Exploring the utility of the Threshold of Toxicological Concern (TTC) as a screening approach for complex substances.

The Threshold of Toxicological Concern (TTC) has been applied to assess chemical safety for use, particularly in the food safety area. Although the TTC was developed for application to an individual chemical structure, more recently this concept has been suggested for the assessment of combined exposures to multiple chemicals. This study evaluated the potential for applying the TTC to a specific type of co-exposure, that of a complex substance of variable composition which contains multiple constituents, following the World Health Organization/International Programme on Chemical Safety framework for risk assessment of combined exposure to multiple chemicals. The results indicated that the TTC threshold was lower (i.e., more conservative) than regulatory thresholds derived for the same substance or even its most toxic constituent, providing assurance that the TTC could meet the requirements for a conservative screening process. This case study indicates that the TTC concept can be a useful tool to screen for potential risks from complex substances, with the consideration of additional aspects such as variability in chemical constituents and their relative proportions within the substance.

An experimental investigation of light emission produced in the process of positronium formation in matter.

The excess energy emitted during the positronium (Ps) formation in condensed matter may be released as light. Spectroscopic analysis of this light can be a new method of studying the electronic properties of materials. We report the first experimental attempt, according to our knowledge, to verify the existence of this emission process. As a result, the possibility of the emission of photons during Ps formation is within the experimental uncertainty in two different solids: an n-alkane and porous silica. However, it seems that the Ps formation on the alkane surface is not accompanied by the emission of photons with energy in the detection range of 1.6-3.8 eV. Various processes that can influence the energy of the photon emitted during the Ps formation are discussed to elucidate this issue. To aid future experiments, equations were developed to estimate the expected ratio of light emission events to annihilation events with the presence or absence of a photon during the Ps formation.

Free volume in the smectic-E phase of 4-hexyl-4' isothiocyanatobiphenyl studied by positron annihilation spectroscopy.

Positron annihilation lifetime spectroscopy has been used to study 4-hexyl-4'-isothiocyanatobiphenyl. Changes of the orthopositronium lifetime parameters with temperature have been observed for the supercooled smectic-E phase. The measurements confirm that positronium is created and annihilates in a layer of a lower electron density containing alkyl chains of molecules. The two-state bond-lattice model of glass transition explains the thermal activation of the centers where orthopositronium is created and annihilates when the glass of the smectic-E phase softens. However, the subsequent cold crystallization of the softened regions also influences the orthopositronium lifetime and intensity, which complicates the picture seen by positrons. The measurements during isothermal crystallization suggest that it progresses in two stages. The first stage can be described by the Avrami equation with the Avrami exponent close to unity, which indicates low-dimensional crystallization. Similarly to liquid n alkanes, the application of pressure is equivalent to temperature lowering with the similar equivalence relationship between pressure and temperature, which seems to confirm the structure of the smectic-E phase with sublayers containing alkyl chains in a molten state. The dependence of the orthopositronium lifetime on pressure for the smectic-E phase may be described by the bubble model where the positronium bubble is approximated with a finite square potential well with the depth of U=1.45eV.

Evaluation of Single-Chip, Real-Time Tomographic Data Processing on FPGA SoC Devices.

A novel approach to tomographic data processing has been developed and evaluated using the Jagiellonian positron emission tomography scanner as an example. We propose a system in which there is no need for powerful, local to the scanner processing facility, capable to reconstruct images on the fly. Instead, we introduce a field programmable gate array system-on-chip platform connected directly to data streams coming from the scanner, which can perform event building, filtering, coincidence search, and region-of-response reconstruction by the programmable logic and visualization by the integrated processors. The platform significantly reduces data volume converting raw data to a list-mode representation, while generating visualization on the fly.

Solid-state dynamics and single-crystal to single-crystal structural transformations in octakis(3-chloropropyl)octasilsesquioxane and octavinyloctasilsesquioxane.

