Current Organic Chemistry - Volume 18, Issue 17, 2014

The last century staged a dramatic change in the way people live and interact with the surrounding environment. A shift from an outdoor to an indoor lifestyle took place and, presently, we spend the majority of our existence inside buildings. From our early days in the kindergarten, to our teens in the school, our adulthood in the workplace and our old age in nursing homes, not forgetting “transit times” inside transportation, 80 to 90% of a person’s time is spent indoors [1]. As elegantly pinpointed by Kelley & Gibert [2], “the built environment constitutes the modern ecological habitat of Homo sapiens”. This new habitat exhibits unique characteristics (e.g., isolation, illumination, humidity) that promotes the accumulation of, not only biological agents (e.g., bacteria, fungi), but also chemical contaminants, therefore representing the prime interface between such agents and humans. All these facts stress the need to monitor and assess indoor environmental quality. This evaluation can be achieved by quantifying chemicals of concern in indoor air, for instance. However, such measurements tend to represent a limited time frame. Furthermore, deleterious effects of chemical exposure in humans are, in their majority, a consequence of chronic exposure. Therefore, long-term evaluations are essential. Indoor dust, by providing integrative measurements of chemical exposure, reveals itself as a suitable matrix to investigate indoor contamination [3]. Chemicals tend to settle in dust that acts not only as a concentrator but also as a repository of contaminants [4]. Moreover, dust is generally regarded as “something worthless” [5] and therefore indoor dust samples are easy to obtain. Despite all these facts, the use of dust in indoor environmental quality surveys and particularly in epidemiological studies is still in its infancy [3]. This thematic issue aims to gather the available information on the levels of contaminants of concern in indoor dust and to further strengthen/encourage the use of this quite unique matrix in exposure assessment studies. An attempt was made to select those compounds that were included in the “health ranking list of semi-volatile organic compounds (SVOCs) ingested through house dust” proposed by Bonvallot and colleagues [6]. The papers here presented are authored by renowned specialists in the SVOCs under appraisal and provide an exciting new perspective on the presence of these contaminants in our everyday life. The occurrence of phenolic endocrine disrupting chemicals (EDCs), including bisphenol A (BPA), tetrabromobisphenol A (TBBPA), phthalates and parabens, in indoor dust is for the first time reviewed on a worldwide basis by Dr. Kannan and co-workers. In their thorough review, the physico-chemical characteristics of these compounds are described and a perspective on the different analytical approaches for phenolic EDCs quantification is also provided. The paper by Dr. Coelhan and Dr. Hilger reviews the occurrence of chlorinated paraffins, a group of chemicals included in the health ranking list of SVOCs [6] for which limited information is available. Their review describes this group of contaminants in terms of production, use, physico-chemical and toxicological properties and also summarizes the available analytical techniques. The levels and human exposure to perfluoroalkyl substances (PFASs) in dust are reviewed by Dr. Nadal and Dr. Domingo. These authors gathered all the available information on the concentrations of PFASs, particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), in indoor dust samples. They further reviewed the data on human exposure in order to understand the role of dust ingestion as an exposure pathway to this class of emerging contaminants. Dr. Isobe and co-workers present a thorough assessment on the recent levels of brominated flame retardants (BFRs) in indoor dust. In contrast with the other groups of contaminants addressed in this thematic issue, BFRs are amongst the most well studied chemicals in dust and therefore the number of surveys is vast. In order to provide an up to date perspective of the global contamination by BFRs in the indoor environment, these authors compiled the most recent information on the concentrations of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in dust samples from different origins (houses, offices, public locations and cars) and geographical locations. The final paper in this issue by Dr. Suzuki and colleagues provides a new perspective on the effects based approach to evaluate toxicity mechanisms in indoor dust samples. By using in vitro bioassays alongside with instrumental analysis, their approach enables to detect the presence and the activity profile of indoor dust contaminants. We are grateful to all the authors who have contributed to this thematic issue and to the Bentham Editorial office staff for their assistance. We also manifest our gratitude towards all the reviewers for contributing with their time and expertise to this mini hot topic. We hope that this thematic issue can be of interest for researchers from a broad range of disciplines including chemistry, epidemiology and related environmental sciences.

