Detection of titanium particles in human liver and spleen and possible health implications

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Abstract

Background

Titanium dioxide (TiO ₂) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO ₂ to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO ₂ particle consumption could not be excluded then.

Results

Here we show the first quantification of both total titanium (Ti) and TiO ₂ particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO ₂ particles. The presence of TiO ₂ in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry.

Conclusions

These results prove that TiO ₂ particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO ₂ cannot be excluded.

Electronic supplementary material

The online version of this article (10.1186/s12989-018-0251-7) contains supplementary material, which is available to authorized users.

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Titanium dioxide nanoparticles in food and personal care products.

Alex Weir, Paul Westerhoff, Lars Fabricius … (2012)

Titanium dioxide is a common additive in many food, personal care, and other consumer products used by people, which after use can enter the sewage system and, subsequently, enter the environment as treated effluent discharged to surface waters or biosolids applied to agricultural land, incinerated wastes, or landfill solids. This study quantifies the amount of titanium in common food products, derives estimates of human exposure to dietary (nano-) TiO(2), and discusses the impact of the nanoscale fraction of TiO(2) entering the environment. The foods with the highest content of TiO(2) included candies, sweets, and chewing gums. Among personal care products, toothpastes and select sunscreens contained 1% to >10% titanium by weight. While some other crèmes contained titanium, despite being colored white, most shampoos, deodorants, and shaving creams contained the lowest levels of titanium (<0.01 μg/mg). For several high-consumption pharmaceuticals, the titanium content ranged from below the instrument detection limit (0.0001 μg Ti/mg) to a high of 0.014 μg Ti/mg. Electron microscopy and stability testing of food-grade TiO(2) (E171) suggests that approximately 36% of the particles are less than 100 nm in at least one dimension and that it readily disperses in water as fairly stable colloids. However, filtration of water solubilized consumer products and personal care products indicated that less than 5% of the titanium was able to pass through 0.45 or 0.7 μm pores. Two white paints contained 110 μg Ti/mg while three sealants (i.e., prime coat paint) contained less titanium (25 to 40 μg Ti/mg). This research showed that, while many white-colored products contained titanium, it was not a prerequisite. Although several of these product classes contained low amounts of titanium, their widespread use and disposal down the drain and eventually to wastewater treatment plants (WWTPs) deserves attention. A Monte Carlo human exposure analysis to TiO(2) through foods identified children as having the highest exposures because TiO(2) content of sweets is higher than other food products and that a typical exposure for a US adult may be on the order of 1 mg Ti per kilogram body weight per day. Thus, because of the millions of tons of titanium-based white pigment used annually, testing should focus on food-grade TiO(2) (E171) rather than that adopted in many environmental health and safety tests (i.e., P25), which is used in much lower amounts in products less likely to enter the environment (e.g., catalyst supports, photocatalytic coatings).

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Titanium dioxide nanoparticles: a review of current toxicological data

Hongbo Shi, Ruth Magaye, Vincent Castranova … (2013)

Titanium dioxide (TiO2) nanoparticles (NPs) are manufactured worldwide in large quantities for use in a wide range of applications. TiO2 NPs possess different physicochemical properties compared to their fine particle (FP) analogs, which might alter their bioactivity. Most of the literature cited here has focused on the respiratory system, showing the importance of inhalation as the primary route for TiO2 NP exposure in the workplace. TiO2 NPs may translocate to systemic organs from the lung and gastrointestinal tract (GIT) although the rate of translocation appears low. There have also been studies focusing on other potential routes of human exposure. Oral exposure mainly occurs through food products containing TiO2 NP-additives. Most dermal exposure studies, whether in vivo or in vitro, report that TiO2 NPs do not penetrate the stratum corneum (SC). In the field of nanomedicine, intravenous injection can deliver TiO2 nanoparticulate carriers directly into the human body. Upon intravenous exposure, TiO2 NPs can induce pathological lesions of the liver, spleen, kidneys, and brain. We have also shown here that most of these effects may be due to the use of very high doses of TiO2 NPs. There is also an enormous lack of epidemiological data regarding TiO2 NPs in spite of its increased production and use. However, long-term inhalation studies in rats have reported lung tumors. This review summarizes the current knowledge on the toxicology of TiO2 NPs and points out areas where further information is needed.

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Industrial production quantities and uses of ten engineered nanomaterials in Europe and the world

Fabiano Piccinno, Fadri Gottschalk, Stefan Seeger … (2012)

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Author and article information

Contributors

M. B. Heringa: minne.heringa@rivm.nl

Journal

Journal ID (nlm-ta): Part Fibre Toxicol

Journal ID (iso-abbrev): Part Fibre Toxicol

Title: Particle and Fibre Toxicology

Publisher: BioMed Central (London )

ISSN (Electronic): 1743-8977

Publication date (Electronic): 11 April 2018

Publication date PMC-release: 11 April 2018

Publication date Collection: 2018

Volume: 15

Electronic Location Identifier: 15

Affiliations

[1 ]ISNI 0000 0001 2208 0118, GRID grid.31147.30, National Institute for Public Health and the Environment (RIVM), ; Bilthoven, The Netherlands

[2 ]ISNI 0000 0001 0791 5666, GRID grid.4818.5, RIKILT, , Wageningen University & Research, ; Wageningen, The Netherlands

[3 ]ISNI 0000000090126352, GRID grid.7692.a, Department of Anatomy, , University Medical Center Utrecht, ; Utrecht, The Netherlands

[4 ]TNO Earth, Life and Social Sciences, Utrecht, The Netherlands

[5 ]ISNI 0000 0001 0791 5666, GRID grid.4818.5, Present address: Division of Toxicology, , Wageningen University, ; Wageningen, The Netherlands

Article

Publisher ID: 251

DOI: 10.1186/s12989-018-0251-7

PMC ID: 5896156

PubMed ID: 29642936

SO-VID: e9a0e4c4-f062-4a5c-88d9-331db6ee3434

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 1 December 2017

Date accepted : 8 March 2018

Funding

Funded by: The Netherlands Food and Consumer Product Safety Authority (NVWA)

Funded by: FundRef http://dx.doi.org/10.13039/501100003195, Ministerie van Economische Zaken;

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ScienceOpen disciplines: Toxicology

Keywords: titanium dioxide,quantification,human liver,human spleen,tissue level,nanoparticle,risk assessment,sp-icp-hrms

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ScienceOpen disciplines: Toxicology

Keywords: titanium dioxide, quantification, human liver, human spleen, tissue level, nanoparticle, risk assessment, sp-icp-hrms

Detection of titanium particles in human liver and spleen and possible health implications

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Most cited references 33

Titanium dioxide nanoparticles in food and personal care products.

Titanium dioxide nanoparticles: a review of current toxicological data

Industrial production quantities and uses of ten engineered nanomaterials in Europe and the world

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