Probabilistic risk assessment of emerging materials: case study of titanium dioxide nanoparticles

The development and use of emerging technologies such as nanomaterials can provide both benefits and risks to society. Emerging materials may promise to bring many technological advantages but may not be well characterized in terms of their production volumes, magnitude of emissions, behaviour in the environment and effects on living organisms. This uncertainty can present challenges to scientists developing these materials and persons responsible for defining and measuring their adverse impacts. Human health risk assessment is a method of identifying the intrinsic hazard of and quantifying the dose–response relationship and exposure to a chemical, to finally determine the estimation of risk. Commonly applied deterministic approaches may not sufficiently estimate and communicate the likelihood of risks from emerging technologies whose uncertainty is large. Probabilistic approaches allow for parameters in the risk assessment process to be defined by distributions instead of single deterministic values whose uncertainty could undermine the value of the assessment. A probabilistic approach was applied to the dose–response and exposure assessment of a case study involving the production of nanoparticles of titanium dioxide in seven different exposure scenarios. Only one exposure scenario showed a statistically significant level of risk. In the latter case, this involved dumping high volumes of nano-TiO₂ powders into an open vessel with no personal protection equipment. The probabilistic approach not only provided the likelihood of but also the major contributing factors to the estimated risk (e.g. emission potential).     

Risk assessment of titanium dioxide nanoparticles via oral exposure,including toxicokinetic considerations

Titanium dioxide white pigment consists of particles of various sizes, from which a fraction is in the nano range (<100?nm). It is applied in food as additive E 171 as well as in other products, such as food supplements and toothpaste. Here, we assessed whether a human health risk can be expected from oral ingestion of these titanium dioxide nanoparticles (TiO₂ NPs), based on currently available information. Human health risks were assessed using two different approaches: Approach 1, based on intake, i.e. external doses, and Approach 2, based on internal organ concentrations using a kinetic model in order to account for accumulation over time (the preferred approach). Results showed that with Approach 1, a human health risk is not expected for effects in liver and spleen, but a human health risk cannot be excluded for effects on the ovaries. When based on organ concentrations by including the toxicokinetics of TiO₂ NPs (Approach 2), a potential risk for liver, ovaries and testes is found. This difference between the two approaches shows the importance of including toxicokinetic information. The currently estimated risk can be influenced by factors such as absorption, form of TiO₂, particle fraction, particle size and physico-chemical properties in relation to toxicity, among others. Analysis of actual particle concentrations in human organs, as well as organ concentrations and effects in liver and the reproductive system after chronic exposure to well-characterized TiO₂ (NPs) in animals are recommended to refine this assessment.     

Long-term exposure of A549 cells to titanium dioxide nanoparticles induces DNA damage and sensitizes cells towards genotoxic agents

Titanium dioxide nanoparticles (TiO₂-NPs) are one of the most produced NPs in the world. Their toxicity has been studied for a decade using acute exposure scenarios, i.e. high exposure concentrations and short exposure times. In the present study, we evaluated their genotoxic impact using long-term and low concentration exposure conditions. A549 alveolar epithelial cells were continuously exposed to 1–50?μg/mL TiO₂-NPs, 86% anatase/14% rutile, 24?±?6?nm average primary diameter, for up to two months. Their cytotoxicity, oxidative potential and intracellular accumulation were evaluated using MTT assay and reactive oxygen species measurement, transmission electron microscopy observation, micro-particle-induced X-ray emission and inductively-coupled plasma mass spectroscopy. Genotoxic impact was assessed using alkaline and Fpg-modified comet assay, immunostaining of 53BP1 foci and the cytokinesis-blocked micronucleus assay. Finally, we evaluated the impact of a subsequent exposure of these cells to the alkylating agent methyl methanesulfonate. We demonstrate that long-term exposure to TiO₂-NPs does not affect cell viability but causes DNA damage, particularly oxidative damage to DNA and increased 53BP1 foci counts, correlated with increased intracellular accumulation of NPs. In addition, exposure over 2 months causes cellular responses suggestive of adaptation, characterized by decreased proliferation rate and stabilization of TiO₂-NP intracellular accumulation, as well as sensitization to MMS. Taken together, these data underline the genotoxic impact and sensitization effect of long-term exposure of lung alveolar epithelial cells to low levels of TiO₂-NPs.     

