Development of CeO2 nanodot encrusted TiO2 nanoparticles with reduced photocatalytic activity and increased biocompatibility towards a human keratinocyte cell line.

The cytotoxic and genotoxic effects of titanium dioxide (TiO2) nanoparticles when exposed to ultraviolet (UV) radiation, particularly wavelengths between 320-400 nm, has raised concern over their safe use in health and cosmetic related products such as sunscreens. Cerium dioxide (CeO2) nanoparticles have been demonstrated to display biocompatible properties and antioxidant activity due to redox cycling of the Ce3+/Ce4+ oxidation states. In this work, CeO2/TiO2 nanocomposites were prepared through a standard precipitation method at atomic concentrations (at%) of Ce relative to Ti of 2.5, 5 and 10 at%, with the aim of reducing the photocatalytic activity of the core TiO2 nanoparticles and improve biocompatibility. The UV absorptive properties of the nanocomposite samples revealed excellent absorbance across the UV region as compared to pristine TiO2 and CeO2. Furthermore, a drastic reduction in the photocatalysed decomposition of crystal violet, when in the presence of the nanocomposite samples, under both UV and solar simulated light was observed compared to the highly photoactive pristine TiO2. An optimal CeO2 nanodot loading, displaying both high UV attenuation and low photocatalytic performance was determined at 5 at% and further in vitro biological testing revealed minimal impact on the cell viability of the human keratinocyte cell line (HaCaT) over a 24 h period with and without prior exposure to UV irradiation. In contrast, pristine TiO2 nanoparticles induced toxicity to HaCaT cells with prior UV exposure before incubation, particularly at a dosage of 100 mg L-1. Our findings demonstrate the effectiveness of CeO2 nanodots in improving biocompatibility and its potential as a coating material for active inorganic UV filters.

Y2O3 decorated TiO2 nanoparticles: Enhanced UV attenuation and suppressed photocatalytic activity with promise for cosmetic and sunscreen applications.

Nanoparticulate titanium dioxide (TiO2) is widely used in cosmetic products and sunscreens. However, primarily due to their photocatalytic activity, some TiO2 products have been shown to be cytotoxic. Thus, the aim of this study was to reduce the photoactivity and consequent cytotoxicity of TiO2nanoparticles. As such, in this work, yttrium oxide (Y2O3) was deposited onto TiO2, at 5% and 10% Y/Ti weight ratio, via a hydrothermal method. The nanocomposites produced, TiO2@Y2O3 5 and 10 wt%, were characterised to assess their physical, photochemical and toxicological properties. These materials exhibit a uniform yttria coating, enhanced UV attenuation in the 280-350 nm range and significantly reduced photoactivity compared with a pristine commercial TiO2 sample (Degussa Aeroxide® P25). Furthermore, the comparative cytotoxicity and photo-cytotoxicity of these materials to a human keratinocyte cell line (HaCaT), was assessed using a colorimetric tetrazolium salt (MTS) assay. Following 24-hour incubation with cells, both Y2O3 loadings exhibited improved biocompatibility with HaCaT cells, compared to the pristine TiO2 sample, under all subsequent test conditions. In conclusion, the results highlight the potential of these materials for use in products, applied topically, with sun protection in mind.

The Physical Work Environment and Sleep: A Latent Class Analysis.

OBJECTIVE: To investigate the relationships between the physical work environment and sleep using a person-centered approach. METHODS: A total of 542 Australian employees aged 18 to 60 years completed a survey assessing exposure to physical work environment stressors (eg, noise, poor air quality, and hazardous manual tasks), sleep timing and sleep quality, and relevant covariates. RESULTS: Latent class analysis (LCA) revealed three physical work environment classes: Infrequent exposure (51%); Occasional Exposure (31%); and Regular Exposure (18%). LCA also identified four sleep classes: Larks (24%); Typical sleep (43%); Insufficient sleep (20%); and Owls (13%). The Regular Exposure class was significantly associated with the Insufficient Sleep (odds ratio [OR] = 3.15, [1.29, 7.66]) and Owls (OR = 3.47 [1.24, 9.71]) classes. CONCLUSIONS: The person-centered approach provides important insights into how unique physical work environment experiences are linked with sleep.

Nano-sunscreens - a double-edged sword in protecting consumers from harm: viewing Australian regulatory policies through the lenses of the European Union.