Reactive octahedral silsesquioxanes of rod-like [octakis(3-chloropropyl)octasilsesquioxane - T8(CH2CH2CH2Cl)8] and spherical [octavinyloctasilsesquioxane - T8(CH[double bond, length as m-dash]CH2)8] structure can undergo reversible thermally induced phase transitions in the solid state. The phase behaviour has been studied with differential scanning calorimetry (DSC, including temperature modulated DSC), X-ray diffraction, dielectric relaxation spectroscopy (DRS), and nuclear magnetic resonance spectroscopy in the solid state (SS NMR), as well as positron annihilation lifetime spectroscopy (PALS) and polarized optical microscopy (POM). The mechanisms involving fitting the molecules into most symmetrical crystal lattices vary for species of different structure. Thermal energy can be used to expand the crystal lattice leading to thermochromism in the case of T8(CH[double bond, length as m-dash]CH2)8 or conversely to an unusual negative thermal expansion of crystals of T8(CH2CH2CH2Cl)8 that results in their self-actuation. The complex behaviour is reflected in unusual changes in the capacitance and fractional free volume of the material. These phenomena can be used for molecular design of advanced well-defined hybrid materials capable of reversible thermally induced structural transformations. The findings present a new perspective for POSS-based flexible metal-organic frameworks (MOF) of cooperative structural transformability via entropy-based translational sub-net sliding.

Using exposure bands for rapid decision making in the RISK21 tiered exposure assessment.

The ILSI Health and Environmental Sciences Institute (HESI) Risk Assessment in the Twenty-first Century (RISK21) project was initiated to address and catalyze improvements in human health risk assessment. RISK21 is a problem formulation-based conceptual roadmap and risk matrix visualization tool, facilitating transparent evaluation of both hazard and exposure components. The RISK21 roadmap is exposure-driven, that is, exposure is used as the second step (after problem formulation) to define and focus the assessment. This paper describes the exposure tiers of the RISK21 matrix and the approaches to adapt readily available information to more quickly inform exposure at a screening level. In particular, exposure look-up tables were developed from available exposure tools (European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) for worker exposure, ECETOC TRA, European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) for consumer exposure, and USEtox® for indirect exposure to humans via the environment) and were tested in a hypothetical mosquito bed netting case study. A detailed WHO risk assessment for a similar mosquito net use served as a benchmark for the performance of the RISK21 approach. The case study demonstrated that the screening methodologies provided suitable conservative exposure estimates for risk assessment. The results of this effort showed that the RISK21 approach is useful for defining future assessment efforts, focusing assessment activities and visualizing results.

Positron annihilation studies of 4-n-butyl-4'-isothiocyanato-1,1'-biphenyl.

Positron annihilation lifetime spectroscopy (PALS) measurements were performed between 93 and 293 K in order to study the supercooled smectic-E (Sm-E) phase of 4-n-butyl-4'-isothiocyanato-1,1'-biphenyl (4TCB), the ordered molecular crystal of 4TCB, and the phase transition between the Sm-E phase and the ordered molecular crystal of 4TCB. The phase transition was well reflected in the abrupt increase of the ortho-positronium (o-Ps) lifetime and intensity. The value of the o-Ps lifetime in the Sm-E liquid crystalline phase of 4TCB, i.e., 2.21 ns at room temperature, was explained by the formation of bubbles induced by Ps atoms, which are created due to a liquidlike state of the butyl chains of 4TCB molecules in the Sm-E phase. The temperature dependence of the o-Ps intensity for the supercooled Sm-E phase can be explained by thermal generation of sites where bubbles are formed; an activation energy equal to 0.30±0.02 eV was estimated. This value was compared with the activation energies of molecular motions. The o-Ps lifetime in the ordered molecular crystal was interpreted as originating from the annihilation of o-Ps confined in molecular vacancy-type imperfections in the crystal lattice. The value of the o-Ps pickoff annihilation between 1.8 and 1.9 ns is in accordance with the size of the molecular vacancy for the 4TCB crystal lattice. Its intensity is lower than 5%. The isothermal crystallization of the 4TCB Sm-E phase was observed by PALS. The low-dimensional crystal growth was concluded from the Avrami equation fitted to the time dependence of the o-Ps intensity, which resulted in an Avrami exponent equal to 1.73.

Nanostructured polymer-titanium composites and titanium oxide through polymer swelling in titania precursor.

