current knowledge (chapter 3.2.1(Hazard assessment of SAS)), skin contact will not lead tosystemic exposure. Regarding the current application themost important exposure route is via the lung.
Inhalation exposure may occur when the silicon dioxidecontained in aerosol droplets reach the breathing zone ofconsumers during the actual use of the product. Measure-ments of size distribution of the aerosol droplets containingthe complete product formulation were performed in orderto evaluate which fractions of the aerosol are inhalable andwhich are respirable. Results of the size distribution mea-surements of aerosol droplets generated during the use of aglass cleaner formulation are shown in Table II (two inde-pendent repeats). Measurements were performed by laserdiffraction analysis with open and closed sieve at the triggerbecause consumers can be exposed towards a spray aerosol(open sieve) and foam aerosol (closed sieve).
With the spray function 50% of the aerosol droplets(volume share) had a droplet size smaller than 95 mm forFormulation 1 and 75 mm for Formulation 2. The meanfraction of aerosol droplets with a size of not more that 10 mmwas 0.7% (average cumulative volume) for Formulation1 and 1.1% (average cumulative volume) for Formulation2. No droplets with a diameter below 4 mm could be detectedfor both formulations.
With the foam function the situation was comparable.Fifty percent of the aerosol droplets (volume share) had adroplet size smaller than 127 mm for Formulation 1 and128 mm for Formulation 2. The mean fraction of aerosoldroplets with a size of not more that 10 mm was 0.2%(average cumulative volume) for both formulations. Nodroplets with a diameter below 4 mm could be detected.
Besides determination of the droplet size, the airborneconcentration of SAS during one spray event was modelledwith the software ConsExpo�. It takes into account theconcentration of non-volatiles in the product and the dropletsizes which determine how long particles stay in the air. Thecalculation of the indoor inhalation exposure was done forthe spraying process because it is to be assumed that theamount of SAS released to the air is higher for this eventcompared with the application of foam. Under the assump-tions mentioned above (intended use), a mean concentra-tion of 0.002 mg/m3 of SAS in the surrounding breathingzone of the consumer during one cleaning event was cal-culated as point estimate. The peak concentration wascalculated to be 0.035 mg/m3 shortly after spraying theproduct on the surface and rapidly decreased towardszero after 3 min exposure time (Figure 6). The air concen-tration calculated for an accidental setting (spraying towardsexposed person) resulted in 0.044 mg/m3.
The exposure concentration related to a frequent use ofthe cleaner, for example in professional settings, was notcalculated separately as the number of exposure eventsincreases while the exposure concentration of SAS in thesurrounding remains the same.
Based on physico-chemical properties of the chemicalsubstance, it is assumed that there will be no release of
isolated nanoparticles from the glass into the surrounding airin case of a later mobilisation of dirt.
Environmental exposureOf the worldwide consumed SAS (pyrogenic and precipi-tated) which was reported to account for >500,000 tons in2002 (OECD 2004) the colloidal SAS comprises only a smallfraction. Quantitative data on colloidal SAS use in WesternEurope are provided in the Chemicals Handbook up to theyear 2007 (Lauriente & Yokose 2008). While the total amountused is reported to be 18,000 tons/year mainly representingapplications in the pulp and paper, textile and beverageindustry, the uses for domestic cleaning purposes are notexplicitly mentioned due to minor significance. An exactnumber of the fraction released to the aquatic environmentis not known. However, because of its functional role in theabove-mentioned industrial applications it is assumed thatthe majority of SAS does not enter the environment butremains in the processes. Hence, as a conservative estima-tion it is assumed that in maximum about 10% of the SASreported in total will eventually enter the environmentleading to an amount of 1800 tons/year.
As a conservative estimation the use of a glass cleanerformulation for consumer application with 0.09% (w/w)silicon dioxide will lead to a Europe wide release of lessthan 10 tons/year. This, therefore, represents less than 1‰ ofthe total annual consumption. However, to provide a con-servative description of the substance emissions into theenvironment, EUSES exposure calculations on wide disper-sive uses are based on a total of 1800 tons/year.
