Translocation of gold nanoparticles across the lung epithelial tissue barrier: Combining in vitro and in silico methods to substitute in vivo experiments

The lung epithelial tissue barrier represents the main portal for entry of inhaled nanoparticles (NPs) into the systemic circulation. Thus great efforts are currently being made to determine adverse health effects associated with inhalation of NPs. However, to date very little is known about factors that determine the pulmonary translocation of NPs and their subsequent distribution to secondary organs.Methods: A novel two-step approach to assess the biokinetics of inhaled NPs is presented. In a first step, alveolar epithelial cellular monolayers (CMLs) at the air-liquid interface (ALI) were exposed to aerosolized NPs to determine their translocation kinetics across the epithelial tissue barrier. Then, in a second step, the distribution to secondary organs was predicted with a physiologically based pharmacokinetic (PBPK) model. Monodisperse, spherical, well-characterized, negatively charged gold nanoparticles (AuNP) were used as model NPs. Furthermore, to obtain a comprehensive picture of the translocation kinetics in different species, human (A549) and mouse (MLE-12) alveolar epithelial CMLs were exposed to ionic gold and to various doses (i.e., 25, 50, 100, 150, 200 ng/cm 2 ) and sizes (i.e., 2, 7, 18, 46, 80 nm) of AuNP, and incubated post-exposure for different time periods (i.e., 0, 2, 8, 24, 48, 72 h).Results: The translocation kinetics of the AuNP across A549 and MLE-12 CMLs was similar. The translocated fraction was (1) inversely proportional to the particle size, and (2) independent of the applied dose (up to 100 ng/cm 2 ). Furthermore, supplementing the A549 CML with two immune cells, i.e., macrophages and dendritic cells, did not significantly change the amount of translocated AuNP. Comparison of the measured translocation kinetics and modeled biodistribution with in vivo data from literature showed that the combination of in vitro and in silico methods can accurately predict the in vivo biokinetics of inhaled/instilled AuNP.Conclusion: Our approach to combine in vitro and in silico methods for assessing the pulmonary translocation and biodistribution of NPs has the potential to replace short-term animal studies which aim to assess the pulmonary absorption and biodistribution of NPs, and to serve as a screening tool to identify NPs of special concern

Probabilistic modelling of prospective environmental concentrations of gold nanoparticles from medical applications as a basis for risk assessment

Background The use of gold nanoparticles (Au-NP) based medical applications is rising due to their unique physical and chemical properties. Diagnostic devices based on Au-NP are already available in the market or are in clinical trials and Au-NP based therapeutics and theranostics (combined diagnostic and treatment modality) are in the research and development phase. Currently, no information on Au-NP consumption, material flows to and concentrations in the environment are available. Therefore, we estimated prospective maximal consumption of Au-NP from medical applications in the UK and US. We then modelled the Au-NP flows post-use and predicted their environmental concentrations. Furthermore, we assessed the environment risks of Au-NP by comparing the predicted environmental concentrations (PECs) with ecological threshold (PNEC) values. Results The mean annual estimated consumption of Au-NP from medical applications is 540 kg for the UK and 2700 kg for the US. Among the modelled concentrations of Au-NP in environmental compartments, the mean annual PEC of Au-NP in sludge for both the UK and US was estimated at 124 and 145 μg kg−1, respectively. The mean PEC in surface water was estimated at 468 and 4.7 pg L−1, respectively for the UK and US. The NOEC value for the water compartment ranged from 0.12 up to 26,800 μg L−1, with most values in the range of 1000 μg L−1. Conclusion The results using the current set of data indicate that the environmental risk from Au-NP used in nanomedicine in surface waters and from agricultural use of biosolids is minimal in the near future, especially because we have used a worst-case use assessment. More Au-NP toxicity studies are needed for the soil compartment.ISSN:1477-315

