Despite high interest on the use of TiO2 particles and their potential impact following acute and chronic exposure, investigative studies looking at TiO2 absorption in humans have only been reported once, in 2015 [13], since the initial published findings in the year 2000 [12]. Lin Z, Monteiro-Riviere NA, Riviere JE.

3b, c, t2-t10), with both techniques demonstrating a peak of absorption at 6h post ingestion (Fig. As noted earlier, the term persorption has been coined by- and the phenomenon well described by- Volkeimer [7]. In the textile fibres sector, marked TiO2 pigments can, for example, be used to mark special, high-quality fibres, and the products made of them, and protect them against imitation.

One drop of blood (~45l) from the syringe following sampling (i.e. The suspension is set to a pH value of 6.8, freed of water-soluble salts by washing, and dried.

Wash the zinc amalgam column with 100-mL portions of 2 N sulfuric acid until 100 mL of the washing does not decolorize 1 drop of 0.1 N potassium permanganate. In this method, the marker substance can be added to the suspension as an appropriate quantity of a water-soluble compound and precipitated at a given pH value. However, in the recent work, high baseline values appear to have prevented observations on the appearance of Ti in the circulation following ingestion of TiO2 [13].

The invention further relates to a method for producing marked titanium dioxide pigment particles, as well as to the titanium dioxide pigment particles marked in this way. Powell JJ, Ainley CC, Harvey RS, Mason IM, Kendall MD, Sankey EA, et al. The marker substance to be used according to the invention can be added both by doping in the crystal lattice and when coating the surface (hereafter: surface treatment). non-heparinised) was placed on a clean, freshly opened glass slide. This study shows that a fraction of pharmaceutical/food grade titanium dioxide is absorbed systemically by humans following ingestion. The authors would like to acknowledge the UK Medical Research Council (Grant number U105960399) for their continued support. Geraets L, Oomen AG, Krystek P, Jacobsen NR, Wallin H, Laurentie M, et al. TiO2 readily reflects light so particles can easily be detected in complex biological samples using this technique [14]. Intestinal villous M cells: an antigen entry site in the mucosal epithelium.

have shown in humans that measurable increases in total titanium (Ti) levels occur in the blood stream following ingestion of capsules containing TiO2 particles [12]. TiO2 particles within blood) and the levels of Ti measured by ICP-MS was determined using a Spearman correlation test. The marker substances can be added at various points of the TiO2 production process. ], Coated or impregnated woven, knit, or nonwoven fabric which is not [a] associated with another preformed layer or fiber layer or, [b] with respect to woven and knit, characterized, respectively, by a particular or differential weave or knit, wherein the coating or impregnation is neither a foamed material nor a free metal or alloy layer, Coating or impregnation functions biologically [e.g., insect repellent, antiseptic, insecticide, bactericide, etc. Phenotype of exogenous microparticle-containing pigment cells of the human Peyers patch in inflamed and normal ileum.

The presence of these reflectant particles in blood roughly mirrored the levels of total titanium by ICP-MS, providing good evidence for the latter being a measure of whole particle (titanium dioxide) absorption. Indeed, there was a positive correlation between reflectance grades and total Ti levels (Fig. Exposure to persistent engineered nano and micro particles via the oral route is well established. 3, Absorption of TiO2 particles into the blood stream. With histological studies in rodents he developed the concept of persorption whereby holes in the tips of intestinal villi allow the ingress of particles [6, 7].

In one embodiment of the invention, the marker substance(s) is/are added prior to calcining in the framework of the sulphate process.

(i.e.

Marking during surface treatment is preferred for reasons of process engineering. b- Total Ti levels (ppb) measured by ICP-MS in the same blood samples as above with two further subjects (total seven). Secondly, it provides further evidence to agree with Bockmanns observations that, in humans, a bimodal pattern of particle uptake occurs: it starts early (i.e. If so, this pattern may be explained by some absorption in the proximal small intestine (duodenum/jejunum) [1, 7] with later Peyers patch uptake in the more distal small intestine (ileum) [1]. between 010 h). The marker substance can also be used as the sole surface treatment component. Immediately following this, subjects ingested two capsules each containing 50mg of pharmaceutical/food grade TiO2 (total 100mg) with 250ml water - one capsule was taken immediately following the other. There is consequently great interest in methods that can be used for unequivocally and reliably distinguishing original products from fake products. Using large micron-sized biological particles (such as starch and pollen), Volkeimer has convincingly shown their appearance in the blood stream following ingestion by humans. in vehicle refinish paints or other high-quality coatings, the pigment manufacturer can identify its own and third-party pigments with the help of the pigment marking. government site. 23, 2006.