Considering the use in glass cleaners it may be assumedthat the contained colloidal SAS is mainly adsorbed on theglass surface. Weathering processes may lead to dissolutionand a potential rinse-off over time leading to some exposureto soil in the surrounding of a building and/or (indirectly) tothe aquatic environment. It can be assumed that this way ofexposure does not lead to a significant entry of nanoparticlesin the soil environment. Another exposure path can beconsidered down the drain to wastewaters, eventually lead-ing to emissions into natural rivers via the sewage systemsand partly to soil via sewage sludge applications on agricul-tural soil. Due to the product application the exposure pathto enter the aquatic environment is dominant.
Based on the assumptions made, a regional backgroundpredicted environmental concentration (PECregional) of SAS<1 mg/l is calculated. From the wide dispersive use of theglass cleaner a local concentration of SAS in surface water iscalculated to be approximately 10 mg/l (PEClocal).
Currently, there are no accepted methods to screen forthe bioaccumulation potential of nanoparticles. However,due to the dissolution behaviour of SAS in natural media nosignificant bioaccumulation potential may be assumed.
Risk assessmentRisk assessment regarding the productionof the glass cleanerHuman risk assessment. The production of the glass cleaner isa wet process and production lines are contained. At theworkplace exposure to colloidal SAS can be regarded as
Risk assessment of SiO2 in a cleaner
negligible, provided that there are no unintended leakages. Itis controlled by suitable technical and general workplacesafety standards which are applied as a matter of hygieneand responsible care. On the basis of a thorough consider-ation of exposure and taking into account the low toxicity ofSAS, a risk is considered to be low at the production even incase of occasional contact to the skin, since skin penetrationis not expected.
Environmental risk assessment. The PEClocal for production(10 mg/l) is considerably below the PNEC (0.1 mg/l). Inaddition, it is considerably below the naturally occurringconcentrations of dissolved silicon dioxide in larger Germanrivers, which typically range between 1 and 10 mg/l (e.g.Ladwig 2012; Wind et al. 2008). The environmental risk fromthe production of the glass cleaner formulation with colloidalSAS is thus considered to be low.
Risk assessment regarding the consumer useof the glass cleanerHuman risk assessment (focus on inhalation). The risk assess-ment for the inhalative route during application of the glasscleaner is demonstrated in detail as this is of highest rele-vance for the consumer.
As described before, the hazard of SAS in general isrelatively low especially compared with quartz. It is wellknown that SAS does not lead to persistent toxicologicaleffects in the lung as long as overload conditions regardingthe amount of dust in the lungs are avoided. One majoraspect is therefore that the exposure is also low.
In general, the fraction of total airborne particles whichreaches the human airways depends on the properties of theparticles, on air speed and direction close to the body, as wellas on breathing rate and human physiology. The likeliness ofinhalation of particles, their deposition, tissue reactions andexhalation differs strongly between individuals. Conventionshave been set up for particle size-dependent sampling ofairborne particles (CEN 1993). Those conventions are used
to evaluate the likeliness of inhalation of airborne aerosoldroplets depending on their diameter. Considering the dis-tribution of droplet size as determined for the glass cleanerformulation about half of all aerosol particles (spray andfoam) would not be inhalable according to the conventions(>100 mm). A fraction of 1.1% as maximum of the productsprayed and 0.2% of the foam have droplets with diametersbelow 10 mm (average cumulative volume). It can be pre-dicted that 50% of those droplets might reach the thoracicregion of the lungs (<10 mm). In this region, mucociliaryclearance mechanisms are in place. It is very unlikely thatdroplets from the glass cleaner spray will be deposited in thealveolar region, as no droplets with a diameter below 4 mmhave been detected in the samples analysed. Even if someindividual droplets of this fraction were small enough toreach the alveoli and were not exhaled, SAS could be clearedby alveolar macrophages and by dissolution.
A typical particle size distribution of SAS has already inthe past included a certain fraction of particles at the nano-scale (DFG 1989). From human experience it is known thateven after repeated exposure towards SAS dust in a concen-tration up to 100 mg/m3, no negative health implications forworkers in industry have been observed. As mentionedbefore, an occupational exposure limit of 4 mg/m3 hasbeen derived for colloidal SAS for an exposure duration of8 h and for the inhalable fraction of dust (defined forparticles with a size below 100 mm) (AGS 2006; DFG 1989).