Oral,short-term exposure to titanium dioxide nanoparticles in Sprague-Dawley rat: focus on reproductive and endocrine systems and spleen

The study explored possible reproductive and endocrine effects of short-term (5 days) oral exposure to anatase TiO₂ nanoparticles (0, 1, 2 mg/kg body weight per day) in rat. Nanoparticles were characterised by scanning electron microscopy (SEM) and transmission electron microscopy, and their presence in spleen, a target organ for bioaccumulation, was investigated by single-particle inductively coupled plasma mass spectrometry and SEM/energy-dispersive X-ray. Analyses included serum hormone levels (testosterone, 17-β-estradiol and triiodothyronine) and histopathology of thyroid, adrenals, ovary, uterus, testis and spleen. Increased total Ti tissue levels were found in spleen and ovaries. Sex-related histological alterations were observed at both dose levels in thyroid, adrenal medulla, adrenal cortex (females) and ovarian granulosa, without general toxicity. Altered thyroid function was indicated by reduced T3 (males). Testosterone levels increased in high-dose males and decreased in females. In the spleen of treated animals TiO₂ aggregates and increased white pulp (high-dose females) were detected, even though Ti tissue levels remained low reflecting the low doses and the short exposure time. Our findings prompt to comprehensively assess endocrine and reproductive effects in the safety evaluation of nanomaterials.     

Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles

Data generated using standardized testing protocols for toxicity studies generally provide reproducible and reliable results for establishing safe levels and formulating risk assessments. The findings of three OECD guideline-type oral toxicity studies of different duration in rats are summarized in this publication; each study evaluated different titanium dioxide (TiO₂) particles of varying sizes and surface coatings. Moreover, each study finding demonstrated an absence of any TiO₂ -related hazards. To briefly summarize the findings: 1) In a subchronic 90-day study (OECD TG 408), groups of young adult male and female rats were dosed with rutile-type, surface-coated pigment-grade TiO₂ test particles (d₅₀ = 145 nm − 21% nanoparticles by particle number criteria) by oral gavage for 90 days. The no-adverse-effect level (NOAEL) for both male and female rats in this study was 1000 mg/kg bw/day, the highest dose tested. The NOAEL was determined based on a lack of TiO₂ particle-related adverse effects on any in-life, clinical pathology, or anatomic/microscopic pathology parameters; 2) In a 28-day repeated-dose oral toxicity study (OECD TG 407), groups of young adult male rats were administered daily doses of two rutile-type, uncoated, pigment-grade TiO₂ test particles (d₅₀ = 173 nm by number) by daily oral gavage at a dose of 24,000 mg/kg bw/day. There were no adverse effects measured during or following the end of the exposure period; and the NOAEL was determined to be 24,000 mg/kg bw/day; 3) In an acute oral toxicity study (OECD TG 425), female rats were administered a single oral exposure of surface-treated rutile/anatase nanoscale TiO₂ particles (d₅₀ = 73 nm by number) with doses up to 5000 mg/kg and evaluated over a 14-day post-exposure period. Under the conditions of this study, the oral LD₅₀ for the test substance was >5000 mg/kg bw. In summary, the results from these three toxicity studies – each with different TiO₂ particulate-types, demonstrated an absence of adverse toxicological effects. Apart from reporting the findings of these three studies, this publication also focuses on additional critical issues associated with particle and nanotoxicology studies. First, describing the detailed methodology requirements and rigor upon which the standardized OECD 408 guideline subchronic oral toxicity studies are conducted. Moreover, an attempt is made to reconcile the complex issue of particle size distribution as it relates to measurements of nanoscale and pigment-grade TiO₂ particles. Clearly this has been a confusing issue and often misrepresented in the media and the scientific literature. It is clear that the particle-size distribution for pigment-grade TiO₂, contains a small (“tail”) component of nanoscale particles (i.e., 21% by particle number and <1% by weight in the test material used in the 90-day study). However, this robust particle characterization finding should not be confused with mislabeling the test materials as exclusively in the nanoscale range. Moreover, based upon the findings presented herein, there appears to be no significant oral toxicity impact contributed by the nanoscale component of the TiO₂ Test Material sample in the 90-day study. Finally, it seems reasonable to conclude that the study findings should be considered for read-across purposes to food-grade TiO₂ particles (e.g., E171), as the physicochemical characteristics are quite similar.     

