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The National Institute of Standards and Technology (NIST) generates and maintains thousands of Standard Reference Materials (SRMs) to serve commerce worldwide. Many SRMs contain metrologically traceable mass fractions of known organic chemicals and are commercially available to aid the analytical chemistry community. One such material, NIST SRM 1957 Organic Contaminants in Non-Fortified Human Serum, was one of the first materials issued by NIST with measurements for per- and polyfluoroalkyl substances (PFAS) listed on the Certificate of Analysis and was commercially available in 2009. Since the release of SRM 1957, nearly 400 units have been sold to date, and over 50 publications related to PFAS measurements have included this material for multiple analytical purposes, such as a quality control material, for interlaboratory comparison, as an in-house comparison tool, for inter- and intra-day measurement accuracy, as an indicator of isomeric patterns of PFAS, and for other uses. This perspective details the ways SRM 1957 is utilized by the analytical community and how data have been reported in the literature. A discussion on accurately comparing SRM data to generated data is included. Furthermore, we conducted an in-depth investigation around additional applications for NIST SRMs, such as a matrix-matched reference material, and for the identification of targeted compounds during high-resolution mass spectrometry data collection. Ultimately, this manuscript illustratively describes the ways to utilize a NIST SRMs for chemicals of emerging concern.

Providing reliable environmental quality standards (EQSs) is a challenging issue in environmental risk assessment (ERA). These EQSs are derived from toxicity endpoints estimated from dose-response models to identify and characterize the environmental hazard of chemical compounds released by human activities. These toxicity endpoints include the classical x% effect/lethal concentrations at a specific time t (EC/LC(x, t)) and the new multiplication factors applied to environmental exposure profiles leading to x% effect reduction at a specific time t (MF(x, t), or denoted LP(x, t) by the EFSA). However, classical dose-response models used to estimate toxicity endpoints have some weaknesses, such as their dependency on observation time points, which are likely to differ between species (e.g., experiment duration). Furthermore, real-world exposure profiles are rarely constant over time, which makes the use of classical dose-response models difficult and may prevent the derivation of MF(x, t). When dealing with survival or immobility toxicity test data, these issues can be overcome with the use of the general unified threshold model of survival (GUTS), a toxicokinetic-toxicodynamic (TKTD) model that provides an explicit framework to analyse both time- and concentration-dependent data sets as well as obtain a mechanistic derivation of EC/LC(x, t) and MF(x, t) regardless of x and at any time t of interest. In ERA, the assessment of a risk is inherently built upon probability distributions, such that the next critical step is to characterize the uncertainties of toxicity endpoints and, consequently, those of EQSs. With this perspective, we investigated the use of a Bayesian framework to obtain the uncertainties from the calibration process and to propagate them to model predictions, including LC(x, t) and MF(x, t) derivations. We also explored the mathematical properties of LC(x, t) and MF(x, t) as well as the impact of different experimental designs to provide some recommendations for a robust derivation of toxicity endpoints leading to reliable EQSs: avoid computing LC(x, t) and MF(x, t) for extreme x values (0 or 100%), where uncertainty is maximal; compute MF(x, t) after a long period of time to take depuration time into account and test survival under pulses with different periods of time between them.

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade. There are new windows of susceptibility including preconception, prepuberty, a focus on the mother and not just the offspring, and a significant focus on the new field of epigenetic transgenerational inheritance. New disease focus areas have sprung up including obesity, type 2 diabetes and fatty liver disease, all with a connection to developmental exposures to EDCs. There is also a focus on the study of new EDCs, molecular mechanisms, the development of new biomarkers of exposure and disease outcomes and studies focusing on intervention and prevention studies., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Biomonitoring has been used to disclose the public health impact of contaminated sites. This study aimed at setting up good practices to apply biomonitoring targeting animal matrixes to design risk-based surveillance and exposure assessment plans. A nine-step protocol targeting farmed animals was devised and tested in three case study areas including (1) a waste dump, (2) a waste incinerator, and (3) a secondary aluminum smelter. Between 2010 and 2012, in each study area, the following 9-step best practices were applied: hazard identification, GIS project creation, risk area delimitation, control area selection, receptors (livestock) identification, farms and matrixes selection, sampling study design, on-farm secondary sources exclusion, and statistical and geostatistical analysis. Dairy farms and free-range laying hens were the primary targets: eggs from both risk and control areas and milk from risk areas were sampled and submitted for detection of selected tracking contaminants compatible with the putative sources. Comparison data (risk vs. control) of heavy metal concentrations in eggs were available only for case study 2, whereas egg comparison data of persistent organic pollutants were available for all the risk-control pairs. After taking into account potential secondary sources, no concern from metals was arisen, whereas high concentrations of persistent organic pollutants were detected in all risk areas; however, only for the aluminum smelter case study, the contamination was broad and higher in the risk area compared with the control one. The protocol has proved to be easily applicable and flexible to varying contexts and able to provide helpful data to inform risk management decisions.