For a quantitative risk assessment for cleaning of windowsthe calculated amounts (0.002 mg/m3 during one cleaningevent with a peak concentration of 0.035 mg/m3 in the firstminute, and 0.044 mg/m3 in an accidental situation, allbased on an inhalation cut-off diameter of 100 mm) arecompared with the existing specific occupational exposurelimit (4 mg/m3). The estimated concentrations are in theorder of magnitude of 100 lower. Although this threshold hasbeen set up for the workplace situation, it is considered to besufficiently conservative also for the private household as itcovers a timeframe of 8 h and the inhalable fraction. The
Air concentration
0
0.005
0.01
0.015
0.02
0.025
0.03
0.035
0.04
0 1 2 3 4 5 6 7 8 9 10
Time (minute)
Con
cent
ratio
n (m
g/m
3 )
Figure 6. Calculated air concentration of SAS during consumer exposure towards the glass cleaner spray.
K. Michel et al.
usual duration of the cleaning process is much lower andaccidental situations are exceptional.
As the colloidal SAS is not available in a dusty form, asaerosol droplets are larger than 4 mm in diameter and, thus,not regarded as respirable and as the concentration of SAS inthe surrounding atmosphere of the person using the productis far below the threshold value assessed to result in noadverse health implications, it is concluded that the risk ofapplying the glass cleaner with colloidal SAS is very low.
Environmental risk assessment. In the current analysis theestimations were focused on the release of SAS particles intothe aquatic environment due to its use in products. Althoughonly a very small amount of colloidal SAS is used in hardsurface cleaning products compared with other applications, aconservative assumption on total emissions was made thatincludes the application in domestic hard surface cleaning butalso other applications leading to environmental exposure.Based on estimates the PEC of environmentally relevant SAS(PECregional 1 mg/l, PEClocal 10 mg/l) can be calculated to bemuch lower than the PNEC (0.1 mg/l). Further to that due tothe natural dissolution and re-deposition processes of silicondioxide, no long-term stability of SAS is anticipated underenvironmental conditions. Taking into account the uncertain-ties that remain and under the conservative assumptionsmade for tonnage, fate and ecotoxicity of colloidal SAS norisk is indicated for the aquatic environment.
Discussion
Risk assessment methodologyThis study presents the human and environmental riskassessment of colloidal SAS (= amorphous silicon dioxidenanoparticles) in a glass cleaner. Regarding the appropriatemethodology for risk assessment of nanomaterials there is anongoing debate on how this topic can be best approached(Holsapple et al. 2005; SCENIHR 2009). It has been con-cluded by SCENIHR that there is currently no generallyapplicable paradigm for nanomaterial-specific hazard iden-tification, and a case-by-case approach would be the appro-priate choice for risk assessment (SCENIHR 2009). Inaddition, Baier-Anderson et al. (2007) have suggested aframework to address areas of incomplete or uncertaininformation by using reasonable assumptions leading toappropriate risk management practices. This approach is ageneral principle not limited to the risk assessment ofnanomaterials and regulatory guidance has been providedpreviously reflecting the state-of-the-art in risk assessment(ECHA 2008, 2010b, c).
Metrics for nanomaterialsThe metrics currently used in risk assessment are usuallybased on mass to express exposure and toxicological effects.In the area of nanotoxicology a scientific debate is ongoing onwhether another metric like particle number or surface areashould be added (Bouwmeester et al. 2011; Warheit et al.2007). This is, for example, based on the observation oftoxicological effects like inflammation, which are likely tobe related to particle surface area (Donaldson & Tran 2002;
Höhr et al. 2002). Although there are currently no definitiveconclusionson thebestmetric, it is suggested that thephysico-chemical description should be detailed to allow an expres-sion of dose-response in the different metrics (Hankin et al.2011). In the case of SAS, it needs to be considered thatavailable data are partly reaching back to the 1960s/70swhen dose was used to be expressed in mass and detailson particle numbers or surface area were not given. As thesubstance is not a new nanomaterial but has always been in ananostructured form, the existing risk assessments and expo-sure values are still valuable in the current discussion onnanoparticles. In a recent study (Fruijtier-Pölloth 2012), it isdescribed that, in addition, none of the newly available datagive any evidence for a novel, hitherto unknown mechanismof toxicity that may raise concerns with regard to humanhealth or environmental risks. Thus, to allow for comparabil-ity, the mass-based approach is considered a valid option inthis investigation.
Hazard identificationThe OECD Working Party on Manufactured Nanomaterialshas reviewed the available standard test guidelines for haz-ard identification and has shown that principally the testguidelines are suitable also for nanomaterials but might needmodification in some cases (OECD 2011). This conclusionsupports the validity of existing data on SAS as long as thestudy design and performance fulfil accepted and scientificstandards.