An in vivo study of nanorod,nanosphere, and nanowire forms of titanium dioxide using Drosophila melanogaster: toxicity,cellular uptake,oxidative stress,and DNA damage

ABSTRACT

The biological impact of nanomaterials (NMs) is determined by several factors such as size and shape, which need to be taken into consideration in any type of analysis. While investigators often prefer to conduct in vitro studies for detection of any possible adverse effects of NMs, in vivo approaches yield more relevant data for risk assessment. For this reason, Drosophila melanogaster was selected as a suitable in vivo model to characterize the potential risks associated with exposure nanorods (NRs), nanospheres (NSs), nanowires (NWs) forms of titanium dioxide (TiO₂), and their microparticulated (or bulk) form, as TiO₂. Third instar larvae (72 hr old larvae) were fed with TiO₂ (NRs, NSs, or NWs) and TiO₂ at concentrations ranging from 0.01 to 10 mM. Viability (toxicity), internalization (cellular uptake), intracellular reactive oxygen species (ROS) production, and genotoxicity (Comet assay) were the end-points evaluated in hemocyte D. melanogaster larvae. Significant intracellular oxidative stress and genotoxicity were noted at the highest exposure concentration (10 mM) of TiO₂ (NRs, NSs, or NWs), as determined by the Comet assay and ROS analysis, respectively. A concentration–effect relationship was observed in hemocytes exposed to the NMs. Data demonstrated that selected forms of TiO₂.-induced genotoxicity in D. melanogaster larvae hemocytes indicating this organism is susceptible for use as a model to examine in vivo NMs-mediated effects.     

Tissue distribution and excretion of intravenously administered titanium dioxide nanoparticles

As the biosafety of nanotechnology becomes a growing concern, the in vivo nanotoxicity of nanoparticles (NPs) has been drawn an increasing attention. Titanium dioxide nanoparticles (TiO₂-NPs) have been developed for versatile use, but the pharmacokinetics of intravenously administered TiO₂-NPs have not been investigated extensively. In the present study, the rutile-type TiO₂-NPs with a size about 20 nm were labeled with CF680 and ¹²⁵I. The labeled TiO₂-NPs were injected in mice or rats with the concentration of 1 mg/ml and the dose of 10 mg/kg body weight and their tissue distribution and excretion were investigated by using ex vivo fluorescent imaging, γ-counter and TEM. The results indicated that the TiO₂-NPs mainly accumulated in liver and spleen and could be retained for over 30 days in these tissues due to the phagocytosis by macrophages. The excretion assay found that the excretory rate of TiO₂-NPs through urine was higher than that of feces, indicating that renal excretion was the main excretion pathway of TiO₂-NPs. Overall results of the present study provided important information on distribution and excretion of TiO₂-NPs in vivo, which would greatly promote the pharmacokinetics and in vivo nanotoxicity research of TiO₂-NPs.     

Metabolomics reveals the perturbations in the metabolome of Caenorhabditis elegans exposed to titanium dioxide nanoparticles