Nanotechnology has the potential to bring about revolutionary changes in manufacturing products, including sunscreens. However, a knowledge gap between benefits and detriments of engineered nano-materials used in sunscreens exists, which gives rise to safety concerns. This article is concerned with the protection of consumers without impairing the embellishment of this promising technology. It is widely argued that the harm associated with nano-sunscreens may only occur under certain conditions related mainly to users skin vulnerability, which can be avoided by informed and careful use of such a product. We thus recognize the need for fostering the growth of nanotech simultaneously with preventing potential harm. We revisit the Australian sunscreens regulatory policies, which embrace a "wait and see" approach, through the lens of regulatory policies in the European Union (EU) that are influenced by a "precautionary principle." We highlight the importance of informing consumers about the sunscreen they are using and recommend that product labels should disclose the presence of nano-ingredients in line with the EU disclosure requirements. This will allow users to carefully apply the product in order to avoid any potential harm and to protect manufacturers from possible costly litigation in future. This can be achieved through a combined collaborative effort of regulators, supply chain entities, and end users.

Penicillin dust exposure and penicillin resistance among pharmaceutical workers in Tehran, Iran.

BACKGROUND: Antimicrobial resistance (AMR) adversely impacts the prevention and treatment of a wide range of infections and is considered as a serious threat to global public health. Occupational-related AMR is a neglected area of research. OBJECTIVE: To assess exposure to penicillin dust, penicillin active materials, and to report the frequency of penicillin resistance among pharmaceutical workers in Tehran, Iran. METHODS: A quasi-experimental study was conducted among workers on a penicillin production line in a pharmaceutical company (n = 60) and workers in a food producing company (n = 60). Data were collected via survey, air sampling, and throat swab. RESULTS: The mean overall concentrations of penicillin dust and penicillin active material were 6.6 and 4.3 mg/m3, respectively, in the pharmaceutical industry. Streptococcus pneumoniae (S. pneumoniae) was detected in 45% (27) individuals in the exposed group, 92.6% of which showed penicillin resistance. Resistance was significantly higher among workers in penicillin production line (p = 0.014). CONCLUSIONS: High level of AMR among workers in penicillin production line is a health risk for the workers as well as society as a whole through the spread of drug resistant micro-organisms.

Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles.

Novel engineered nanoparticles (NPs), nanomaterial (NM) products and composites, are continually emerging worldwide. Many potential benefits are expected from their commercial applications; however, these benefits should always be balanced against risks. Potential toxic effects of NM exposure have been highlighted, but, as there is a lack of understanding about potential interactions of nanomaterials (NMs) with biological systems, these side effects are often ignored. NPs are able to translocate to the bloodstream, cross body membrane barriers effectively, and affect organs and tissues at cellular and molecular levels. NPs may pass the blood-brain barrier (BBB) and gain access to the brain. The interactions of NPs with biological milieu and resulted toxic effects are significantly associated with their small size distribution, large surface area to mass ratio (SA/MR), and surface characteristics. NMs are able to cross tissue and cell membranes, enter into cellular compartments, and cause cellular injury as well as toxicity. The extremely large SA/MR of NPs is also available to undergo reactions. An increased surface area of the identical chemical will increase surface reactivity, adsorption properties, and potential toxicity. This review explores biological pathways of NPs, their toxic potential, and underlying mechanisms responsible for such toxic effects. The necessity of toxicological risk assessment to human health should be emphasised as an integral part of NM design and manufacture.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

INTRODUCTION: The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. AREAS COVERED: This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. EXPERT OPINION: Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Validation of the dynamic direct exposure method for toxicity testing of diesel exhaust in vitro.

Diesel exhaust emission is a major health concern because of the complex nature of its gaseous content (e.g., NO2, NO, CO, and CO2) and high concentration of particulate matter (PM) less than 2.5 µ m which allows for deeper penetration into the human pulmonary system upon inhalation. The aim of this research was to elucidate the potential toxic effects of diesel exhaust on a human pulmonary-based cellular system. Validation of a dynamic direct exposure method for both laboratory (230 hp Volvo truck engine) and field (Volkswagen Passat passenger car) diesel engines, at idle mode, was implemented. Human pulmonary type II epithelial cells (A549) grown on porous membranes were exposed to unmodified diesel exhaust at a low flow rate (37.5 mL/min). In parallel, diesel emission sampling was also conducted using real-time air monitoring techniques. Induced cellular effects were assessed using a range of in vitro cytotoxicity assays (MTS, ATP, and NRU). Reduction of cell viability was observed in a time-dependent manner following 30-60 mins of exposure with NRU as the most sensitive assay. The results suggest that the dynamic direct exposure method has the potential to be implemented for both laboratory- and field-based in vitro toxicity studies of diesel exhaust emissions.

Nanoparticles: a review of particle toxicology following inhalation exposure.