Dioxins and furans are ubiquitous, anthropogenic environmental contaminants which can be found even in isolated places. Exposition to these chemicals poses several risks to humans such as thyroid dysfunction, cardiovascular diseases, and even cancer. In this review, the dioxin issue is analyzed in the light of the events that brought the World's attention to these pollutants, and the evolution of Brazilian scientific data on this matter since the citrus pulp crisis in 1998. Soil and air have been the main environmental matrices studied in Brazil. However, most of the research focuses on contaminated areas, with few or no data available on background levels. With the ratification of the Stockholm Convention in 2010, Brazil started to implement some measures to monitor the release of dioxins to the environment, such as the national inventory of sources. Still, the country lacks specific legislation stating acceptable limits for some industrial processes known to be source of dioxins emissions. Likewise, food monitoring has grown in recent years with the expansion of food groups monitored in the National Control Plan for Residues and Contaminants, but the available data do not allow affirming whether Brazilian residents are safe, as regard to exposure via food consumption. The implementation of a systemic survey such as a Total Diet Study would be a good strategy for a long-term monitoring not only for dioxins but also for other contaminants. Unfortunately, progressive cuts in science funds are holding back the scientific production in Brazil, whereas worldwide new emerging contaminants are being monitored and included in National Monitoring Plans both on food and environment matrices., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Nanotechnology is now widely used in industry as well as consumer products, such as electrical devices, cosmetics, medicine, and household appliances. In the life cycle of the nano-products, including production, use, and disposal, nanoparticles may be released to the environment. However, there is no current consensus on the best method for evaluating and characterizing nanoparticle exposure. Therefore, this chapter focuses on the nanoparticle exposure assessment methods and sampling techniques.

In 2013, the European Commission launched the Environmental Footprint Rules pilot phase. This initiative aims at setting specific rules for life cycle assessment (LCA: raw material sourcing, production, logistics, use, and disposal phase) studies within 1 product category, called product environmental footprint category rules (PEFCR), and for organizations, called organizational environmental footprint sector rules (OEFSR). Such specific rules for measuring environmental performance throughout the life cycle should facilitate the comparability between LCA studies and provide principles for communicating environmental performance, such as transparency, reliability, completeness, and clarity. Cosmetics Europe, the association representing the cosmetics industry in the European Union, completed a voluntary study into the development of PEFCR for shampoo, generally following the guidelines and methodology developed by the European Commission for its own pilot projects. The study assessed the feasibility and relevance of establishing PEFCR for shampoo. Specifically, the study defines a large number of modeling assumptions and default values relevant for shampoo (e.g., for the functional unit, the system boundaries, default transport distances, rinsing water volumes, temperature differences, life cycle inventory data sources) that can be modified as appropriate, according to the specificities of individual products, manufacturing companies, and countries. The results of the study may be used to support internal decision making (e.g., to identify "hotspots" with high environmental impact and opportunities for improvement) or to meet information requests from commercial partners, consumers, media, or authorities on product environmental characteristics. In addition, the shampoo study also highlighted many of the challenges and limitations of the current product environmental footprint (PEF) methodology, namely its complexity and resource intensiveness. It highlighted 2 areas where improvements are much needed: (1) data quality and availability, and (2) impact assessment methodologies and robustness. Many of the findings are applicable to other rinse-off cosmetic products, such as shower gels, liquid soaps, bath products, and hair conditioners. Integr Environ Assess Manag 2018;14:649-659. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2018 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Environmental risks of organic chemicals have been greatly determined by their persistence, bioaccumulation, and toxicity (PBT) and physicochemical properties. Major regulations in different countries and regions identify chemicals according to their bioconcentration factor (BCF) and octanol-water partition coefficient (Kow), which frequently displays a substantial correlation with the sediment sorption coefficient (Koc). Half-life or degradability is crucial for the persistence evaluation of chemicals. Quantitative structure activity relationship (QSAR) estimation models are indispensable for predicting environmental fate and health effects in the absence of field- or laboratory-based data. In this study, 39 chemicals of high concern were chosen for half-life testing based on total organic carbon (TOC) degradation, and two widely accepted and highly used QSAR estimation models (i.e., EPI Suite and PBT Profiler) were adopted for environmental risk evaluation. The experimental results and estimated data, as well as the two model-based results were compared, based on the water solubility, Kow, Koc, BCF and half-life. Environmental risk assessment of the selected compounds was achieved by combining experimental data and estimation models. It was concluded that both EPI Suite and PBT Profiler were fairly accurate in measuring the physicochemical properties and degradation half-lives for water, soil, and sediment. However, the half-lives between the experimental and the estimated results were still not absolutely consistent. This suggests deficiencies of the prediction models in some ways, and the necessity to combine the experimental data and predicted results for the evaluation of environmental fate and risks of pollutants., (Copyright © 2016. Published by Elsevier B.V.)

Dried blood spots (DBS) on filter paper provide a simple and convenient means of collecting, storing and shipping samples for veterinary diagnostics related to toxin exposures. This paper presents validation data on analysis of DBS for chlorinated persistent organic pollutants, specifically 4,4'-dichloro-diphenyl-trichloroethane (4,4'-DDT) and its breakdown product 4,4'-dichlorodiphenyl-dichloroethylene (4,4'-DDE), lindane and a representative polychlorinated biphenyl (PCB) congener PCB-153. Analysis was by gas chromatography with electron capture detection (GC-ECD). The method required one 12.5 mm diameter spot representing application of 50 μL of blood, and working limits of detection (LOD) for each of the compounds was 5 ppb. Data are presented on development and description of the method, assay precision, LOD and quantitation, linearity, accuracy, specificity, effects of long-term storage and ruggedness. The method was also applied to 27 avian DBS, and 4,4'-DDE was detected in the majority of samples.

Aquatic ecosystems have been suffering from contamination by multiple stressors. Traditional chemical-based risk assessment usually fails to explain the toxicity contributions from contaminants that are not regularly monitored or that have an unknown identity. Diagnosing the causes of noted adverse outcomes in the environment is of great importance in ecological risk assessment and in this regard effect-directed analysis (EDA) has been designed to fulfill this purpose. The EDA approach is now increasingly used in aquatic risk assessment owing to its specialty in achieving effect-directed nontarget analysis; however, a lack of environmental relevance makes conventional EDA less favorable. In particular, ignoring the bioavailability in EDA may cause a biased and even erroneous identification of causative toxicants in a mixture. Taking bioavailability into consideration is therefore of great importance to improve the accuracy of EDA diagnosis. The present article reviews the current status and applications of EDA practices that incorporate bioavailability. The use of biological samples is the most obvious way to include bioavailability into EDA applications, but its development is limited due to the small sample size and lack of evidence for metabolizable compounds. Bioavailability/bioaccessibility-based extraction (bioaccessibility-directed and partitioning-based extraction) and passive-dosing techniques are recommended to be used to integrate bioavailability into EDA diagnosis in abiotic samples. Lastly, the future perspectives of expanding and standardizing the use of biological samples and bioavailability-based techniques in EDA are discussed.