Abstract

The increasing use of nanotechnology in our daily life can have many unintended effects and pose adverse impact on human health, environment and ecosystems. Wider application of engineered nanoparticles, especially TiO₂ nanoparticles (TiO₂ NP) necessitates the understanding of toxicity and mechanism of action. Metabolomics provides a unique opportunity to find out biomarkers of nanoparticles exposure, which leads to the identification of cellular pathways and their biological mechanisms. Gas chromatography mass spectrometry (GC–MS)-based metabolomics approach was used in the present study to understand the toxicity of sub-lethal concentrations (7.7 and 38.5?µg/ml) of TiO₂ NP (<25?nm) in well-known, soil nematode Caenorhabditis elegans (C. elegans). Multivariate pattern recognition analysis reflected the perturbations in the metabolism (amino acids, organic acids, sugars) of C. elegans on exposure to TiO₂ NP. The biological pathways affected due to the exposure of TiO₂ NP were identified, among them mainly affected pathways are tricarboxylic acid (TCA) cycle, arachidonic acid metabolism and glyoxalate dicarobxylate metabolism. The manifestation of differential metabolic profile in organism exposed to TiO₂ (NP or bulk particle) was witnessed as an effect on reproduction. The present study demonstrates that metabolomics can be employed as a tool to understand the potential toxicity of nanoparticles in terms of organism–environment interactions as well as in assessing the organism function at the molecular level.     

Risk assessment strategies for nanoscale and fine-sized titanium dioxide particles: Recognizing hazard and exposure issues

The basic tenets for assessing health risks posed by nanoparticles (NP) requires documentation of hazards and the corresponding exposures that may occur. Accordingly, this review describes the range and types of potential human exposures that may result from interactions with titanium dioxide (TiO₂) particles or NP – either in the occupational/workplace environment, or in consumer products, including food materials and cosmetics. Each of those applications has a predominant route of exposure. Very little is known about the human impact potential from environmental exposures to NP – thus this particular issue will not be discussed further. In the workplace or occupational setting inhalation exposure predominates. Experimental toxicity studies demonstrate low hazards in particle-exposed rats. Only at chronic overload exposures do rats develop forms of lung pathology. These findings are not supported by multiple epidemiology studies in heavily-exposed TiO₂ workers which demonstrate a lack of correlation between chronic particle exposures and adverse health outcomes including lung cancer and noncancerous chronic respiratory effects. Cosmetics and sunscreens represent the major application of dermal exposures to TiO₂ particles. Experimental dermal studies indicate a lack of penetration of particles beyond the epidermis with no consequent health risks. Oral exposures to ingested TiO₂ particles in food occur via passage through the gastrointestinal tract (GIT), with studies indicating negligible uptake of particles into the bloodstream of humans or rats with subsequent excretion through the feces. In addition, standardized guideline-mandated subchronic oral toxicity studies in rats demonstrate very low toxicity effects with NOAELs of >1000 mg/kg bw/day. Additional issues which are summarized in detail in this review are: 1) Methodologies for implementing the Nano Risk Framework – a process for ensuring the responsible development of products containing nanoscale materials; and 2) Safe-handling of nanomaterials in the laboratory.     

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO₂) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO₂ particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m³ min (low dose), 826 mg/m³ min (medium dose), and 3638 mg/m³ min (high dose) of TiO₂ under the following conditions: 2.62 mg/m³ for 2 h, 1.72 mg/m³ 4 h/day for 2 days, and 3.79 mg/m³ 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.     

Lack of promoting effect of titanium dioxide particles on ultraviolet B-initiated skin carcinogenesis in rats

Titanium dioxide (TiO₂) is used in sunscreens and cosmetics as an ultraviolet light screen. TiO₂ has carcinogenic activity in the rat lung, but its effect on the skin has not been reported. We examined the promoting/carcinogenic effect of nano-size TiO₂ particles using a two-stage skin model. c-Ha-ras proto-oncogene transgenic (Hras128) rats, which are sensitive to skin carcinogenesis, and their wild-type siblings were exposed to ultraviolet B radiation on shaved back skin twice weekly for 10 weeks; then the shaved area was painted with a 100 mg/ml TiO₂ suspension twice weekly until sacrifice. All rats were killed at week 52 except for female Hras128 rats which were sacrificed at week 16 because of early mammary tumor development. Skin tumors developed in male Hras128 rats and mammary tumors developed in both sexes of Hras128 rats and in wild-type female rats, but tumor incidence was not different from controls. TiO₂ particles were detected in the upper stratum corneum but not in the underlying skin tissue layers. TiO₂ particles also did not penetrate a human epidermis model in vitro. Our data suggest that TiO₂ does not cause skin carcinogenesis, probably due to its inability to penetrate through the epidermis and reach underlying skin structures.     