It is expected that the rapid expansion of nanotechnology will bring many potential benefits. However, initial investigations have demonstrated that nanomaterials may adversely affect human health and the environment. By increasing the application of nanoparticles, protection of the human respiratory system from exposure to airborne nanoparticles and ultrafine particulates has become an emerging health concern. Available research has demonstrated an association between exposure to ambient airborne particulates and ultrafine particles and various adverse heath effects including increased morbidity and mortality. Nanomaterial structures are more likely to be toxic than the same materials of conventional sized samples and can be inhaled more deeply into the lungs. While the respiratory tract is considered as the primary target organ for inhaled nanoparticles, recent research has demonstrated that extrapulmonary organs are also affected. The very small size distribution and large surface area of nanoparticles available to undergo reactions may play a significant role in nanotoxicity, yet very little is known about their interactions with biological systems. This review explores the possible underlying toxicity mechanisms of nanoparticles following inhalational exposure. Nanoparticles differ from the same conventional material at a larger scale in physical, chemical and biological characteristics; therefore it is critical to recognize the potential risk of nanoparticle exposure using appropriate toxicity test methods. Current advances and limitations of toxicity assessment methods of nanoparticles are discussed highlighting the recent improvements of in vitro screening tools for the safety evaluation of the rapidly expanding area of nanotechnology.

Inhalation toxicology.

Inhalation of gases, vapors and aerosols can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. The large number of chemicals and complex mixtures present in indoor and outdoor air coupled with the introduction of new materials such as nanoparticles and nanofibers, is an area of growing concern for human health. Animal-based assays have been used to study the toxic effects of chemicals for many years. However, even so, very little is known about the potential toxicity of the vast majority of inhaled chemicals. As well as new or refined OECD test guidelines, continuing scientific developments are needed to improve the process of safety evaluation for the vast number of chemicals and inhaled materials. Although studying the toxic effects of inhaled chemicals is more challenging, promising in vitro exposure techniques have been recently developed that offer new possibilities to test biological activities of inhaled chemicals under biphasic conditions at the air liquid interface. This chapter gives an overview of inhalation toxicology as well as focusing on the potential application of in vitro methods for toxicity testing of airborne pollutants.

Troubleshooting methods for toxicity testing of airborne chemicals in vitro.

Toxicology studies of adverse effects induced by inhaled chemicals are technically challenging, due to the requirement of highly controlled experimental conditions needed to achieve reproducible and comparable results. Therefore, many considerations must be fulfilled before adopting in vitro bioassay test systems for toxicity screening of airborne materials. However, recent methodological and technical breakthroughs of in vitro methods have the potential to fulfil the essential requirements of toxicity testing for airborne chemicals. Technology has now become available that allows cells to be cultured on permeable microporous membranes in transwell or snapwell inserts providing a very close contact between target cells and test atmospheres to study the cellular interactions caused by airborne chemical exposures without any interfering culture medium. Using a direct exposure technique at the air-liquid interface, target cells can be continuously exposed to airborne chemicals on their apical side, while being nourished from their basolateral side. Test atmospheres with different physicochemical characteristics such as gases, vapours, solid and liquid aerosols and more recently nanoaerosols, can be delivered into human target cells using static and/or direct dynamic exposure methods. Therefore, toxicological risk assessments of airborne chemicals and even complex atmospheres can be achieved using in vitro test methods in parallel with real-time air monitoring techniques to fulfil the general regulatory requirements of newly developed chemical or pharmaceutical products with the potential for inhalational exposure. In this review current toxicological methods for toxicity testing of inhaled chemicals are presented. Further, to demonstrate the potential application of in vitro methods for studying inhalation toxicity, more advanced exposure techniques developed for toxicity screening of airborne chemicals are discussed.

An integrated in vitro approach for toxicity testing of airborne contaminants.

While it is possible to establish the chemical composition of air pollutants through conventional air sampling and analytical techniques, such data do not provide direct measures of toxicity and the potential mechanisms that induce adverse effects. The aim of this study was to optimize in vitro methods for toxicity testing of airborne contaminants. An integrated approach was designed in which appropriate exposure techniques were developed. A diversified range of in vitro assays using multiple human cell systems were implemented. Direct exposure of cells to airborne contaminants was developed by culturing cells on porous membranes in conjunction with a horizontal diffusion chamber system. Concentration-response curves were generated allowing the measurement of toxicity endpoints. Regression analysis indicated a significant correlation between in vitro and published in vivo toxicity data for the majority of selected chemical contaminants. Airborne IC50 values were calculated for selected volatile organic compounds (xylene, 5350 +/- 328 ppm > toluene, 10,500 +/- 527 ppm) and gaseous contaminants (NO2, 11 +/- 3.54 ppm > SO2, 48 +/- 2.83 ppm and > NH3, 199 +/- 1.41 ppm). Results of this study indicate the significant potential of in vitro methods as an advanced technology for toxicity assessment of airborne contaminants.