Publically accessible pollution databases, such as the Australian National Pollutant Inventory, contain information on chemical emissions released by industrial facility and diffuse sources. They are meant to enable public scrutiny of industrial activity, which in turn, is meant to lead to industries reducing their pollution. In Australia, however, concerns have been consistently raised that this process is not occurring. To assess whether Australia's National Pollutant Inventory is fulfilling its legislated goals, we examined the accuracy and consistency of the largest facility and diffuse source of airborne lead, a major pollutant of concern for public health. Our analysis found that the emissions estimates provided by the Inventory were not accurate and were not consistent with other sources of emissions within the Inventory, potentially distorting any user interpretation of emissions estimates provided by the National Pollutant Inventory. We conclude that for at least these important public health pollution sources, the Inventory does not fulfil its legislated goals.

Background: Biological measurements have been employed as useful biomarkers for exposure. Because of its property of reflecting toxicokinetic differences, however, within-subject variability leads to biased results in epidemiologic studies., Method: We examined the variability of lead (Pb), mercury (Hg), and cadmium (Cd) levels in blood samples from 1429 participants among 1677 elderly individuals aged over 60 years who lived in an urban area from August 2008 to April 2015., Results: The geometric means of blood Pb, Hg, Cd were 1.92μg/dL, 2.48μg/L, and 1.33μg/L, and the intra-class correlations (ICCs) were 0.81, 0.71, and 0.83, respectively. The mean values of Pb and Hg levels in this study were lower than the results from single spot samples in other national biomonitoring surveys in Korea, with the exception of Cd was higher than those in other studies. Moreover, the predicted exceedances over the guidance levels for Pb, Hg, and Cd were 1.9%, 4.2%, and 0.3%, respectively., Conclusion: Korean elderly were exposed to high levels of Pb, Hg and Cd. Especially, those who had high levels of Cd were continuously exposed to Cd during study period with the 6 collection intervals. Therefore, factors affecting environmental Cd exposure should be further studied in the future., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302-316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Normal ranges are some fraction of a reference distribution deemed to represent an expected condition, typically 95%. They are frequently used as the basis for generic criteria for monitoring programs designed to test whether a sample is outside of "normal," as in reference-condition approach studies. Normal ranges are also the basis for criteria for more classic environmental effects monitoring programs designed to detect differences in mean responses between reference and exposure areas. Limits on normal ranges are estimated with error that varies depending largely on sample size. Direct comparison of a sample or a mean to estimated limits of a normal range will, with some frequency, lead to incorrect conclusions about whether a sample or a mean is inside or outside the normal range when the sample or the mean is near the limit. Those errors can have significant costs and risk implications. This article describes tests based on noncentral distributions that are appropriate for quantifying the likelihood that samples or means are outside a normal range. These noncentral tests reverse the burden of evidence (assuming that the sample or mean is at or outside normal), and thereby encourage proponents to collect more robust sample sizes that will demonstrate that the sample or mean is not at the limits or beyond the normal range. These noncentral equivalence and interval tests can be applied to uni- and multivariate responses, and to simple (e.g., upstream vs downstream) or more complex (e.g., before vs after, or upstream vs downstream) study designs. Statistical procedures for the various tests are illustrated with benthic invertebrate community data collected as part of the Regional Aquatics Monitoring Program (RAMP) in the vicinity of oil sands operations in northern Alberta, Canada. An Excel workbook with functions and calculations to carry out the various tests is provided in the online Supplemental Data. Integr Environ Assess Manag 2017;13:188-197. © 2016 SETAC., (© 2016 SETAC.)

A method for determining a safety range for non-cancer risks is proposed, similar in concept to the range used for cancer in the management of waste sites. This safety range brings transparency to the chemical specific Reference Dose or Concentration by replacing their "order of magnitude" definitions with a scientifically-based range. EPA's multiple RfCs for trichloroethylene (TCE) were evaluated as a case study. For TCE, a multi-endpoint safety range was judged to be 3 μg/m(3) to 30 μg/m,(3) based on a review of kidney effects found in NTP (1988), thymus effects found in Keil et al. (2009) and cardiac effects found in the Johnson et al. (2003) study. This multi-endpoint safety range is derived from studies for which the appropriate averaging time corresponds to different exposure durations, and, therefore, can be applied to both long- and short-term exposures with appropriate consideration of exposure averaging times. For shorter-term exposures, averaging time should be based on the time of cardiac development in humans during fetal growth, an average of approximately 20-25 days., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

The main objective of the German Environmental Specimen Bank (ESB) is the long-term storage of environmental and human samples under stable deep-freeze conditions for future research. The ESB is unique in providing a continuous historical record of environmental and human exposure to chemicals in Germany. ESB was started parallel to the development of the first German Chemicals Legislation in the late 1970s. In 1979, the ESB test operation began. After the Chemicals Law came into force in 1982, the ESB was established as a permanent facility in 1985. With the new European Chemicals Legislation, REACH, in 2007 responsibility for the safety of commercial chemicals and risk assessment was assigned to the industry. Since then, the ESB has become even more important in verifying the self-assessment of the industry, in evaluating the effectiveness of regulations, thus ensuring the protection of humans and the environment against adverse effects caused by exposure to chemicals. These objectives are pursued by the regular monitoring of contaminations and the assessment of temporal trends. Demonstrating the necessity of deriving exposure reduction measures, ESB results serve as key information for policy-makers. Information on preventing exposure to chemicals is available to the general public and to the public health services. The ESB is thus an important monitoring instrument of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety. The Federal Environment Agency operates the ESB based on its own concepts, heads the scientific data evaluation and transfers results into the environmental policy arena and to the general public.