Polymer (XAD7HP)/Ti4+ nanocomposites were prepared through the swelling of polymer in titanium (IV) ethoxide as a titanium dioxide precursor. The nanocomposite beads exhibit relatively high porosity different than the porosity of the initial polymer. Thermal treatment of composite particles up to 200 °C in vacuum causes the change of their internal structure. At higher temperature, the components of composite become more tightly packed. Calcination at 600 °C and total removal of polymer produce spherically shaped TiO2 condensed phase as determined by XRD. Thermally treated composites show the substantial change of pore dimensions within micro- and mesopores. The presence of micropores and their transformation during thermal processing was studied successfully by positron annihilation lifetime spectroscopy (PALS). The results derived from PALS experiment were compared with those obtaining from low-temperature nitrogen adsorption data.

ExpoFacts--an overview of European exposure factors data.

European exposure factor data have been collected in one centrally available, freely accessible site on the Internet: the ExpoFacts database (http://www.ktl.fi/expofacts/). The process of compiling the database required locating the exposure factor data and evaluating its general applicability and public availability. The scope of the ExpoFacts database covers 30 European countries, often each with its own approach for data generation and publication. The database includes information on food intake, time use, physiology, housing, and demographic parameters, as available. Information included in the database, as well as the challenges in collecting and compiling this information, are summarized. Data were found to be unavailable for ExpoFacts for a number of reasons: (1) data have not been collected, (2) collected data are not published, (3) the publishing format or language makes the data hard to locate and use, (4) copyright restrictions prevent presenting the data in an open access website, or (5) data exist, but are too expensive to acquire. Improving accessibility and harmonization of existing data would enhance the information base for exposure and risk assessments. In addition, the ExpoFacts project demonstrates a successful process for acquiring, storing, and sharing exposure factors data.

Vacuum removal of the template in MCM-41 silica studied by the positron annihilation method.

Positron annihilation lifetime spectra were measured for ordered silica before template (octadecyltrimethyl ammonium) removal. An intermediate lifetime component, well pronounced in the spectra, indicates the presence of structural defects in the template being the size of a surfactant molecule. At the temperature near 420 K a radical change of template structure occurs, consisting in appearance of disorder and the degradation of template; evaporation of the fragments begins. It seems that moderate heating (up to about 500 K only) in vacuum for several hours is an effective and simple method of template removal, leaving no pure carbon residue in the pore structure. The results are compared with the data from the liquid nitrogen adsorption/desorption method and elemental analysis, confirming the positron annihilation results.

A tiered approach to assessing children's exposure: a review of methods and data.

From a public health view, there are many important issues to improving children's and adolescent's health, for example, prenatal and childhood nutrition, immunizations, infectious disease control, and drug/alcohol/tobacco control. There has been increasing emphasis worldwide on protecting children from adverse health effects due to environmental factors, including chemicals. For well-studied contaminants (e.g. lead) the risks to children are reasonably known and appropriate risk management actions, in a public health context, can be undertaken. For a number of other chemicals, hazard and exposure data are less complete, and risk-based priorities are consequently less substantive. The US EPA's Voluntary Children's Chemical Evaluation Program proposal prompted additional efforts to develop and improve methods and data for assessing children's exposure. The goal is to efficiently identify the substances and conditions that present the highest potential risks to children, so that resources can be applied efficiently to assure their health improvement. The methods we illustrate use an iterative (tiered) approach for (a) screening level and (b) more detailed exposure assessments relevant to children. We also review and reference the key information sources available for such assessments and analyze the information and method's strengths and limitations.

A tiered approach for assessing children's exposure.

Recently, intense attention has been given to children's health issues, particularly in the use of consumer products. Because of this attention, researchers have been planning and initiating studies specifically aimed at developing both toxicology data and exposure data directed to improve our understanding of industrial and consumer product chemical impacts on children's health. To ensure that this research is focused on the highest priority chemicals, we present a methodology for determining and prioritizing the higher hazard chemicals and scenarios for which children could be disproportionately or highly exposed. This tiered approach includes a screening step for initial chemical selection, a hazard assessment based on no- or lowest-observed-adverse-effect levels, and a margin of exposure (MOE) calculation. The initial chemical screen focuses on the chemical presence in specific media that are special to children, such as foods children regularly eat and drink, residential or school air, products children use, and soil and dust in and around residences. Data from the literature or from models serve as the initial exposure estimate. This methodology would allow us to focus on those chemicals to which children are most exposed that are also associated with, potentially, the highest risk. Use of the MOE calculation allows for comparison among chemicals, prioritization of chemicals for evaluation and testing, and identification of significant data gaps.

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)