The pigment is subsequently separated by filtration, freed of water-soluble salts by washing, dried and steam-milled. In another method, inks that are transparent in visible light are, for example, applied to the outside of documents, and their presence or absence is detected by means of ultraviolet or infrared fluorescence. metal carbonyls, GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS, TECHNICAL SUBJECTS COVERED BY FORMER USPC, TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION, Fabric [woven, knitted, or nonwoven textile or cloth, etc. scored 0; Figs. SFAB and DK were responsible for the coordination and logistics of blood samples for analysis by ICP-MS, and for the interpretation of resulting ICP-MS data. In summary, we show here that a portion of ingested pharmaceutical and food grade TiO2, to which humans are very frequently orally exposed, is directly absorbed, as particles, into the blood stream of healthy volunteers. ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TIEDEMANN, PETER;BLUMEL, SIEGFRIED;HERZOG, ROLAND;AND OTHERS;REEL/FRAME:019375/0173, Free format text:

Aqueous surface treatment customarily starts with an aqueous titanium dioxide base material suspension, which is first milled in a stirred mill and to which the solution of a corresponding water-soluble salt of the coating substance is then added, e.g. The

Additionally, the sporadic occurrence of small M-cell rich areas throughout the small intestine [22] may also provide ports of entry for particles, or the nano fraction of the ingested particles could pass through regular epithelial cells to underlying dendritic cells, as recently described [23].

2 and and3a).3a). The method is used to verify authentic product, to identify product forgeries (product piracy), to track distribution channels, or to identify the pigment used in order to counter unjustified complaints. Further work will need to confirm the proposed proximal intestinal uptake of particles, in humans, and the underlying mechanisms, but a preference for penetration by the nano-sized fraction should not be ruled out as this is seen in rodents [18, 19]. The site is secure. As a result of appropriate pH value control, a hydrated oxide or a phosphate is deposited on the titanium dioxide surface.

due to interactions with other raw material components.

the subjects only ingested TiO2 particles and the lunch provided had no particulate additives).

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Visualisation of TiO2 particles by dark field microscopy could only be carried out in five out of seven subjects due to clotting of blood in two subjects. Examples of particle-positive signals are indicated by the white arrows. Blood samples were heparinised and analysed as described below. Particularly suitable as marker substances are the lanthanides, yttrium, zinc, molybdenum, tungsten, germanium, tin and scandium. In addition, manufacturers of high-quality, branded garments can identify fakes by using fibre fabrics delustered with correspondingly marked TiO2 pigments in their products.

The seemingly early absorption and late peak of uptake point towards two distinct periods and perhaps routes of uptake: one early in the proximal small intestine and one late in the distal small intestine. Fabricius AL, Duester L, Meermann B, Ternes TA.

Similarly, it is desirable that no negative effects on the properties of the end product occur, e.g. visible by 2h following ingestion) but peaks later (i.e. Particularly suitable as marker substances are the rare-earth metals (lanthanides), yttrium, zinc, molybdenum, tungsten, germanium, tin and scandium. One such method for marking titanium dioxide pigment particles and for verifying marked titanium dioxide pigment particles includes the steps of: using a quantity of at least one marker substance during production of the titanium dioxide particles, wherein the marker substance is detectable in a product containing the titanium dioxide particles; recording information about the marker substance; testing a product to determine whether it contains the marker substance; and comparing the results of the test to the recorded information to determine whether the product contains the marker that was used during the production of the titanium dioxide particles. JJP and MCL developed the overall hypothesis and specific study design and, with LCP, were responsible for data interpretation. Total Ti concentrations were determined by High-Resolution ICP-MS at the Department of Physical and Analytical Chemistry, University of Oviedo, Spain, using an Element 2 (Thermo Fisher Scientific, Waltham, MA, USA) working at medium resolution (RS=4000) to analyse the isotope of 47Ti [15, 16]. Further quantification work of titanium dioxide absorption at different doses, and translation to particle numbers and sizes is now needed.

Indeed, Powell and colleagues have estimated that adult humans may absorb 1012 TiO2 particles/person/day [25]. What are intestinal pigment cells? Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. The invention is explained in detail on the basis of the example below, without this in any way restricting the invention. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). TiO2). Peyers patches are intestinal lymphoid follicles lined with specialised microfold (M) cells that specifically and avidly capture small particles. will also be available for a limited time. It is desirable that the marker substances not contain any colouring elements. ), are optimised for the respective application. Bockmann J, Lahl H, Eckert T, Unterhalt B. said at least one marker substance is selected from the group comprising: the lanthanides; yttrium; zinc; molybdenum; tungsten; germanium; tin; and scandium.

One possibility consists in marking the original products. The markings on the products are usually not detectable without special analytical methods. It is likewise possible to add the marker substance during steam milling or during drying.

At 9.00am, a peripheral venous cannula was inserted and a 5ml baseline blood sample taken. Volkheimer G. Persorption of microparticles. Individual production batches can be distinguished from each other in this way.