Titanium dioxide nanoparticles prime a specific activation state of macrophages

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in foods, cosmetics, and medicine. Although the inhalation toxicity of TiO₂ NPs has been studied, the potential adverse effects of oral exposure of low-dose TiO₂ NPs are largely unclear. Herein, with macrophage cell lines, primary cells, and mouse models, we show that TiO₂ NPs prime macrophages into a specific activation state characterized by excessive inflammation and suppressed innate immune function. After a month of dietary exposure in mice or exposure in vitro to TiO₂ NPs (10 and 50?nm), the expressions of pro-inflammatory genes in macrophages were increased, and the expressions of anti-inflammatory genes were decreased. In addition, for macrophages exposed to TiO₂ NPs in vitro and in vivo, their chemotactic, phagocytic, and bactericidal activities were lower. This imbalance in the immune system could enhance the susceptibility to infections. In mice, after a month of dietary exposure to low doses of TiO₂ NPs, an aggravated septic shock occurred in response to lipopolysaccharide challenge, leading to elevated levels of inflammatory cytokines in serum and reduced overall survival. Moreover, TLR4-deficient mice and primary macrophages, or TLR4-independent stimuli, showed less response to TiO₂ NPs. These results demonstrate that TiO₂ NPs induce an abnormal state of macrophages characterized by excessive inflammation and suppressed innate immune function in a TLR4-dependent manner, which may suggest a potential health risk, particularly for those with additional complications, such as bacterial infections.     

ROS-mediated genotoxicity induced by titanium dioxide nanoparticles in human epidermal cells

Titanium dioxide nanoparticles (TiO₂ NPs) are among the top five NPs used in consumer products, paints and pharmaceutical preparations. Since, exposure to such nanoparticles is mainly through the skin and inhalation, the present study was conducted in the human epidermal cells (A431). A mild cytotoxic response of TiO₂ NPs was observed as evident by the MTT and NR uptake assays after 48 h of exposure. However, a statistically significant (p < 0.05) induction in the DNA damage was observed by the Fpg-modified Comet assay in cells exposed to 0.8 μg/ml TiO₂ NPs (2.20 ± 0.26 vs. control 1.24 ± 0.04) and higher concentrations for 6 h. A significant (p < 0.05) induction in micronucleus formation was also observed at the above concentration (14.67 ± 1.20 vs. control 9.33 ± 1.00). TiO₂ NPs elicited a significant (p < 0.05) reduction in glutathione (15.76%) with a concomitant increase in lipid hydroperoxide (60.51%; p < 0.05) and reactive oxygen species (ROS) generation (49.2%; p < 0.05) after 6 h exposure. Our data demonstrate that TiO₂ NPs have a mild cytotoxic potential. However, they induce ROS and oxidative stress leading to oxidative DNA damage and micronucleus formation, a probable mechanism of genotoxicity. This is perhaps the first study on human skin cells demonstrating the cytotoxic and genotoxic potential of TiO₂ NPs.     

Silicon dioxide nanoparticle exposure affects small intestine function in an in vitro model

The use of nanomaterials to enhance properties of food and improve delivery of orally administered drugs has become common, but the potential health effects of these ingested nanomaterials remain unknown. The goal of this study is to characterize the properties of silicon dioxide (SiO₂) nanoparticles (NP) that are commonly used in food and food packaging, and to investigate the effects of physiologically realistic doses of SiO₂ NP on gastrointestinal (GI) health and function. In this work, an in vitro model composed of Caco-2 and HT29-MTX co-cultures, which represent absorptive and goblet cells, was used. The model was exposed to well-characterized SiO₂ NP for acute (4?h) and chronic (5?d) time periods. SiO₂ NP exposure significantly affected iron (Fe), zinc (Zn), glucose, and lipid nutrient absorption. Brush border membrane intestinal alkaline phosphatase (IAP) activity was increased in response to nano-SiO₂. The barrier function of the intestinal epithelium, as measured by transepithelial electrical resistance, was significantly decreased in response to chronic exposure. Gene expression and oxidative stress formation analysis showed NP altered the expression levels of nutrient transport proteins, generated reactive oxygen species, and initiated pro-inflammatory signaling. SiO₂ NP exposure damaged the brush border membrane by decreasing the number of intestinal microvilli, which decreased the surface area available for nutrient absorption. SiO₂ NP exposure at physiologically relevant doses ultimately caused adverse outcomes in an in vitro model.     

