Application of Effect-Based Methods to Water Quality Monitoring: Answering Frequently Asked Questions by Water Quality Managers, Regulators, and Policy Makers

Effect-based methods (EBM) have great potential for water quality monitoring as they can detect the mixture effects of all active known and unknown chemicals in a sample, which cannot be addressed by chemical analysis alone. To date, EBM have primarily been applied in a research context, with a lower level of uptake by the water sector and regulators. This is partly due to concerns regarding the reliability and interpretation of EBM. Using evidence from the peer-reviewed literature, this work aims to answer frequently asked questions about EBM. The questions were identified through consultation with the water industry and regulators and cover topics related to the basis for using EBM, practical considerations regarding reliability, sampling for EBM and quality control, and what to do with the information provided by EBM. The information provided in this work aims to give confidence to regulators and the water sector to stimulate the application of EBM for water quality monitoring.Full Tex

BDE-47 and 6-OH-BDE-47 modulate calcium homeostasis in primary fetal human neural progenitor cells via ryanodine receptor-independent mechanisms

Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants found in rising concentrations in human tissue. Epidemiological and animal studies have raised concern for their potential to induce developmental neurotoxicity (DNT). Considering the essential role of calcium homeostasis in neurodevelopment, PBDE-induced disturbance of intracellular calcium concentration ([Ca(2+)]i) may underlie PBDE-induced DNT. To test this hypothesis, we investigated acute effects of BDE-47 and 6-OH-BDE-47 on [Ca(2+)]i in human neural progenitor cells (hNPCs) and unraveled involved signaling pathways. Short-time differentiated hNPCs were exposed to BDE-47, 6-OH-BDE-47, and multiple inhibitors/stimulators of presumably involved signaling pathways to determine possible effects on [Ca(2+)]i by single-cell microscopy with the fluorescent dye Fura-2. Initial characterization of calcium signaling pathways confirmed the early developmental stage of hNPCs. In these cells, BDE-47 (2 μM) and 6-OH-BDE-47 (0.2 μM) induce [Ca(2+)]i transients. This increase in [Ca(2+)]i is due to extracellular Ca(2+) influx and intracellular release of Ca(2+), mainly from the endoplasmic reticulum (ER). While extracellular Ca(2+) seems to enter the cytoplasm upon 6-OH-BDE-47 by interfering with the cell membrane and independent of Ca(2+) ion channels, ER-derived Ca(2+) is released following activation of protein lipase C and inositol 1,4,5-trisphosphate receptor, but independently of ryanodine receptors. These findings illustrate that immature developing hNPCs respond to low concentrations of 6-OH-BDE-47 by an increase in [Ca(2+)]i and provide new mechanistic explanations for such BDE-induced calcium disruption. Thus, these data support the possibility of a critical window of PBDE exposure, i.e., early human brain development, which has to be acknowledged in risk assessment

In vitro techniques for assessing neurotoxicity using human IPSC-derived neuronal models

The central nervous system consists of a multitude of different neurons and supporting cells that form networks for transmitting neuronal signals. Proper function of the nervous system depends critically on a wide range of highly regulated processes including intracellular calcium homeostasis, neurotransmitter release, and electrical activity. Due to the diversity of cell types and complexity of signaling processes, the (central) nervous system is very vulnerable to toxic insults. Nowadays, a broad range of approaches and cell models is available to study neurotoxicity. In this chapter we show the applicability of human induced pluripotent stem cell (hiPSC)-derived neuronal co-cultures for in vitro neurotoxicity testing. We demonstrate that immunocytochemistry can be used to visualize networks of cultured cells and to differentiate between different cell types. Live cell imaging and electrophysiology techniques demonstrate that the neuronal networks develop spontaneous activity, including synchronized calcium oscillations that coincide with spontaneous changes in membrane potential as well as spontaneous electrical activity with defined (network) bursting. Importantly, as shown in this chapter, spontaneously active human iPSC-derived neuronal co-cultures are suitable for in vitro neurotoxicity assessment. Future application of live imaging and electrophysiological techniques on hiPSC from different donors and/or patients differentiated in different cell types holds great promise for personalized neurotoxicity assessment and safety screening

The Regulatory Roles of MicroRNA in Effects of 2,2'4,4'-Tetrabromodiphenyl Ether (BDE47) on the Transcriptome of Zebrafish Larvae

The developmental neurotoxicity caused by environmental pollutants has received great concern; however, there were still barely known about the underlying toxic mechanisms, especially the influence of varieties of regulatory factors such as microRNA (miRNA). A representative flame retardant, 2,2',4,4'-tetrabromodiphenyl ether (BDE47), was found to disrupt zebrafish development in visual perception and bone formation in previous study, thus here we investigated its effects on miRNA expression profiling of 6 days post fertilization (dpf) zebrafish larvae by deep sequencing. To overcome the shortage of zebrafish miRNA annotation, multiple data processing approaches, especially constructed network based on the interactions between miRNAs and enrichment terms, were adopted and helped us acquire several validated zebrafish miRNAs and two novel miRNAs in BDE47-induced effects, and identify corresponding biological processes of the miRNAs. Among them, miR-735 was supposed to play essential roles in larval sensory development according to analysis results. Our study also provided an effective strategy for analyzing biological effects on non-mammalian miRNAs with limited basic information

Soil Pollution and Remediation

The management of solid waste is one of the challenges facing any urban area in the world. Although in developing countries the quantity of solid waste generated in urban areas is low compared to industrialized countries, the municipal solid waste management (MSWM) still remains inadequate. A typical solid waste management system in a developing country displays an array of problems, including low collection coverage and irregular collection services, crude open dumping and burning without air and water pollution control, etc. This segment of the research deals with the issue of remediation of contaminated sites, with special emphasis on areas contaminated with pollutants originating from the disposal of solid waste streams. The need for implementation of the research comes from the results of qualitative and quantitative analysis of organic and inorganic pollutants in the soil conducted by our team. Soil conservation is fundamental for the sustainable development and preservation of ecosystems and biodiversity. Heavy metal concentration in the soil dependent on the parent material on which it is formed, the formation processes, and the composition and proportion of the components of the solid phase. This concentration may be affected by several anthropic activities such as: irrigation, fertilizer and chemical applications, and industrial or urban sewage incorporation. The soil type, topography, geology, and the erosive processes influence the concentration and distribution of heavy metals in the environment, including their bioavailability. The main objective of this part of study was to assess the origin of the heavy metals in the soil. Persistent organic pollutants (POPs) are another group of pollutants in the soil. Sources of pollution from POPs include the incorrect use and/or disposal of agrochemicals and industrial chemicals and improper burning. There are eight initial POPs pesticides (aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex, and toxaphene) and five new POPs chemicals which may be categorized as pesticides (alpha hexachlorocyclohexane, beta hexachlorocyclohexane, chlordecone, lindane, and pentachlorobenzene). Because of their widespread distribution and their potential toxicity to organisms, these compounds are of environmental significance. In present study were also included some POPs chemicals originating from industry such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and polyaromatic hydrocarbons (PAHs). Third part of the study covers methods for soil sampling, sample preparation, and instrumental analysis of agrochemical and industrial POPs