Itneeds tobeacknowledged that the studies referring toSASoften lack a detailed specification of the particle size distribu-tion though it is known that a fraction of particles at thenanoscale is usually contained. An exact quantitative compar-ison between studies with different materials is thereforepossible only to a limited extent. Since the parameters andmethodologies for nanomaterial characterisation are gettingmore refined and standardised (Bouwmeester et al. 2011;NanoCare Project Partners 2009; Schulze et al. 2008), thissituation is expected to improve in the future. The same holdstrue for kinetic analyses. Further research may provide moreinsight into size-dependent penetration properties of silicondioxide through various biological barriers and dissolution aswell as excretion kinetics. Some recent cell culture studies inthe area of nanotoxicology are questionable regarding theirphysiological relevance. Critical factors are the inclusion ofappropriate controls and benchmarks, selection of physiolog-ically relevant concentrations, non-speculative interpretationof effects and development of standardised and validatedprocedures (Bouwmeester et al. 2011; NanoCare ProjectPartners 2009).
Exposure assessmentRegarding the tools for exposure assessment ConsExpo� andEUSES are widely accepted for regulatory purposes (ECHA2010a, c). By applying default as well as worst-case assump-tions exposure estimates were derived. The spray model wasdeveloped on the basis of the results of experimental work.Acknowledging the fact that some parameters are difficult toestimate, the reliability of the default values is categorised inthe software documentation and taken into account.
Risk assessment of SiO2 in a cleaner
Although measured data would generally be preferred overmodelled data to account for the most realistic situation, awell-established mechanism of exposure modelling allowsquantifying exposure because the results are conservative,which means real conditions are overestimated. Measuringsingle airborne nanoparticles in experimental settings is stillan issue for research. Approaches for workplace settingshave been published (Kuhlbusch et al. 2011), however, itneeds to be considered that an air concentration of SAS inprivate settings when applying the glass cleaner is muchlower than potential dust concentrations at workplaces.Highly sensitive measurement devices and a reliable differ-entiation against the background particle burden would beneeded, but are currently not available as standardisedtechniques.
Applicability of risk assessment approachIt can be argued that the risk assessment approach reportedhere is applicable for the colloidal SAS in the present appli-cation, because already under the conservative assumptionsof the first tier and the available information on the substanceno risk was indicated neither for man nor the environment.However, it should be kept in mind that such an approachmay not necessarily be applicable to all nanomaterials asthese are a very heterogeneous group of substances and areused in a variety of applications. From the current knowledge,the authors conclude that risk assessments for nanomaterialsshould, therefore, be done on a case-by-case basis.
Conclusions
This analysis takes into account information on human andenvironmental hazards and modelled exposure data basedon state-of-the-art methodologies. It demonstrates that theuse of colloidal SAS does not pose a risk for humans andthe environment for the intended use in a glass cleanerformulation based on the available weight-of-evidence. Theapplied risk assessment strategy was built on conservativeassumptions to allow for consideration of uncertainties. Insummary, it proved to be a useful methodology for a rea-sonable risk evaluation of amorphous silicon dioxide nano-particles in this case study.
Acknowledgements
The authors would like to thank Doris Gesterkamp andElke Lehringer for assisting in the literature search and foreditorial support; Michaela Berchter, Burkhard Eschenand Hans-Juergen Schwark for performing analytical mea-surements; Lothar Kintrup, Thomas Mueller-Kirschbaum,Roland Schroeder, Walter Sterzel, Johannes Tolls andFrederike Wiebel for general support and review of themanuscript. Funding source: The work was funded byHenkel AG & Co. KGaA.
Declaration of interest
The authors are employees of Henkel AG & Co. KGaA. Theauthors state that this did not influence the scientificobjectiveness of the analysis.
ReferencesAdams LK, Lyon DY, Alvarez PJ. 2006. Comparative eco-toxicity of
nanoscale TiO2, SiO2, and ZnO water suspensions. Water Res40:3527–3532.
AGS. 2006. TRGS 900 – Technische Regeln für Gefahrstoffe. Ausschussfür Gefahrstoffe – AGS-Geschäftsführung – BAuA. Online Availableat www.baua.de.Accessed on 13 July 2011.