The probabilistic aggregate consumer exposure model (PACEM): Validation and comparison to a lower-tier assessment for the cyclic siloxane D5

a b s t r a c t a r t i c l e i n f o Current practice of chemical risk assessment for consumer product ingredients still rarely exercises the aggregation of multi-source exposure. However, focusing on a single dominant source/pathway combination may lead to a significant underestimation of the risk for substances present in numerous consumer products, which often are used simultaneously. Moreover, in most cases complex multi-route exposure scenarios also need to be accounted for. This paper introduces and evaluates the performance of the Probabilistic Aggregate Consumer Exposure Model (PACEM) applied in the context of a tiered approach to exposure assessment for ingredients in cosmetics and personal care products (C&PCPs) using decamethylcyclopentasiloxane (D5) as a worked example. It is demonstrated that PACEM predicts a more realistic, but still conservative aggregate exposure within the Dutch adult population when compared to a deterministic point estimate obtained in a lower tier screening assessment. An overall validation of PACEM is performed by quantitatively relating and comparing its estimates to currently available human biomonitoring and environmental sampling data. Moderate (by maximum one order of magnitude) overestimation of exposure is observed due to a justified conservatism built into the model structure, resulting in the tool being suitable for risk assessment

Sequential Ordering Algorithm for Mass Integration: The Case of Direct Recycling

In the last three decades much effort has been devoted in process integration as a way to improveeconomic and environmental performance of chemical processes. Although the established frameworkshave undergone constant refinement toward formulating and solving complicated processintegration problems, less attention has been drawn to the problem of sequential applications ofmass integration. This work addresses this problem by proposing an algorithm for optimal orderingof the process sinks in direct recycling problems, which is compatible with the typical massintegration formulation. The order consists in selecting the optimal sink at a specific integrationstep given the selection of the previous steps and the remaining process sources. Such order isidentified through a succession of preemptive goal programming problems, namely of optimizationproblems characterized by more objectives at different priority levels. Indeed, the target foreach sink is obtained by maximizing the total flow recycled from the available process sources tothis sink and then minimizing the use of pure sources, starting from the purest one; the hierarchyis respected through a succession of linear optimization problems with a single objective function.While the conditional optimality of the algorithm holds always, a thorough statistical analysis includingstructured to random scenarios of process sources and process sinks shows how frequentlythe sequential ordering algorithm is outperformed with respect to the total recycledamount by a different selection of process sinks with the same cardinality. Two more case studiesproving the usefulness of ordering the process sinks are illustrated. Extensions of the algorithmare also identified to cover more aspects of the process integration framework

Exploring the Use of Molecular Docking to Identify Bioaccumulative Perfluorinated Alkyl Acids (PFAAs)

Methods to predict the bioaccumulation potential of per- and polyfluorinated alkyl substances (PFAS) are sorely needed, given the proliferation of these substances and lack of data on their properties and behavior. Here, we test whether molecular docking, a technique where interactions between proteins and ligands are simulated to predict both bound conformation and interaction affinity, can be used to predict PFAS binding strength and biological half-life. We show that an easy-to-implement docking program, Autodock Vina, can successfully redock perfluorooctanesulfonate (PFOS) to human serum albumin with deviations smaller than 2 Å. Furthermore, predicted binding strengths largely fall within one standard deviation of measured values for perfluorinated alkyl acids (PFAAs). Correlations with half-lives suggest both membrane partitioning and protein interactions are important, and that serum albumin is only one of a number of proteins controlling the fate of these chemicals in organisms. However, few data are available for validation of our approach as a broad screening tool, and available data are highly variable. We therefore call for collection of new data, particularly including proteins other than serum albumin and substances beyond perfluorooctanoic acid (PFOA) and PFOS. The methods we discuss in this work can serve as a framework for guiding such data collection