Undoubtedly, the most important advance in the environmental regulatory monitoring of elements of the last decade is the widespread introduction of ICP-mass spectrometry (ICP-MS) due to standards developed by the European Committee for Standardization. The versatility of ICP-MS units as a tool for the determination of major, minor and trace elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, P, Pb, Sb, Se, Sn, Ti, V and Zn) in surface water, groundwater, river sediment, topsoil, subsoil, fine particulates and atmospheric deposition is illustrated in this paper. Ranges of background concentrations for major, minor and trace elements obtained from a regional case study (Flanders, Belgium) are summarized for all of these environmental compartments and discussed in the context of a harmonized implementation of European regulatory monitoring requirements. The results were derived from monitoring programs in support of EU environmental quality directives and were based on a selection of (non-polluted) background locations. Because of the availability of ICP-MS instruments nowadays, it can be argued that the main hindrance for meeting the European environmental monitoring requirements is no longer the technical feasibility of analysis at these concentration levels, but rather (i) potential contamination during sampling and analysis, (ii) too limited implementation of quality control programs, validating the routinely applied methods (including sampling and low level verification) and (iii) lack of harmonization in reporting of the chemical environmental status between the individual member states.

Human biomonitoring (HBM) is an effective tool for assessing actual exposure to chemicals that takes into account all routes of intake. Although hair analysis is considered to be an optimal biomarker for assessing mercury exposure, the lack of harmonization as regards sampling and analytical procedures has often limited the comparison of data at national and international level. The European-funded projects COPHES and DEMOCOPHES developed and tested a harmonized European approach to Human Biomonitoring in response to the European Environment and Health Action Plan. Herein we describe the quality assurance program (QAP) for assessing mercury levels in hair samples from more than 1800 mother-child pairs recruited in 17 European countries. To ensure the comparability of the results, standard operating procedures (SOPs) for sampling and for mercury analysis were drafted and distributed to participating laboratories. Training sessions were organized for field workers and four external quality-assessment exercises (ICI/EQUAS), followed by the corresponding web conferences, were organized between March 2011 and February 2012. ICI/EQUAS used native hair samples at two mercury concentration ranges (0.20-0.71 and 0.80-1.63) per exercise. The results revealed relative standard deviations of 7.87-13.55% and 4.04-11.31% for the low and high mercury concentration ranges, respectively. A total of 16 out of 18 participating laboratories the QAP requirements and were allowed to analyze samples from the DEMOCOPHES pilot study. Web conferences after each ICI/EQUAS revealed this to be a new and effective tool for improving analytical performance and increasing capacity building. The procedure developed and tested in COPHES/DEMOCOPHES would be optimal for application on a global scale as regards implementation of the Minamata Convention on Mercury., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Epidemiologic studies evaluating associations between biomarkers of exposure to short-lived chemicals and health endpoints in humans face special challenges. Perhaps the most critical challenges are the need to determine the type and optimal number of samples, and the proper timing of specimen collection. Further, as many short-lived chemicals are ubiquitous in the environment, utmost care is required to avoid sample contamination. A separate set of challenges is associated with appropriate interpretation and reporting of results from multiple simultaneous analyses, which are becoming increasingly feasible. The Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals (BEES-C) instrument is specifically designed to evaluate the quality of epidemiologic studies that measure biomarkers of chemicals with short physiologic half-lives. The instrument provides systematic guidance for evaluating 14 different aspects of study quality divided into three broad categories: 1) biomarker selection and measurement, 2) strategy and execution of exposure assessment, and 3) general considerations of study design and reporting. We evaluated the utility of the BEES-C instrument using epidemiologic studies of exposure to bisphenol A and its association with neurodevelopmental and respiratory health indicators. Each BEES-C element was assessed with respect to needed modifications and concordance among reviewers using professional, scientific judgment. Based on this first use of the BEES-C instrument, we found that most of its elements were effective in comparing the quality of available studies, with reviews generally concordant and justifications consistent. However, we note that certain elements would be improved with slight adjustments and that one of the elements appeared redundant and should be removed., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The National Institute of Standards and Technology (NIST) has a wide range of Standard Reference Materials (SRMs) which have values assigned for legacy organic pollutants and toxic elements. Existing SRMs serve as homogenous materials that can be used for method development, method validation, and measurement for contaminants that are now of concern. NIST and multiple groups have been measuring the mass fraction of a group of emerging contaminants, polyfluorinated substances (PFASs), in a variety of SRMs. Here we report levels determined in an interlaboratory comparison of up to 23 PFASs determined in five SRMs: sediment (SRMs 1941b and 1944), house dust (SRM 2585), soil (SRM 2586), and sludge (SRM 2781). Measurements presented show an array of PFASs, with perfluorooctane sulfonate being the most frequently detected. SRMs 1941b, 1944, and 2586 had relatively low concentrations of most PFASs measured while 23 PFASs were at detectable levels in SRM 2585 and most of the PFASs measured were at detectable levels in SRM 2781. The measurements made in this study were used to add values to the Certificates of Analysis for SRMs 2585 and 2781.