Albrecht C, Scherbart AM, van Berlo D, Braunbarth CM, Schins RP,Scheel J. 2009. Evaluation of cytotoxic effects and oxidative stresswith hydroxyapatite dispersions of different physicochemical prop-erties in rat NR8383 cells and primary macrophages. Toxicol In Vitro23:520–530.
Alexander GB, Heston WM, Iler RK. 1954. The solubility of amorphoussilica in water. J Phys Chem 58:453–455.
Arts JH, Muijser H, Duistermaat E, Junker K, Kuper CF. 2007. Five-dayinhalation toxicity study of three types of synthetic amorphoussilicas in Wistar rats and post-exposure evaluations for up to3 months. Food Chem Toxicol 45:1856–1867.
Baier-Anderson C, Balbus J, Carberry J, Denison R, Doraiswamy K,Gannon J, et al. 2007. NANO Risk Framework. EnvironmentalDefense – DuPont Nano Partnership. Online Available at www.NanoRiskFramework.com.Accessed on 29 June 2011; 1-102.
Barnes CA, Elsaesser A, Arkusz J, Smok A, Palus J, Lesniak A, et al. 2008.Reproducible comet assay of amorphous silica nanoparticles detectsno genotoxicity. Nano Lett 8:3069–3074.
Borm P, Klaessig FC, Landry TD, Moudgil B, Pauluhn J, Thomas K, et al.2006a. Research strategies for safety evaluation of nanomaterials, partV: role of dissolution in biological fate and effects of nanoscaleparticles. Toxicol Sci 90:23–32.
Borm PJ, Robbins D, Haubold S, Kuhlbusch T, Fissan H,Donaldson K, et al. 2006b. The potential risks of nanomaterials:a review carried out for ECETOC. Part Fibre Toxicol 3:11.
Bouwmeester H, Lynch I, Marvin HJ, Dawson KA, Berges M,Braguer D, et al. 2011. Minimal analytical characterization of engi-neered nanomaterials needed for hazard assessment in biologicalmatrices. Nanotoxicology 5:1–11.
Butz T. 2009. Dermal Penetration of Nanoparticles – What we knowand what we don’t. SöFW J10, 135:30–34.
CEN. 1993. Workplace atmospheres. Size fraction definitions for mea-surement of airborne particles – EN 481:1993. Eur Committee Stand,1–9.
Chang JS, Chang KL, Hwang DF, Kong ZL. 2007. In vitro cytotoxicitiy ofsilica nanoparticles at high concentrations strongly depends onthe metabolic activity type of the cell line. Environ Sci Technol41:2064–2068.
CIR. 2009. Final Report of the Cosmetic Ingredient Review ExpertPanel – Safety Assessment of Silica and Related Cosmetic Ingredi-ents. In: Cosmetic Ingredient Review, Washington, DC.
Dekkers S, Krystek P, Peters RJ, Lankveld DX, Bokkers BG, vanHoeven-Arentzen PH, et al. 2011. Presence and risks of nanosilicain food products. Nanotoxicology 5:393–405.
Donaldson K, Murphy FA, Duffin R, Poland CA. 2010. Asbestos, carbonnanotubes and the pleural mesothelium: a review of the hypothesisregarding the role of long fibre retention in the parietal pleura,inflammation and mesothelioma. Part Fibre Toxicol 7:5.
Dreja M, Noglich J, Guckenbiehl B. 2010. Method for cleaning hardsurfaces using a composition comprising a colloidal silica sol.US7745383.
Dreja M, Noglich J, Josa J. 2004. Self-organized nano-particles forenhanced wetting of hard surfaces. Tenside Surf Det 41:180–186.
Dreja M, Noglich J, Menke R, Plantikow P. 2005. HydrophilierenderReiniger für harte Oberflächen. Patentblatt DE102004019022A1.
DuPont. 2007. DuPont� Light Stabilizer Framework Example –Nanomaterial Risk AssessmentWorksheet DuPont� Light Stabilizer.Online Available at http://www.edf.org/documents/6913_TiO2_Worksheet.pdf.Accessed on 5 July 2011.
ECETOC. 2006. Synthetic Amorphous Silica (CAS No. 7631-86-9) –JACC REPORT No. 51. European Centre for Ecotoxicology andToxicology of Chemicals, Brussels ISSN-0773-6339-51.
ECHA. 2008. Guidance on information requirements and chemicalsafety assessment. Chapter R.10: Characterisation of dose
K. Michel et al.
[concentration]-response for environment. Online Available athttp://www.echa.europa.eu.Accessed on 14 July 2011; 1-65.