Inflammatory response of mice to manufactured titanium dioxide nanoparticles: Comparison of size effects through different exposure routes

TiO₂ is a widely used manufactured nanomaterial and the opportunity for human exposure makes it necessary to study its health implications. Using murine models for inflammation, size effects of inflammatory response in instillation and acute inhalation exposures of TiO₂ nanoparticles with manufacturers’ average particles sizes of 5 and 21 nm were investigated. The properties of the primary nanoparticles, nanoparticle agglomerates aerosol and instillation solution for both sized nanoparticles were evaluated. Mice were acutely exposed in a whole-body exposure chamber or through nasal instillation and toxicity was assessed by enumeration of total and differential cells, determination of total protein, LDH activity and inflammatory cytokines in BAL fluid. Lungs were also evaluated for histopathological changes. Results show the larger TiO₂ nanoparticles were found to be moderately, but significantly, more toxic. The nanoparticles had different agglomeration states which may be a factor as important as the surface and physical characteristics of the primary nanoparticles in determining toxicity.     

Oral intake of added titanium dioxide and its nanofraction from food products,food supplements and toothpaste by the Dutch population

Titanium dioxide (TiO₂) is commonly applied to enhance the white colour and brightness of food products. TiO₂ is also used as white pigment in other products such as toothpaste. A small fraction of the pigment is known to be present as nanoparticles (NPs). Recent studies with TiO₂ NPs indicate that these particles can have toxic effects. In this paper, we aimed to estimate the oral intake of TiO₂ and its NPs from food, food supplements and toothpaste in the Dutch population aged 2 to over 70 years by combining data on food consumption and supplement intake with concentrations of Ti and TiO₂ NPs in food products and supplements. For children aged 2–6 years, additional intake via ingestion of toothpaste was estimated. The mean long-term intake to TiO₂ ranges from 0.06?mg/kg bw/day in elderly (70+), 0.17?mg/kg bw/day for 7–69-year-old people, to 0.67?mg/kg bw/day in children (2–6 year old). The estimated mean intake of TiO₂ NPs ranges from 0.19?μg/kg bw/day in elderly, 0.55?μg/kg bw/day for 7–69-year-old people, to 2.16?μg/kg bw/day in young children. Ninety-fifth percentile (P95) values are 0.74, 1.61 and 4.16?μg/kg bw/day, respectively. The products contributing most to the TiO₂ intake are toothpaste (in young children only), candy, coffee creamer, fine bakery wares and sauces. In a separate publication, the results are used to evaluate whether the presence of TiO₂ NPs in these products can pose a human health risk.     

Assessing exposure to airborne nanomaterials: Current abilities and future requirements

For over half a century, health-related aerosol exposure measurements have been characterized in terms of the mass of material present per unit volume of air. Yet recent research has challenged the applicability of this paradigm to airborne nanometer-scale particles (nanoparticles) and nanometer-structured particles (nanostructured particles). By classifying engineered nanoparticles into categories based on physical/chemical structure, and relating these categories to health impact-relevant attributes, we have explored the applicability of different physical exposure metrics to a range of particle class/attribute combinations. Using this approach, it is clear that no single method for monitoring nanoaerosol exposure will suit all nanomaterials. Rather, there will be occasions where particle number, surface area and even mass concentration measurements will play an important role in evaluating potential impact. Correspondingly, currently available techniques to measure exposure against these three metrics are reviewed. While current methods enable aerosol concentration to be evaluated against all three metrics, most techniques are inappropriate for making routine personal exposure measurements on a regular basis. We therefore explore the idea of a universal aerosol monitor, which would enable personal exposure measurements to be collected for all three metrics simultaneously, while being inexpensive enough to encourage widespread use. Such a device would provide an economical and adaptable solution to monitoring exposure to nanostructured aerosols, as both the materials and information on the potential risks they present are developed.     

Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles in human dendritic cells did not induce toxicity and changes in their functions

Nanoparticles (NPs) have been reported to penetrate into human skin through lesional skin or follicular structures. Therefore, their ability to interact with dendritic cell (DC) was investigated using DCs generated from monocytes (mono-DCs). Hybrid titanium dioxide/para-amino benzoic acid (TiO₂/PABA) NPs did not induce any cell toxicity. NPs were internalised into DCs through macropinocytosis and not by a receptor-mediated mechanism. Confocal microscopy showed that NPs were not detected in the nucleus. These data are confirmed by electronic microscopy which demonstrated that hybrid NPs were rapidly in contact with cellular membrane and localised into cytoplasmic vesicles without colocalisation with clathrin-coated vesicles. Hybrid NPs did not induce CD86 or HLA-DR overexpression or cytokine secretion (IL-8 and TNF-α) indicating no DC activation. Internalisation of hybrid NPs did not modify DC response towards sensitisers such as nickel and thimerosal or LPS used as positive controls. Moreover, hybrid NPs did not induce any oxidative stress implicated in DC activation process. After mono-DC irradiation by ultraviolet A (UVA), hybrid NP-treated cells did not produce UVA-induced reactive oxygen species (ROS) and exhibited a better cell viability compared with UVA-irradiated control cells, suggesting a protecting effect of hybrid TiO₂/PABA NPs against UVA-induced ROS.     

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

Consumer exposure to sprays containing nano-objects is a continuing concern as a potential health hazard. One potential hazard has been formulated in the overload hypothesis. It describes a volume fraction of the macrophages that is occupied by deposited nanoparticles that leads to reduced macrophage mobility. Subsequent chronic inflammation may then lead to severe health consequences including cancer. To calculate lung deposition of spherical particles, the Multiple-Path Particle Dosimetry (MPPD) model (ARA, Albuquerque, NM) provides different kinds of lung models and age settings. Using the MPPD v 2.11 software, we modeled several consumer-related exposure scenarios. Different body orientations and age groups were investigated. Moreover, a number of materials representing different densities were used, and the exposure calculated using MPPD is compared to the hazard derived from the overload hypothesis. Conditions leading to macrophage overload were found for exposures to high particle doses for prolonged times and repeated exposure. Such conditions are unlikely in the context of regular consumer exposure. The overload hypothesis assumes the particles to be inert and biopersistent, a condition that currently lacks a clear regulatory definition and is valid only for a few selected materials. Furthermore, because of material-specific effects and the possibility of surface adsorption of hazardous chemicals, nano-objects in propellant sprays remain of concern for consumer health.     

Acute and chronic toxicity of nano-scale TiO2 particles to freshwater fish,cladocerans, and green algae,and effects of organic and inorganic substrate on TiO2 toxicity

This research evaluated the toxicity of TiO₂ nanoparticles to freshwater aquatic organisms and the effects of organic and inorganic material on TiO₂ toxicity. The fathead minnow was much less acutely sensitive to TiO₂ (LC50 500 mg/l and higher) than Ceriodaphnia dubia and Daphnia pulex (mean LC50 values 7.6 and 9.2 mg/l, respectively). Total organic carbon levels of 1.5 mg/l decreased TiO₂ acute toxicity to C. dubia (LC50 > 100 mg/l), but kaolinite clay decreased TiO₂ toxicity to a lesser extent. In chronic toxicity tests, the green algae Pseudokirchneriella subcapitata was more sensitive to TiO₂ (IC25 1–2 mg/l) than C. dubia (IC25 9.4–26.4 mg/l) and the fathead minnow (IC25 values over 340 mg/l). Study results indicate that the specific organisms exposed and the effects of water quality parameters on TiO₂ toxicity should be considered in hazard evaluations of this nanoparticle.