6h following ingestion). c- Correlation between reflectance grades and total Ti levels in blood for the five complete subjects only.

The impact of the additives on the physico-chemical behaviour, and thus the utility of the titanium dioxide pigment in its customary fields of application (paints and coatings, plastics, fibres, paper, etc.) Received 2015 Jan 31; Accepted 2015 Aug 24. VT developed the techniques for the semi-quantitation of TiO2 in blood smears. and, further, to confirm that the increased levels of Ti observed in blood are due to whole particle uptake into the circulation. The .gov means its official.

The route of putative proximal absorption is less clear. Blood samples were collected from 0.5 to 10h post ingestion and analysed for the presence of reflectant bodies (particles) by dark field microscopy, and for total titanium by inductively coupled plasma mass spectrometry (ICP-MS). A dense SiO2 coating, for example, leads to improved photostability of the TiO2 pigment. Owner name: Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue. First, it confirms that persistent particles (i.e. Subjects were asked not to consume any dairy products from lunchtime the day before the test.

However, there is much less evidence in man. Tea and coffee with milk and/or sugar were allowed as desired from 11am onwards. The authors also wish to thank St Thomas Hospital Pharmacy for the manufacture of TiO2 capsules, Maria Montes-Bayn and colleagues from the Department of Physical and Analytical Chemistry, University of Oviedo for the analyses of Titanium by ICP-MS and the statistical team at MRC-HNR for guidance in statistical analyses.

Lomer MC, Hutchinson C, Volkert S, Greenfield SM, Catterall A, Thompson RP, et al. sharing sensitive information, make sure youre on a federal Oral exposure to non-biological nano- and micro- particles from the diet, environment, and man-made health and hygiene products, is now well established [1]. LCP with JJP wrote the paper. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration.

In another application, a fluorescent dye is added to the plastic of Compact Discs for marking.

Characterization of titanium dioxide nanoparticles in food products: analytical methods to define nanoparticles. using a quantity of at least one marker substance during production of the titanium dioxide particles, wherein the marker substance is detectable in a product containing the titanium dioxide particles; recording information about the marker substance; testing a product to determine whether it contains the marker substance; and comparing the results of the test to the recorded information to determine whether the product contains the marker that was used during the production of the titanium dioxide particles.

is likewise known. To date, only Bockmann et al. Shepherd NA, Crocker PR, Smith AP, Levison DA. The invention encompasses the use of both one marker substance and several marker substances in pigment production. Prepare a zinc amalgam column in a 25-cm Jones reductor tube, placing a pledget of glass wool in the bottom of the tube, and filling the constricted portion of the tube with zinc amalgam prepared as follows. Reflectance grades, rather than absolute numbers, were used for rapid data acquisition and because of the semi-quantitative nature of detection.

These substances can either be subsequently applied to the products externally, or added during production.

3c, p=0.0058 and r=0.5803). National Library of Medicine Exposure to titanium dioxide is widespread via the oral route, but only one study has provided indirect evidence (total titanium analyses) of absorption into the blood stream in humans. It is preferable that the marker substance be bound so firmly to the TiO2 surface that it is not detached by washing or other subsequent processing steps, and that it be uniformly distributed in the pigment volume.

The invention involves the addition of a marker substance, which can be used to identify the product, to the titanium dioxide pigment during the manufacturing of the product. Accessibility RPHT provided advice and support in project design and implementation.

As the pigment is usually only present in the end product in low concentrations of a few percent, it is in most cases necessary to increase the concentration of the sample of the end product to be analysed in terms of TiO.

Quantitative measurements are now merited to estimate real human exposures. as marking agent in polymeric films and articles for forgery-proof product identification, comprises organic optical brightener, which is homogeneously embedded in microspherical inorganic oxide, Composition for preventing counterfeit and method for discriminating using the same, Information on status: application discontinuation. Positive signals were assumed to be TiO2 particles since no other sources of particles were provided (i.e. Learn more

http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, Inductively coupled plasma-mass spectrometry. The method of the invention allows for marking titanium dioxide pigment particles, characterised in that a quantity of at least one marker substance is used during production of the titanium dioxide particles, where the marker substance is detectable in a product containing the titanium dioxide particles. It is therefore desirable that the marker substances used in the present invention do not alter the properties of the titanium dioxide pigment optimised for the intended field of application, but can nevertheless be detected in the end product with the help of suitable methods. Brun E, Barreau F, Veronesi G, Fayard B, Sorieul S, Chaneac C, et al. HHS Vulnerability Disclosure, Help

If the pigment is coated with roughly 100 ppm to 1,000 ppm marker substance, the latter is contained in the fibre in a concentration of 0.3 ppm to 10 ppm. The present invention also includes a method involving testing a product to determine whether it contains the titanium dioxide pigment particles produced by the method of this invention.




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