ECHA. 2010a. Guidance on information requirements and chemicalsafety assessment Chapter R.16: Environmental Exposure Estima-tion. Online Available at http://www.echa.europa.eu.Accessed on21 July 2011; Ref.: ECHA-10-G-06-EN:1-59.
ECHA. 2010b. Guidance on information requirements and chemicalsafety assessment. Chapter R.8: Characterisation of dose [concen-tration]-response for human health. Online Available at http://www.echa.europa.eu.Accessed on 14 July 2011; Ref.: ECHA-2010-G-19-EN:1-194.
ECHA. 2010c. Guidance on information requirements and chemicalsafety assessment. Chapter R.15: Consumer exposure estimation.Online Available at http://www.echa.europa.eu.Accessed on 21 July2011; Ref.: ECHA-10-G-03-EN:1-59.
EKA Chemicals AB. 2003. Product Data Sheet for amorphous silicondioxide, aqueous colloidal dispersion.
EKA Chemicals AB. 2010. Material Safety Data Sheet for amorphoussilicon dioxide, aqueous colloidal dispersion.
EU. 2004. Directive 2004/10/EC of the European Parliament and of theCouncil on the harmonisation of laws, regulations and administra-tive provisions relating to the application of the principles of goodlaboratory practice and the verification of their applications for testson chemical substances (codified version). Official J Eu Union L50:44–59.
EU. 2008a. Commission Directive 2008/84/EC laying down specificpurity criteria on food additives other than colours and sweeteners.Official J Eur Union L 253:1–175.
EU. 2008b. European Chemicals Bureau, Ispra, Italy. Online Availableat http://ihcp.jrc.ec.europa.eu/our_activities/health-env/risk_as-sessment_of_Biocides/euses.Accessed on 29 July 2011.
EU. 2008c. Regulation (EC) No. 1272/2008 of the European Parliamentand of the Council on classification, labelling and packaging ofsubstances and mixtures. Official J Eur Union L 353:1–1354.
EU. 2011. Commission recommendation of 18 October 2011 on thedefinition of nanomaterial.(2011/696/EU). Official J Eur Union L275:38–40.
Fruijtier-Pölloth C. 2012. The toxicological mode of action and thesafety of synthetic amorphous silica-A nanostructured material.Toxicology 294:61–79.
Fujiwara K, Suematsu H, Kiyomiya E, Aoki M, SatoM,Moritoki N. 2008.Size-dependent toxicity of silica nano-particles to Chlorella kessleri.J Environ Sci Health A Tox Hazard Subst Environ Eng 43:1167–1173.
Gamer AO, Leibold E, van Ravenzwaay B. 2006. The in vitro absorptionof microfine zinc oxide and titanium dioxide through porcine skin.Toxicol In Vitro 20:301–307.
Hankin SM, Peters SAK, Poland CA, Foss Hansen S, Holmqvist J,Ross BL, et al. 2011. Specific Advice on Fulfilling InformationRequirements for Nanomaterials under REACH (RIP-oN 2) – FinalProject Report. British Standards Institution (BSI) RNC/RIP-oN2/FPR/1/FINAL:1-356.
Heinlaan M, Ivask A, Blinova I, Dubourguier HC, Kahru A. 2008.Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteriaVibrio fischeri and crustaceans Daphnia magna and Thamnocepha-lus platyurus. Chemosphere 71:1308–1316.
Höhr D, Steinfartz Y, Schins R, Knaapen AM, Martra G, Fubini B, et al.2002. The surface area rather than the surface coating determinesthe acute inflammatory response after instillation of fine and ultra-fine TiO2 in the rat. Int J Hyg Environ Health 205:239–244.
Holsapple MP, Farland WH, Landry TD, Monteiro-Riviere NA,Carter JM, Walker NJ, et al. 2005. Research strategies for safetyevaluation of nanomaterials, part II: toxicological and safety eval-uation of nanomaterials, current challenges and data needs. ToxicolSci 88:12–17.
Hund-Rinke K, Simon M. 2006. Ecotoxic effect of photocatalytic activenanoparticles (TiO2) on algae and daphnids. Environ Sci Pollut ResInt 13:225–232.
IARC. 1997. Monographs on the Evaluation of Carcinogenic Risks toHumans, Silica. Int Agency Res Cancer (IARC) 68:1–9.