In this article there are presented the current views on the technology for the assessment of the exposure to chemical pollutants with the use of the methodology of human biomonitoring and the main advantages of the latter are highlighted. There are presented main problems of the implementation of biomonitoring studies in Russia such as: beginning with the lack of the national system of the biomonitoring, and accomplishing with the inconsistency in the data within the country, the inability to assess the trend according to levels of exposure in the regional or national context. Due to the inconvenience of the Russian regulatory basis on human biomonitoring, there is persisted technological backwardness in terms of the delivery of the design, presentation and evaluation of research results, which results in the decline of the significance of biomonitoring for public health in the country. There is preserved a need for standardization and harmonization of methods and procedures of human biomonitoring (HBM) in Russia with international requirements. A serious concern is the lack of Russian programs on standardization of procedures and interlaboratcy comparison of results according to biomarkers of the exposure, the insufficient involvement of national laboratories in international programs of the comparison, the difficulties with the acquisition of standard samples of the compositionfor different environmental pollutants in biological tissues. The restraint ofthe development of HBM in the Russian Federation is caused by a complex of reasons. The most urgent task is the development of the national concept of the system with subsequent formation of technological, institutional and organizational framework of biomonitoring, as well as the improvement of Russian normative-methodical base.

Since 2007, the Canadian Health Measures Survey (CHMS) has been collecting biomonitoring data from the general Canadian population and has provided, to date, nationally representative concentrations for hundreds of environmental biomarkers in blood or urine. Biomonitoring Equivalents (BEs) have been developed as tools to help interpret biomonitoring data in a health risk context at a population level. In this paper, BEs are used to relate biomonitoring data from the CHMS (2007-2011) to existing exposure guidance values developed by Health Canada and other government agencies. Chemical-specific hazard quotients (HQs) and/or cancer risk estimates are calculated using existing BEs corresponding to environmental chemicals analyzed in the CHMS. For the majority of environmental chemicals, calculated HQ values are less than 1 indicating exposure is below published exposure guidance values. Individual biomonitoring data for two biomarkers of metal exposure (inorganic arsenic and cadmium) resulted in HQ values exceeding 1 suggesting that exposure may be above existing guidance values for a portion of the population, at least intermittently. This type of analysis may be used by researchers, risk assessors, and risk managers in prioritization efforts., (Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.)

While bioaccumulation factors (BAF) - the ratio of biota contaminant concentrations (Cbiota) to aqueous phase contaminant concentrations (Cw) - are useful in evaluating the accumulation of mercury (Hg) and other contaminants for various trophic levels in aquatic ecosystems, reduction of the underlying relationship between Cbiota and Cw to a single ratio (BAF) has inherent risks, including spurious correlation. Despite a long and rich history of remonstrations in the literature, several very recent publications evaluating Hg-related BAFs have suffered from false conclusions based on spurious correlation, and thus it seems that periodic reminders of the causes and risks of these errors are required. Herein we cite examples and explanations for unsupported conclusions from publications where authors using BAF-Cw relationships fail to recognize the underlying statistical significance (or lack thereof) of direct relationships between Cw and Cbiota. This fundamental error leads to other problems, including ascribing mechanistic significance (e.g., mechanisms related to biota contaminant uptake) to "inverse" BAF-Cw relationships that reflect nothing more than regressing the log transformed inverse of Cw (i.e., negative log) against itself (i.e., positive log transformed), and using such regression models of BAF-Cw relationships that appear significant for predictive purposes, but are misleading. Spurious correlation arising in the analysis of BAF relationships can potentially appear in more subtle forms as well, including regressing variables such as dissolved organic carbon (DOC) that are correlated with Cw. We conclude that conducting a direct analysis by examining the relationship between Cbiota and Cw (or Cbiota and other variables) rather than evaluating a ratio (BAF) is less ambiguous and subject to error, more easily interpreted, and would lead to more supportable conclusions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nanopesticides or nano plant protection products represent an emerging technological development that, in relation to pesticide use, could offer a range of benefits including increased efficacy, durability, and a reduction in the amounts of active ingredients that need to be used. A number of formulation types have been suggested including emulsions (e.g., nanoemulsions), nanocapsules (e.g., with polymers), and products containing pristine engineered nanoparticles, such as metals, metal oxides, and nanoclays. The increasing interest in the use of nanopesticides raises questions as to how to assess the environmental risk of these materials for regulatory purposes. Here, the current approaches for environmental risk assessment of pesticides are reviewed and the question of whether these approaches are fit for purpose for use on nanopesticides is addressed. Potential adaptations to existing environmental risk assessment tests and procedures for use with nanopesticides are discussed, addressing aspects such as analysis and characterization, environmental fate and exposure assessment, uptake by biota, ecotoxicity, and risk assessment of nanopesticides in aquatic and terrestrial ecosystems. Throughout, the main focus is on assessing whether the presence of the nanoformulation introduces potential differences relative to the conventional active ingredients. The proposed changes in the test methodology, research priorities, and recommendations would facilitate the development of regulatory approaches and a regulatory framework for nanopesticides.

Human exposure to chemicals may be estimated by back-calculating urinary concentrations resulting from biomonitoring studies if knowledge of the chemical's toxicokinetic properties is available. In this paper, available toxicokinetic data for back-calculating urinary concentrations into daily intake values for bisphenol A (BPA), phthalates, parabens, and triclosan (TCS) are reviewed and knowledge gaps are identified. Human data is evaluated and presented with relevant animal data. Focus is on the recovery of the administered dose, the route of administration, and differences between humans and animals. Two human toxicokinetic studies are currently used to conclude that an oral dose of BPA is recoverable in urine and that no free BPA is present in plasma in spite of several contradicting biominotoring studies. Urinary recovery of an oral dose of phthalates in humans is complicated to assess due to extensive metabolism. In animals using (14)C-marked phthalates, near-complete recovery is observed. An oral dose of (14)C-marked parabens is also almost completely recovered in animals. In both humans and animals, however, two unspecific metabolites are formed, which complicates the back-calculation of parabens in humans. The recovery of both oral and dermal TCS in humans has been studied, but due to background levels of TCS, the back-calculation is difficult to perform. In conclusion, due to limited data, reasonable estimates of daily intake values based on urinary data are often not possible to obtain. Several knowledge gaps are identified and new studies are suggested. The route of administration used in toxicokinetic studies often does not match realistic scenarios.