Dust from indoor environments can contain significant amounts environmental contaminants and is an important source of human exposure to several toxicants. In this article, studies on the occurrence of several emerging environmental contaminants, namely bisphenol A (BPA), tetrabromobisphenol A (TBBPA), phthalates, parabens, and other environmental phenolic compounds in indoor dust from various countries, were reviewed. Issues associated with sampling of dust and the uncertainties introduced in the analytical procedures were also summarized. Finally, exposure to environmental phenolic compounds through dust ingestion was evaluated, and the contribution of indoor dust to the total daily exposure of toxicants was estimated. Overall, the reported concentrations of target chemicals in dust were found, in decreasing order, as phthalates (overall mean: 949 ± 669 µg/g, range: 0.9-10,900 µg/g) >>> nonylphenol (8.9 ± 6.8 µg/g, 2.6-29.2 µg/g) > BPA (3.6 ± 4.5 µg/g, 0.35-16.6 µg/g) >Σparabens (1.53 ± 0.52 µg/g, 0.03-125 µg/g) > pentachlorophenol (1.39 ± 2.31 µg/g, 0.050- 5.76 µg/g) > triclosan (0.65 ± 0.23 µg/g, 0.38-0.93 µg/g) > TBBPA (0.18 ± 0.14 µg/g, 0.049-0.505 µg/g). Despite the elevated levels of the target phenolic compounds reported in indoor dust, exposure of humans through dust ingestion was minor. Nevertheless, dust can be a significant source of exposure to phenolic compounds for infants and toddlers. Elevated levels of phenolic compounds were found in dust collected from certain microenvironments such as offices and laboratories.

Perfluoroalkyl substances (PFASs) are emerging pollutants whose scientific knowledge has notably increased in the last two decades. Detectable amounts of PFASs, and particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), have been found in the environment, wildlife and humans. Nowadays, the presence of PFASs and its global distribution is well known. However, there is still a high degree of uncertainty in the pathways of exposure through which PFASs enter the human body. Similarly to “classical” persistent organic pollutants (POPs), dietary intake seems to be the predominant exposure route, with water consumption being identified as a potentially important pathway. Since most human exposure to PFASs occurs in indoor environments, the inhalation of indoor air and the ingestion of dust might notably contribute to the total intake of PFASs. In fact, some investigations point out the possibility that, because of higher dust ingestion rates, the PFAS exposure for toddlers could be much higher than that for adults. Even more, the children intake of PFASs could be dominated by dust ingestion, instead of food as the most important exposure pathway. In this paper, we review a number of recent of studies reporting concentrations of PFASs in dust and estimations on the human exposure via dust ingestion. An important geographical variation among countries was observed, therefore indicating that the assessment of this pathway should be performed in a case-by-case basis.

Chlorinated paraffins (CPs), which are also called polychloroalkanes, are chlorination products of n-alkane mixtures. They are classified according to their chain length as short chain (C10-C13), medium chain (C14-C17), and long chain (C20-C30) CPs. The degree of chlorination varies between 30 and over 70%. Considering China, India, U.S.A. and the European Union Countries the current production amount is estimated to be 900,000 t/a. CPs are extremely complex mixtures due to the possibility of the formation of numerous compounds during chlorination. CPs are widely used as flame retardants and additives in metal-working fluids, paints, and sealants as well as plasticizers in plastics. Although data regarding the occurrence of CPs in indoor dust samples are very limited, CPs were detected in the majority of the samples analyzed.

Modern people spend a considerable time of their life indoors, whether at home, at the workplace or at school, or inside vehicles and public transportation, therefore exposure to a variety of contaminants present indoors is constant and profuse. These contaminants released from household products tend to accumulate and concentrate in dust which is thus considered as one of the main human exposure pathways to several chemicals either by inhalation or ingestion. Within this wide range of contaminants polybrominated diphenyl ethers and hexabromocyclododecanes are included. These two brominated flame retardants have been applied in a vast range of materials with the aim to inhibit or delay the combustion and prevent the fire progression thus increasing the available time for people to escape. The extensive usage granted them a ubiquitous presence in the indoor environment and also in humans. Due to their toxicity and their potential to bioaccumulate these flame retardants have been restricted or banned. However, their persistency in the environment and the increasing evidences of deleterious effects towards humans and wildlife renders the study of these contaminants a matter of great importance. In this review we gathered available information on the levels of PBDEs and HBCDs in indoor dust samples collected from different places and different regions around the world and discuss human exposure to these contaminants through dust.

