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      Toxicological impact of titanium dioxide nanoparticles and food-grade titanium dioxide (E171) on human and environmental health

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          Abstract

          This review focuses on the correlation between the physico-chemical characteristics of TiO 2 nanoparticles, their passage through biological barriers, and the impact of this nanomaterial on human and environmental health.

          Abstract

          The widespread use of titanium dioxide (TiO 2) as a pigment, mostly in the form of nanoparticles (NPs), for a variety of applications, arouses increasing concerns about its possible impact on human health and aquatic and terrestrial ecosystems. Particularly relevant is the impact of ingestion of this nanomaterial from products containing food-grade TiO 2 (E171) as well as food “contaminated” by TiO 2 dispersed in the environment. In fact, TiO 2 NPs will inevitably leak into the environment and will be transported in water and soil, acting on organisms and ecosystems. TiO 2 NPs can pass through biological membranes, enter the cells and accumulate in tissues and organs, exerting toxic effects. Despite the enormous efforts in recent years to better clarify the interactions between TiO 2 NPs and the host, differences in experimental approaches and/or controversial results still make it difficult to establish a true perception of risk. To draw a more homogeneous picture of the problem, here we write a critical review of the literature-more than a taxonomic review-selecting evidence of any correlation between the physico-chemical characteristics of TiO 2 NPs, their passage through biological barriers, and the impact on human and environmental health.

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          Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles

          Günter Oberdörster, Eva Oberdörster, Jan Oberdörster (2005)
          Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
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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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                Author and article information

                Contributors
                Luisa Diomede: (View ORCID Profile)
                Journal
                Journal ID (publisher-id): ESNNA4
                Title: Environmental Science: Nano
                Abbreviated Title: Environ. Sci.: Nano
                Publisher: Royal Society of Chemistry (RSC)
                ISSN (Print): 2051-8153
                ISSN (Electronic): 2051-8161
                Publication date Created: April 14 2022
                Publication date (Electronic): 2022
                Volume: 9
                Issue: 4
                Pages: 1199-1211
                Affiliations
                [1 ]Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy
                Article
                DOI: 10.1039/D1EN00833A
                SO-VID: f3219b1c-cce8-40b8-9d7f-da57e12a7053
                Copyright © © 2022
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                http://rsc.li/journals-terms-of-use

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