An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core.

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles.

Scalable liquid shear-driven fabrication of polymer nanofibers.

A simple process for batch or continuous formation of polymer nanofibers and other nanomaterials in the bulk of a sheared fluid medium is introduced. The process may be of high value to commercial nanotechnology, as it can be easily scaled up to the fabrication of staple nanofibers at rates that may exceed tens of kilograms per hour.

High-throughput models for exposure-based chemical prioritization in the ExpoCast project.

The United States Environmental Protection Agency (U.S. EPA) must characterize potential risks to human health and the environment associated with manufacture and use of thousands of chemicals. High-throughput screening (HTS) for biological activity allows the ToxCast research program to prioritize chemical inventories for potential hazard. Similar capabilities for estimating exposure potential would support rapid risk-based prioritization for chemicals with limited information; here, we propose a framework for high-throughput exposure assessment. To demonstrate application, an analysis was conducted that predicts human exposure potential for chemicals and estimates uncertainty in these predictions by comparison to biomonitoring data. We evaluated 1936 chemicals using far-field mass balance human exposure models (USEtox and RAIDAR) and an indicator for indoor and/or consumer use. These predictions were compared to exposures inferred by Bayesian analysis from urine concentrations for 82 chemicals reported in the National Health and Nutrition Examination Survey (NHANES). Joint regression on all factors provided a calibrated consensus prediction, the variance of which serves as an empirical determination of uncertainty for prioritization on absolute exposure potential. Information on use was found to be most predictive; generally, chemicals above the limit of detection in NHANES had consumer/indoor use. Coupled with hazard HTS, exposure HTS can place risk earlier in decision processes. High-priority chemicals become targets for further data collection.

Incorporating exposure information into the toxicological prioritization index decision support framework.

The Toxicological Prioritization Index (ToxPi) decision support framework was previously developed to facilitate incorporation of diverse data to prioritize chemicals based on potential hazard. This ToxPi index was demonstrated by considering results of bioprofiling related to potential for endocrine disruption. However, exposure information is required along with hazard information to prioritize chemicals for further testing. The goal of this analysis is to demonstrate the utility of the ToxPi framework for incorporating exposure information to rank chemicals and improve understanding of key exposure surrogates. The ToxPi tool was applied to common exposure surrogates (i.e., fate parameters, manufacturing volume, and occurrence measurements) and the relationship between resulting rankings and higher-tiered exposure estimates was investigated. As information more directly relevant to human exposure potential is incorporated, relative rank of chemicals changes. Binned ToxPi results are shown to be consistent with chemical priorities based on crude measures of population-level exposure for a limited set of chemicals. However, these bins are not predictive of higher tiered estimates of exposure such as those developed for pesticide registration. Although rankings based on exposure surrogates are used in a variety of contexts, analysis of the relevance of these tools is challenging. The ToxPi framework can be used to gain insight into the factors driving these rankings and aid identification of key exposure metrics. Additional exposure data is required to build confidence in exposure-based chemical prioritization.

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

The exposure data landscape for manufactured chemicals.

The U.S. Environmental Protection Agency is developing chemical screening and prioritization programs to evaluate environmental chemicals for potential risk to human health in a rapid and efficient manner. As part of these efforts, it is important to catalog available information on chemical toxicity and exposure from widely dispersed sources. The main objective of this analysis is to define important aspects of the exposure space and to catalog the available exposure information for chemicals being considered for analysis as part of the U.S. EPA ToxCast™ screening and prioritization program. Publicly available exposure data have been extracted into ACToR (Aggregated Computational Toxicology Resource), which combines information for hundreds of thousands of chemicals from >600 public sources. We use data from ACToR to assess the exposure data landscape for environmental chemicals. Of the roughly 100,000 chemicals that have at least limited toxicity information available, less than one-fifth also have exposure information - and for most of these the information is of limited utility (e.g., production volume). Readily accessible data on concentrations in exposure-related media are only available for a much smaller fraction. Among these, the largest number of chemicals is measured in water with over 1150 unique compounds, followed by 788 substances measured in soil, and 670 in air. These small numbers clearly reflect a focus of resources on those substances previously identified as possibly posing a hazard to human health. Exposure to a much broader number of chemicals will need to be measured in order to fully realize the envisioned goal of using exposure information to guide toxicity testing.