International Organization for Standardization. 2008. Nanotechnolo-gies – Terminology and definitions for nano-objects – Nanoparticle,nanofibre and nanoplate (ISO/TS 27687:2008(E)). In: ISO copyrightoffice.
Jarvie HP, Al-Obaidi H, King SM, Bowes MJ, Lawrence MJ,Drake AF, et al. 2009. Fate of silica nanoparticles in simulated primarywastewater treatment. Environ Sci Technol 43:8622–8628.
Jin Y, Lohstreter S, Zhao JX. 2009. Toxicity of Spherical and AnisotropicNanosilica. Nanomat Life Sci 2:221–244.
Johnston CJ, Driscoll KE, Finkelstein JN, Baggs R, O’Reilly MA,Carter J, et al. 2000. Pulmonary chemokine and mutagenicresponses in rats after subchronic inhalation of amorphous andcrystalline silica. Toxicol Sci 56:405–413.
Karami A. 2009. Study on modification of colloidal silica surface withmagnesium ions. J Colloid Interface Sci 331:379–383.
Kreyling W, Semmler-Behnke M, Möller W. 2006. Health implicationsof nanoparticles. J Nanoparticle Res 8:543–562.
Krug HF, Wick P. 2011. Nanotoxicology: An Interdisciplinary Chal-lenge. Angew Chem Int Ed Engl 50:1260–1278.
Kuhlbusch TA, Asbach C, Fissan H, Gohler D, Stintz M. 2011. Nano-particle exposure at nanotechnology workplaces: a review. PartFibre Toxicol 8:22.
Ladwig N. 2012. Kritische Betrachtung von Eutrophierungstendenzenin der inneren Deutschen Bucht. Berichte aus dem Forschungs- undTechnologiezentrum Westküste der Universität Kiel 47:1–167.
Lauriente DH, Yokose K. 2008. Chemical Economics Handbook.Online Available at: http://chemical.ihs.com/CEH/Public/Reports/766.4000/. Accessed on 15 July 2011.
Lecoanet HF, Bottero JY, Wiesner MR. 2004. Laboratory assessment ofthe mobility of nanomaterials in porous media. Environ Sci Technol38:5164–5169.
Mavon A, Miquel C, Lejeune O, Payre B, Moretto P. 2007. In vitropercutaneous absorption and in vivo stratum corneum distributionof an organic and a mineral sunscreen. Skin Pharmacol Physiol20:10–20.
Merget R, Bauer T, Kupper HU, Philippou S, Bauer HD,Breitstadt R, et al. 2002. Health hazards due to the inhalation ofamorphous silica. Arch Toxicol 75:625–634.
Miretzky P, Conzonno V, Fernández Cirelli A. 2001. Geochemicalprocesses controlling silica concentrations in groundwaters ofthe Salado River drainage basin, Argentina. J Geochem Explor73:155–166.
NanoCare Project Partners. 2009. NanoCare –Health related Aspects ofNanomaterials – Final Scientific Report. Frankfurt: 1–158.
Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH. 2010.The nanosilica hazard: another variable entity. Part Fibre Toxicol7:39.
Nel A, Xia T, Madler L, Li N. 2006. Toxic potential of materials at thenanolevel. Science 311:622–627.
Oberdörster E, McClellan-Green P, Haasch M. 2006. Ecotoxicity ofengineered nanomaterials. In: Nanotechnology for Life Sciences.Weinheim: Wiley-VCH.
Oberdörster G. 2009. Safety assessment for nanotechnology and nano-medicine: concepts of nanotoxicology. J Intern Med 267:89–105.
OECD. 2004. SIDS Initial Assessment Report on Synthetic amorphousSilica and Silicates – CAS 7631-86-9, 112945-52-5, 112926-00-8:Silicon Dioxide; CAS 1344-00-9: Silicic Acid, Aluminum SodiumSalt; CAS 1344-95-2: Silicic Acid, Calcium Salt. In.
OECD. 2011. Nanosafety at the OECD: The First Five Years 2006-2010.Online Available at http://www.oecd.org.Accessed on 14 July 2011;1-16.
Pfluecker F, Wendel V, Hohenberg H, Gartner E, Will T, Pfeiffer S, et al.2001. The human stratum corneum layer: an effective barrieragainst dermal uptake of different forms of topically appliedmicronised titanium dioxide. Skin Pharmacol Appl Skin Physiol14(Suppl 1):92–97.