Indoor dust is a sink for many kinds of pollutants, including flame retardants (FRs), plasticizers and various degradation products, derived from household products. Recently, we have put particular emphasis on the evaluation of indoor dust as an excellent indicator of important contaminants for chemical risk management throughout the lifecycle of household product. Our research has focused on effect-based approach using in vitro bioassays together with instrumental analyses in an attempt to conduct hazard characterization determining the presence and activity profile of contaminants detected in house dust. This approach will lead to a determination of priority pollutants, their impurities and by-products for further assessment from the list of chemicals manufactured and distributed worldwide. Here, we introduce some background studies and results obtained by using effect-based approach for house dust, revealing importance of dioxin-like compounds, thyroid and reproductive toxicants used and contained in household products. Based on outcomes from previous studies here summarized, it can be suggested that effect-based approach is a useful scheme to determine contaminants and endpoints in indoor dust for priority assessment on in vitro toxicological point of view. Further integration of exposure and effect analysis for indoor dust will lead to appropriate chemical risk management throughout various household products’ lifecycles.

β-Amino-α-ketoamides 1 are a class of compounds exhibiting biological activity as reversible covalent enzyme inhibitors. The representative examples are clinically approved drugs for the treatment of hepatitis C virus Boceprevir 2 and Telaprevir 3. β-Amino-α- ketoamide substructure is also found in a number of natural products, many of which display a remarkable biological activity. The methods for the synthesis of β-amino-α-ketoamide can be classified based on the key steps of the synthetic routes: from unsaturated amide involving epoxydation followed by a regioselective azidolysis; from esters involving aminohydroxylation; from adehydes via Passerini reaction, cyanohydrin formation, addition of the masked acylcyanide (MAC) reagent or orthothioester; from imines via addition of dithiolane derived from oxoacetic acid, addition of isoxazolyl-4-triflates or via azetidinone formation; from acids via acylation of (cyanomethylene) triphenylphosphorane (the Wasserman procedure), via acylfurane formation or via Dakin-West reaction; from nitroalkanes via Henry reaction. In this review, the information from the scientific literature published within the period from 1990 till 2014 for the synthesis of β-amino-α-ketoamides is covered and systematized according to the above mentioned key steps.

Bio-functional microspheres (BFMs), including drug carrier microspheres, fluorescence microspheres, magnetic microspheres, immune microspheres, enzyme immobilization microspheres, solid-phase synthesis microspheres, and molecular imprinting microspheres, are core-shell microspheres containing bio-molecules and functional materials in their structures. Because of the presence of core-shell structures and spherical shapes, BFMs bear many unique functions and fascinating properties. The research on BFMs has surprisingly blossomed during recent decades. In this review, we give a systematic, balanced and comprehensive summary of the main aspects of BFMs related to their preparation and application, and propose perspectives for future developments of BFMs.

A new strategy for the synthesis of trans- and cis + trans-3,4,5-trisubstituted isoxazolines from allyl compounds of QCH2CH=CH2 type (Q = PhO, 2,2’-bithiophen-5-yl, BuO, Me3CS, PhN(COMe) and others) has been developed. The dipolarophiles are prepared via: a) Ru-carbene catalysed metathesis of Qallyl; b) catalytic isomerization followed by Ru-carbene mediated metathesis; c) Ru-carbene catalysed metathesis followed by isomerization. 1,3-dipolar cycloaddition of nitrile oxide to dipolarophiles obtained via route a), b) or c), including high pressure activated reactions leads to 3,4,5-trisubstituted isoxazolines. Quantitative E-stereoselective homometathesis of some QCH2CH=CH2 to (E)-QCH2CH=CHCH2Q and new highly effective ruthenium and basic catalytic systems for the isomerization of allyl compounds have also been presented. Moreover, easily available (Z)-XCH2CH=CHCH2X allyl compounds were used for the synthesis of cis-3,4,5-trisubstituted isoxazolines. It has been proved by in vitro tests that some of the isoxazolines show interesting antifungal activity comparable to that of fluconazole.