Describing the environmental fate of diuron in a tropical river catchment

The use of the herbicide diuron on sugarcane fields along the river catchments of the Great Barrier Reef (GBR) in Australia is an issue of concern due to high levels of diuron reported in the GBR lagoon, and has recently led to a restriction on the use of diuron during the 2011/12 wet season. An important question in this context is how much diuron is mobilised from the agricultural area by strong rainfall and floods in the wet season and transferred to the GBR lagoon. We have set up a multimedia chemical fate model for a tropical catchment to describe the fate of diuron within the Tully River catchment, Queensland, Australia. The model includes highly variable rainfall based on meteorological data from the Tully River catchment and a flood water compartment on top of the agricultural soil that is present during times for which floods were reported. The model is driven by diuron application data estimated for the Tully River catchment and is solved for time-dependent diuron concentrations in agricultural soil and seawater. Model results show that on average 25% of the diuron applied every year is transferred to the GBR lagoon with rainwater and flood water runoff. Diuron concentrations estimated for the seawater range from 0.1 ng/L to 12 ng/L and are in good agreement with concentrations measured in the GBR lagoon. The uncertainty of the diuron concentrations estimated for seawater is approximately a factor of two and mainly derives from uncertainty in the diuron degradation half-life in soil, properties of the soil compartment such as organic matter content, and the speed of the seawater current removing diuron dissolved in seawater from the seawater compartment of the model. (C) 2012 Elsevier B.V. All rights reserved

Online characterization of nano-aerosols released by commercial spray products using SMPS-ICPMS coupling

Nanoparticle-containing sprays are a critical class of consumer products, since human exposure may occur by inhalation of nanoparticles (NP) in the generated aerosols. In this work, the suspension and the released aerosol of six different commercially available consumer spray products were analyzed. Next to a broad spectrum of analytical methods for the characterization of the suspension, a standardized setup for the analysis of aerosol has been used. In addition, a new online coupling technique (SMPS-ICPMS) for the simultaneous analysis of particle size and elemental composition of aerosol particles has been applied. Results obtained with this new method were confirmed by other well-established techniques. Comparison of particles in the original suspensions and in the generated aerosol showed that during spraying single particles of size less than 20nm had been formed, even though in none of the suspensions particles of size less than 280nm were present (Aerosol size range scanned: 7-300nm). Both pump sprays and propellant gas sprays were analyzed and both released particles in the nm size range. Also, both water-based and organic solvent-based sprays released NP. However, a trend was observed that spraying an aqueous suspension contained in a pump spray dispenser after drying resulted in bigger agglomerates than spraying organic suspensions in propellant gas dispensers. Graphical Abstract

Polybrominated Diphenyl Ether (PBDE) Accumulation in Farmed Salmon Evaluated Using a Dynamic Sea-Cage Production Model

Food is an important source of human exposure to hazardous chemicals. Chemical concentration in a food item depends on local environmental contamination, production conditions, and, for animal-derived foods, on feed. Here, we investigate these influences on the accumulation of individual polybrominated diphenyl ether congeners (PBDEs) in farmed Atlantic salmon (<i>Salmo salar</i>). We develop a dynamic model over a full sea-cage salmon production cycle. To assess the influence of metabolic debromination on PBDE congener profiles, in vitro measurements of debromination rates in fish liver cells were extrapolated to whole-body metabolic rate constants. Model results indicate that the dominant factors governing PBDE concentration in Atlantic salmon fillet are uptake via contaminated feed and fish growth, whereas the influence of metabolic debromination is minor. PBDE concentrations in fish feed depend on several factors, including the geographic origin of fish feed ingredients, which are produced and traded globally. Human exposure to PBDE via salmon consumption is less influenced by environmental concentrations at the location of salmon farming than by environmental concentrations influencing feed components. This dependence of PBDE concentrations in salmon on the origin and composition of feed reveals the complexity of predicting contaminant concentrations in globally traded food

MOESM1 of Probabilistic modelling of prospective environmental concentrations of gold nanoparticles from medical applications as a basis for risk assessment

Additional file 1. Supporting Informatio