Informing selection of nanomaterial concentrations for ToxCast in vitro testing based on occupational exposure potential.

BACKGROUND: Little justification is generally provided for selection of in vitro assay testing concentrations for engineered nanomaterials (ENMs). Selection of concentration levels for hazard evaluation based on real-world exposure scenarios is desirable. OBJECTIVES: Our goal was to use estimates of lung deposition after occupational exposure to nanomaterials to recommend in vitro testing concentrations for the U.S. Environmental Protection Agency's ToxCast™ program. Here, we provide testing concentrations for carbon nanotubes (CNTs) and titanium dioxide (TiO2) and silver (Ag) nanoparticles (NPs). METHODS: We reviewed published ENM concentrations measured in air in manufacturing and R&D (research and development) laboratories to identify input levels for estimating ENM mass retained in the human lung using the multiple-path particle dosimetry (MPPD) model. Model input parameters were individually varied to estimate alveolar mass retained for different particle sizes (5-1,000 nm), aerosol concentrations (0.1 and 1 mg/m3), aspect ratios (2, 4, 10, and 167), and exposure durations (24 hr and a working lifetime). The calculated lung surface concentrations were then converted to in vitro solution concentrations. RESULTS: Modeled alveolar mass retained after 24 hr is most affected by activity level and aerosol concentration. Alveolar retention for Ag and TiO2 NPs and CNTs for a working-lifetime (45 years) exposure duration is similar to high-end concentrations (~ 30-400 µg/mL) typical of in vitro testing reported in the literature. CONCLUSIONS: Analyses performed are generally applicable for providing ENM testing concentrations for in vitro hazard screening studies, although further research is needed to improve the approach. Understanding the relationship between potential real-world exposures and in vitro test concentrations will facilitate interpretation of toxicological results.

Dielectrophoretic assembly of metallodielectric Janus particles in AC electric fields.

"Janus" particles with two hemispheres of different polarizability or charge demonstrate a multitude of interesting effects in external electric fields. We reported earlier how particles with one metallic hemisphere and one dielectric hemisphere self-propel in low-frequency alternating current (AC) electric fields. Here, we demonstrate the assembly of such Janus particles driven by AC electric fields at frequencies above 10 kHz. We investigated the relation between field-induced dielectrophoretic force, field distribution, and structure of the assemblies. The phase space for electric field intensity and frequency was explored for particle concentrations large enough to form a monolayer on a glass surface between two gold electrodes. A rich variety of metallodielectric particle structures and dynamics were uncovered, which are very different from those obtained from directed assembly of plain dielectric or plain conductive particles under the action of fields of similar frequency and intensity. The metallodielectric particles assemble into new types of chain structures, where the metallized halves of neighboring particles align into lanes along the direction of the electric field, while the dielectric halves face in alternating direction. The staggered chains may assemble in various orientations to form different types of two-dimensional metallodielectric crystals. The experimental results on the formation of staggered chains are interpreted by means of numerical simulations of the electric energy of the system. The assembly of Janus metallodielectric particles may find applications in liquid-borne microcircuits and materials with directional electric and heat transfer.

Induced-charge electrophoresis of metallodielectric particles.

The application of ac electric fields in aqueous suspensions of anisotropic particles leads to unbalanced liquid flows and nonlinear, induced-charge electrophoretic motion. We report experimental observations of the motion of Janus microparticles with one dielectric and one metal-coated hemisphere induced by uniform fields of frequency 100 Hz-10 kHz in NaCl solutions. The motion is perpendicular to the field axis and persists after particles are attracted to a glass wall. This phenomenon may find applications in microactuators, microsensors, and microfluidic devices.