The need for coordinated, systematized and catalogued databases on mercury in the environment is of paramount importance as improved information can help the assessment of the effectiveness of measures established to phase out and ban mercury. Long-term monitoring sites have been established in a number of regions and countries for the measurement of mercury in ambient air and wet deposition. Long term measurements of mercury concentration in biota also produced a huge amount of information, but such initiatives are far from being within a global, systematic and interoperable approach. To address these weaknesses the on-going Global Mercury Observation System (GMOS) project ( www.gmos.eu ) established a coordinated global observation system for mercury as well it retrieved historical data ( www.gmos.eu/sdi ). To manage such large amount of information a technological infrastructure was planned. This high-performance back-end resource associated with sophisticated client applications enables data storage, computing services, telecommunications networks and all services necessary to support the activity. This paper reports the architecture definition of the GMOS Cyber(e)-Infrastructure and the services developed to support science and policy, including the United Nation Environmental Program. It finally describes new possibilities in data analysis and data management through client applications.

Global sustainability research requires an integrative research effort underpinned by digital infrastructures (systems) able to harness data and heterogeneous information across disciplines. Digital data and information sharing across systems and applications is achieved by implementing interoperability: a property of a product or system to work with other products or systems, present or future. There are at least three main interoperability challenges a digital infrastructure must address: technological, semantic, and organizational. In recent years, important international programs and initiatives are focusing on such an ambitious objective. This manuscript presents and combines the studies and the experiences carried out by three relevant projects, focusing on the heavy metal domain: Global Mercury Observation System, Global Earth Observation System of Systems (GEOSS), and INSPIRE. This research work recognized a valuable interoperability service bus (i.e., a set of standards models, interfaces, and good practices) proposed to characterize the integrative research cyber-infrastructure of the heavy metal research community. In the paper, the GEOSS common infrastructure is discussed implementing a multidisciplinary and participatory research infrastructure, introducing a possible roadmap for the heavy metal pollution research community to join GEOSS as a new Group on Earth Observation community of practice and develop a research infrastructure for carrying out integrative research in its specific domain.

Assessing ambient exposure to chemical stressors often begins with time-consuming and costly monitoring studies to establish environmental occurrence. Both human and ecological toxicology are currently challenged by the unknowns surrounding low-dose exposure/effects, compounded by the reality that exposure undoubtedly involves mixtures of multiple stressors whose identities and levels can vary over time. Long absent from the assessment process, however, is whether the full scope of the identities of the stressors is sufficiently known. The Matthew Effect (a psychosocial phenomenon sometimes informally called the "bandwagon effect" or "iceberg effect," among others) may adversely bias or corrupt the exposure assessment process. The Matthew Effect is evidenced by decisions that base the selection of stressors to target in environmental monitoring surveys on whether they have been identified in prior studies, rather than considering the possibility that additional, but previously unreported, stressors might also play important roles in an exposure scenario. The possibility that the Matthew Effect might influence the scope of environmental stressor research is explored for the first time in a comprehensive case study that examines the preponderance of "absence of data" (in contrast to positive data and "data of absence") for the environmental occurrence of a very large class of potential chemical stressors associated with ubiquitous consumer use - active pharmaceutical ingredients (APIs). Comprehensive examination of the published data for an array of several hundred of the most frequently used drugs for whether their APIs are environmental contaminants provides a prototype example to catalyze discussion among the many disciplines involved with assessing risk. The findings could help guide the selection of those APIs that might merit targeting for environmental monitoring (based on the absence of data for environmental occurrence) as well as the prescribing of those medications that might have minimal environmental impact (based on data of absence for environmental occurrence)., (© 2013. Published by Elsevier B.V. All rights reserved.)

Although the use of tissue concentrations (residues) of chemical contaminants as the dose metric to characterize chemical toxicity to aquatic organisms has been gaining acceptance over the past 20 years, tissue concentrations are less commonly used in water quality management and have yet to be formally adopted as benchmarks or environmental quality standards (EQS). This synthesis paper addresses advantages and disadvantages for the development and application of tissue-based EQS as an alternative and supplement to exposure-based EQS determined with water and sediment concentration data. Tissue-based EQS can be readily developed in parallel with conventional toxicity tests, and achieved by quantification of chemical concentrations in tissue alongside traditional concentration-response toxicity testing. Tissue-residue toxicity metrics can be used as benchmarks for screening and monitoring water and sediment quality, to derive equivalent water or sediment EQS, and for ecological risk assessments and weight of evidence approaches for assessing ecosystem impairment. Tissue-based toxicity metrics and associated EQS provide several advantages; however, there are some limitations to consider and key knowledge gaps to fill.

Evaluation of mutagenic activity--an indispensable element of the toxicological characteristics of chemicals in their hygienic regulation. In the article there is performed an analysis of the adopted in the Organization for Economic Cooperation and Development (OECD) and in Russia guidance documents on methods of assessment of the mutagenic properties of chemicals. In the OECD there are 17 manuals, each of which describes a single method, in Russia there were approved five guidance documents for specific groups of chemicals (drugs, pesticides, nanomaterials, substances normalized in the water and the air), which represent the basic and auxiliary methods of testing mutagens. Basic methods aimed to the evaluation of gene, chromosomal and genomic mutations include: assessment of gene mutations in bacteria, methods for estimating mutations in cell cultures of human and mammals in vitro, methods for inspecting mutations in somatic and germ cells of mammals in vivo. Analysis of Russian documents shows that the protocols of basic tests of assessment of the mutagenic activity are close to the protocols of the OECD. It is necessary to publish guidance documents on tests of assessment of the mutagenic activity of chemicals harmonized with the OECD documents.