Poland CA, Duffin R, Kinloch I, Maynard A, Wallace WAH,Seaton A, et al. 2008. Carbon nanotubes introduced into theabdominal cavity of mice show asbestos-like pathogenicity in apilot study. Nat Nanotechnol 3:423–428.
Reuzel PG, Bruijntjes JP, Feron VJ, Woutersen RA. 1991. Subchronicinhalation toxicity of amorphous silicas and quartz dust in rats. FoodChem Toxicol 29:341–354.
Roelofs F, Vogelsberger W. 2004. Dissolution Kinetics of SyntheticAmorphous Silica in Biological-Like Media and Its TheoreticalDescription. J Phys Chem B 108:11308–11316.
Royal Academy of Engineering. 2004. Nanoscience and nanotechnol-ogies: opportunities and uncertainties. The Royal Society - SciencePolicy Section. London; 1–127.
SCENIHR. 2007. Scientific Committee on Newly Identified and Emerg-ing Health Risks. Opinion on the appropriateness of the risk assess-ment methodology in accordance with the technical guidancedocuments for new and existing substances for assessing the risksof nanomaterials. Available at http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_010.pdf.
Risk assessment of SiO2 in a cleaner
SCENIHR. 2009. Scientific Committee on Newly Identified and Emerg-ing Health Risks. Risk Assessment of Products of Nanotechnologies.Online Available at http://ec.europa.eu/health/ph_risk/commit-tees/04_scenihr/docs/scenihr_o_023.pdf.Accessed on 5 July 2011.
SCENIHR. 2010. Scientific Committee on Newly Identified and Emerg-ing Health Risks. Scientific Basis for the Definition of the Term“Nanomaterial”. Online Available at http://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_032.pdf.Accessedon 5 July 2011.
Schulze C, Kroll A, Lehr C-M, Schäfer UF, Becker K, Schnekenburger J,et al. 2008. Not ready to use – overcoming pitfalls when dispersingnanoparticles in physiological media. Nanotoxicology 2:51–61.
Suda S-I, Tashiro T, Umegaki T. 1999. Synthesis of MgO-SiO2 andCaO-SiO2 amorphous powder by sol-gel process and ion exchange.J Non-Crystalline Solids 255:178–184.
US EPA, 2008. Estimation Programs Interface Suite� for Microsoft�Windows,Version4.0 (EPIWEBv4.0) (EPISuite v4.0)Washington,DC,USA.
Van Hoecke K, De Schamphelaere KA, Ramirez-Garcia S, Van derMeeren P, Smagghe G, Janssen CR. 2011. Influence of aluminacoating on characteristics and effects of SiO2 nanoparticles in algalgrowth inhibition assays at various pH and organic matter contents.Environ Int 37:1118–1125.
Van Hoecke K, De Schamphelaere KA, Van der Meeren P, Lucas S,Janssen CR. 2008. Ecotoxicity of silica nanoparticles to the green algaPseudokirchneriella subcapitata: importance of surface area. Envi-ron Toxicol Chem 27:1948–1957.
Warheit DB, Borm PJ, Hennes C, Lademann J. 2007. Testing strategiesto establish the safety of nanomaterials: conclusions of an ECETOCworkshop. Inhal Toxicol 19:631–643.
Warheit DB, McHugh TA, Hartsky MA. 1995. Differential pulmo-nary responses in rats inhaling crystalline, colloidal or amor-phous silica dusts. Scand J Work Environ Health 21(Suppl 2):19–21.
Wei C, Zhang Y, Guo J, Han B, Yang X, Yuan J. 2010. Effects of silicananoparticles on growth and photosynthetic pigment contents ofScenedesmus obliquus. J Environ Sci (China) 22:155–160.
WHO. 1974. WHO (World Health Organization) Food Additives Seriesno. 5 – Silicon Dioxide and certain Silicates. Joint FAO/WHO ExpertCommittee on Food Additives.
Wiesner MR, Lowry GV, Jones KL, Hochella MF Jr, Di Giulio RT,Casman E, et al. 2009. Decreasing uncertainties in assessing envi-ronmental exposure, risk, and ecological implications of nanoma-terials. Environ Sci Technol 43:6458–6462.
Wind T, Steber J, Tolls J. 2008. 50 Years of environmental monitoring atHenkel. Tenside Surf Det 45:144–152.
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