The assessment of chemicals as bioaccumulative in the regulatory process makes use of the bioconcentration factor as a metric. However, this metric does not account for the dietary uptake route and therefore cannot be applied to terrestrial food chains. In recent years, the biomagnification factor (BMF) and the trophic magnification factor (TMF) have been suggested as standard metrics for bioaccumulation. For regulatory purposes, though, the BMF and the TMF also suffer from a number of shortcomings. They are not applicable to assess uptake routes other than the diet (e.g., dermal uptake, as is important for personal care products). When measured in the field, they depend largely on biological and ecological factors and less so on the chemical's properties, and they are difficult to normalize and standardize. In the present study, the authors suggest the elimination half-life (EL0.5 ) of a chemical as an alternative metric for bioaccumulation. The EL0.5 is equivalent to the depuration rate constant (k2 ) that is measured in various bioaccumulation and bioconcentration tests. This metric can be applied to air- and water-breathing animals, and it is valuable for all uptake routes. It has a number of practical advantages over the BMF and the TMF. In combination with a standard uptake scenario, the EL0.5 can also be linked directly to a BMF threshold of unity. Thus, the EL0.5 as a bioaccumulation metric overcomes the shortcomings of the BMF and the TMF while still conserving the advantages of the latter metrics., (Copyright © 2013 SETAC.)

Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Four new Standard Reference Materials (SRMs) have been developed to assist in the quality assurance of chemical contaminant measurements required for human biomonitoring studies, SRM 1953 Organic Contaminants in Non-Fortified Human Milk, SRM 1954 Organic Contaminants in Fortified Human Milk, SRM 1957 Organic Contaminants in Non-Fortified Human Serum, and SRM 1958 Organic Contaminants in Fortified Human Serum. These materials were developed as part of a collaboration between the National Institute of Standards and Technology (NIST) and the Centers for Disease Control and Prevention (CDC) with both agencies contributing data used in the certification of mass fraction values for a wide range of organic contaminants including polychlorinated biphenyl (PCB) congeners, chlorinated pesticides, polybrominated diphenyl ether (PBDE) congeners, and polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) congeners. The certified mass fractions of the organic contaminants in unfortified samples, SRM 1953 and SRM 1957, ranged from 12 ng/kg to 2200 ng/kg with the exception of 4,4'-DDE in SRM 1953 at 7400 ng/kg with expanded uncertainties generally <14 %. This agreement suggests that there were no significant biases existing among the multiple methods used for analysis.

Paired human breast milk and scalp hair samples (n=30) were obtained in 2008 from primipara and multipara mothers living in two locations in the Philippines viz., Payatas, a waste dumpsite, and Malate, a non-dumpsite. Samples were analyzed for three groups of organohalogenated compounds, such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs). PCBs were the predominantly identified compounds (median: 70 ng/g lipid wt.) in all the breast milk samples. In the human milk, CB-153 was the most dominant PCB congener (17-44% contribution to the sum PCB), closely followed by CB-138 (12-35%), CB-118 (4-12%), CB-180 (2-13%), CB-187 (3-13%), and CB-170 (1.5-10%). Levels of PBDEs (median: 3.0 ng/g lipid wt.) in human milk samples from the Philippines were similar to other Asian or European countries. BDE-47, -99, -100 and -153 were the major PBDE congeners. For HBCDs, the α-isomer was predominant followed by the γ-HBCD isomer in the both locations. PBDE levels in human milk were significantly higher in the dumpsite (3.9 ng/g lipid wt.) than in the non-dump site (2.2 ng/g lipid wt.). PBDE concentrations (including BDE-209) were significantly higher (median: 70 ng/g hair) than those of PCBs (median: 30 ng/g hair) and HBCDs (median: 1.0 ng/g hair) in all the scalp hair samples. To our knowledge, this is the first report on HBCDs in human scalp hair. PBDE congeners in scalp hair were dominated by BDE-209 and BDE-47. On a congener basis, the levels of PBDEs found in scalp hair were higher than those in Spain (children and adults) and China (general people). PCB levels found in scalp hair were higher than those in Greece, Romania and Belgium, but lower than those in China. In this study, there were no significant differences in the concentration of PCBs and HBCDs in human milk; and PCBs, HBCDs and PBDEs in human scalp hair from the two different locations. No significant correlations were observed between PCBs, PBDEs and HBCDs levels and age of mothers in this study, which may be due to the small number of samples. Furthermore, there was no correlation between milk and hair levels for more persistent compounds (PCB-153, PCB-138, or BDE-47), and thus it is worthy to follow-up in future studies along with more number of samples. This is the first report to provide measurement data for PCBs, PBDEs and HBCDs in paired milk and hair of populations in the Philippines., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The Washington State Department of Ecology annually conducts sediment quality monitoring in Puget Sound as a component of the Puget Sound Ecosystem Monitoring Program. Sediment samples are analyzed to determine the concentrations of about 170 chemical and physical variables. A Sediment Chemistry Index (SCI) was derived using the State of Washington Sediment Management Standards to account for the presence and concentrations of mixtures of toxicants. Mean Sediment Quality Standard quotients (mSQSq) were calculated as the basis for the SCI and compared to the incidence and degree of toxicity in laboratory tests and to metrics of the diversity and abundance of resident benthic assemblages in a database consisting of as many as 664 samples. These data were evaluated with co-occurrence analyses to identify "cut points" (i.e., thresholds) in the index below which the frequency and magnitude of biological effects were relatively low and above which they occurred with increasing frequency or magnitude. Iterative trials of different sets of cut points established the final cut points in mSQSq of 0.1, 0.3, and 0.5. They defined 4 ranges in chemical exposure: Minimum (<0.1), Low (0.1- < 0.3), Moderate (0.3- < 0.5), and Maximum (≥0.5). Across these 4 exposure ranges both the incidence and magnitude of toxicity in some laboratory tests increased, the abundance of most stress-sensitive benthic taxa decreased, and the abundance of most stress-tolerant taxa increased. The mSQSq cut point of 0.1 appears to be the target value for protection of benthic resources, the value below which the probability and magnitude of adverse effects either in the laboratory or the field are the lowest. The mSQSq values are rescaled from 0 to 100 to form the SCI, used by the Puget Sound Partnership and environmental managers as a Dashboard Indicator, with biologically relevant targets selected to monitor ecosystem recovery., (Copyright © 2012 SETAC.)

Standard reference materials (SRMs) are homogeneous, well-characterized materials used to validate measurements and improve the quality of analytical data. The National Institute of Standards and Technology (NIST) has a wide range of SRMs that have mass fraction values assigned for legacy pollutants. These SRMs can also serve as test materials for method development, method validation, and measurement for contaminants of emerging concern. Because inter-laboratory comparison studies have revealed substantial variability of measurements of perfluoroalkyl acids (PFAAs), future analytical measurements will benefit from determination of consensus values for PFAAs in SRMs to provide a means to demonstrate method-specific performance. To that end, NIST, in collaboration with other groups, has been measuring concentrations of PFAAs in a variety of SRMs. Here we report levels of PFAAs and perfluorooctane sulfonamide (PFOSA) determined in four biological SRMs: fish tissue (SRM 1946 Lake Superior Fish Tissue, SRM 1947 Lake Michigan Fish Tissue), bovine liver (SRM 1577c), and mussel tissue (SRM 2974a). We also report concentrations for three in-house quality-control materials: beluga whale liver, pygmy sperm whale liver, and white-sided dolphin liver. Measurements in SRMs show an array of PFAAs, with perfluorooctane sulfonate (PFOS) being the most frequently detected. Reference and information values are reported for PFAAs measured in these biological SRMs.

There are currently contradicting results in the literature about the way chloroethene (CE) concentrations from tree core sampling correlate with those from groundwater measurements. This paper addresses this issue by focusing on groundwater and tree core datasets in CE contaminated site, Czech Republic. Preliminary analyses revealed strongly and positively skewed distributions for the tree core dataset, with an intra-tree variability accounting for more than 80% of the total variability, while the spatial analyses based on variograms indicated no obvious spatial pattern for CE concentration. Using rank transformation, it is shown how the results were improved by revealing the initially hidden spatial structure for both variables when they are handled separately. However, bivariate analyses based on cross-covariance functions still failed to indicate a clear spatial correlation between groundwater and tree core measurements. Nonetheless, tree core sampling and analysis proved to be a quick and inexpensive semi-quantitative method and a useful tool., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Regarding various types of pollutant, waste management requires high attention. Environmental site selection study, prior to landfill operation, and subsequently, monitoring and maintaining of the location, are of foremost points in landfill site selection process. By means of these studies, it is possible to control the undesirable impacts caused by landfills. Study ahead aims at examination of effectiveness of a new method called Monavari 95-2 in landfill site assessment. For this purpose, two landfills Rasht and Andisheh, which are, respectively, located on humid and arid areas, were selected as case studies. Then, the results obtained from both sites were compared with each other to find out the weaknesses and strengths of each site. Compared with others similar methods, much more criteria (53 parameters) can be considered within this method, so the results will be more calculable. According to this method, Rasht landfill (site H) is classified as unacceptable landfill site i.e. there is an urgent need for a new suitable site for landfill, while Andishe Landfill (site D) is ranked as acceptable landfill site but needs environmental management program to handle the existing weaknesses.

Understanding whether and to what extent ecosystem functions respond to chemicals is a major challenge in environmental toxicology. The available data gathered by ecosystem-level experiments (micro- and mesocosms) often describe the responses of taxa densities to stress. However, whether these responses are proportional to the responses of associated ecosystem functions to stress is unclear. By combining a carbon budget modeling technique with data from a standardized microcosm experiment with a known community composition, we quantified three ecosystem functions (net primary production [NPP], net mesozooplankton production [NZP], and net bacterial production [NBP]) at three Cu concentrations, with a control. Changes of these ecosystem functions with increasing chemical concentrations were not always proportional to the Cu effects on the densities of the contributing functional groups. For example, Cu treatments decreased mesozooplankton density by 100-fold and increased phytoplankton density 10- to 100-fold while increasing NZP and leaving NPP unaltered. However, in contrast, Cu affected microzooplankton and the associated function (NBP) in a comparable way. We illustrate that differences in the response of phytoplankton/mesozooplankton densities and the associated ecosystem functions to stress occur because functional rates (e.g., photosynthesis rates/ingestion rates) vary among Cu treatments and in time. These variations could be explained by food web ecology but not by direct Cu effects, indicating that ecology may be a useful basis for understanding environmental effects of stressors., (Copyright © 2011 SETAC.)

Ecotoxicity data with high reliability and relevance are needed to guarantee the scientific quality of environmental risk assessments of pharmaceuticals. The main advantages of a more structured approach to data evaluation include increased transparency and predictability of the risk assessment process, and the possibility to use non-standard data. In this collaboration, between the research project MistraPharma and the German Federal Environment Agency, a new set of reporting and evaluation criteria is presented and discussed. The new criteria are based on the approaches in the literature and the OECD reporting requirements, and have been further developed to include both reliability and relevance of test data. Intended users are risk assessors and researchers performing ecotoxicological experiments, but the criteria can also be used for education purposes and in the peer-review process for scientific papers. This approach intends to bridge the gap between the regulator and the scientist's needs and way of work., (Copyright © 2011 Elsevier Ltd. All rights reserved.)