Identification of groundwater nitrate sources in an urban aquifer (Alborz Province, Iran) using a multi-parameter approach.

High concentrations of NŌ in water resources are detrimental to both human health and aquatic ecosystems. Identification of NŌ sources and biogeochemical processes is a crucial step in managing and controlling NŌ pollution. In this study, land use, hydrochemical data, dual stable isotopic ratios and Bayesian Stable Isotope Mixing Models (BSIMM) were integrated to identify NŌ sources and estimate their proportional contributions to the contamination of the Karaj Urban Aquifer (Iran).

Determining nitrate pollution sources in the Kabul Plain aquifer (Afghanistan) using stable isotopes and Bayesian stable isotope mixing model.

The Kabul urban aquifer (Afghanistan), which is the main source of drinking water for Kabul city's inhabitants, is highly vulnerable to anthropogenic pollution. In this study, the geochemistry of major ions (including reactive nitrogen species such as NO, NO-, and NH) and stable isotope ratios (δN-NO, δO-NO, δO-HO, and δH-HO) of surface and groundwater samples from the Kabul Plain were analyzed over two sampling periods (dry and wet seasons). A Bayesian stable isotope mixing model (BSIMM) was also employed to trace potential nitrate sources, transformation processes, and proportional contributions of nitrate sources in the Kabul aquifer.

Application of text mining to develop AOP-based mucus hypersecretion genesets and confirmation with in vitro and clinical samples.

Mucus hypersecretion contributes to lung function impairment observed in COPD (chronic obstructive pulmonary disease), a tobacco smoking-related disease. A detailed mucus hypersecretion adverse outcome pathway (AOP) has been constructed from literature reviews, experimental and clinical data, mapping key events (KEs) across biological organisational hierarchy leading to an adverse outcome. AOPs can guide the development of biomarkers that are potentially predictive of diseases and support the assessment frameworks of nicotine products including electronic cigarettes.

Feeding dicyandiamide (DCD) to cattle: An effective method to reduce NO emissions from urine patches in a heavy-textured soil under temperate climatic conditions.

Nitrate (NO) leaching and nitrous oxide (NO) emission from urine patches in grazed pastures are key sources of water and air pollution, respectively. Broadcast spraying of the nitrification inhibitor dicyandiamide (DCD) has been shown to reduce these losses, but it is expensive. As an alternative, it had been demonstrated that feeding DCD to cattle (after manual mixing with supplementary feeds) was a practical, effective and cheaper method to deliver high DCD rates within urine patches.

In vitro RNA-seq-based toxicogenomics assessment shows reduced biological effect of tobacco heating products when compared to cigarette smoke.

The battery of regulatory tests used to evaluate the risk of novel tobacco products such as heated tobacco products (THPs) presents some limitations including a bias towards the apical endpoint tested, and limited information on the mode of action. This is driving a paradigm shift to more holistic systems biology approaches. In this study, we used RNA-sequencing to compare the transcriptomic perturbations following acute exposure of a 3D airway tissue to the aerosols from two commercial THPs and a reference 3R4F cigarette.

Assessing modified risk tobacco and nicotine products: Description of the scientific framework and assessment of a closed modular electronic cigarette.

Cigarette smoking causes many human diseases including cardiovascular disease, lung disease and cancer. Novel tobacco products with reduced yields of toxicants compared to cigarettes, such as tobacco-heating products, snus and electronic cigarettes, hold great potential for reducing the harms associated with tobacco use. In the UK several public health agencies have advocated a potential role for novel products in tobacco harm reduction.

Combining stable isotopes with contamination indicators: A method for improved investigation of nitrate sources and dynamics in aquifers with mixed nitrogen inputs.

Excessive nitrate (NO) concentration in groundwater raises health and environmental issues that must be addressed by all European Union (EU) member states under the Nitrates Directive and the Water Framework Directive. The identification of NO sources is critical to efficiently control or reverse NO contamination that affects many aquifers. In that respect, the use of stable isotope ratios N/N and O/O in NO (expressed as δN-NO and δO-NO, respectively) has long shown its value.

Mass Spectrometry and Luminogenic-based Approaches to Characterize Phase I Metabolic Competency of In Vitro Cell Cultures.

Xenobiotic metabolizing enzymes play a key function in the biotransformation of medicines and toxicants by adding functional groups that increase solubility and facilitate excretion. On some occasions those structural modifications lead to the formation of new toxic products. In order to reduce animal testing, chemical risk can be assessed using metabolically competent cells.

Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics.

Electronic cigarettes (e-cigarettes) use has increased globally and could potentially offer a lower risk alternative to cigarette smoking. Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were generated with standard intense smoking regimens with careful consideration for dose by normalizing the exposures to nicotine.

Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers.

Aim: Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events.

Results: A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC-MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases.

Improving and disaggregating N2O emission factors for ruminant excreta on temperate pasture soils.

Cattle excreta deposited on grazed grasslands are a major source of the greenhouse gas (GHG) nitrous oxide (N2O). Currently, many countries use the IPCC default emission factor (EF) of 2% to estimate excreta-derived N2O emissions. However, emissions can vary greatly depending on the type of excreta (dung or urine), soil type and timing of application.

Targeted omics analyses, and metabolic enzyme activity assays demonstrate maintenance of key mucociliary characteristics in long term cultures of reconstituted human airway epithelia.

3D reconstituted respiratory epithelia have emerged as better in vitro models for toxicological testing compared to cell lines due to the conservation of key morphological features and functions. MucilAir™ is a commercially available human airway epithelia system that can potentially maintain functional attributes for up to a year, however, detailed mucociliary characteristics and xenobiotic metabolism relevant to inhaled pro-toxicant bioactivation is lacking. Here, we assessed in MucilAir™ some key biomarkers that are characteristic of the respiratory epithelia including morphology, function and xenobiotics metabolism.

Quantification of plasma microRNAs in a group of healthy smokers, ex-smokers and non-smokers and correlation to biomarkers of tobacco exposure.

The stability of circulating miRNAs, their non-invasive sampling techniques and deregulation in diseases make them potential candidate biomarkers of biological effect. Here, we profiled the level of 84 plasma miRNAs in 30 smokers, 20 non-smokers and 20 ex-smokers. A robust statistical strategy was applied with replicate samples to account for reproducibility of the results.

Application of CE-MS to a metabonomics study of human urine from cigarette smokers and non-smokers.

Background: Novel biomarkers of exposure and early adverse effects are needed for comparative studies of combustible and non-combustible tobacco products for regulatory authority evaluation. Metabolic biomarkers reflect both gene and environmental effects.

Results: CE-MS has been applied to human urine samples from non-smokers and smokers of cigarettes at two tar levels.

Nicotine, cotinine, and b-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG.

Recent in vitro work using purified enzymes demonstrated that nicotine and/or a nicotine metabolite could inhibit CYPs (CYP2A6, 2A13, 2E1) involved in the metabolism of the genotoxic tobacco nitrosamine NNK. This observation raises the possibility of nicotine interaction with the mechanism of NNK bioactivation. Therefore, we hypothesized that nicotine or a nicotine metabolite such as cotinine might contribute to the inhibition of NNK-induced DNA strand breaks by interfering with CYP enzymes.

Nicotine, cotinine, and β-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG.

Recent in vitro work using purified enzymes demonstrated that nicotine and/or a nicotine metabolite could inhibit CYPs (CYP2A6, 2A13, 2E1) involved in the metabolism of the genotoxic tobacco nitrosamine NNK. This observation raises the possibility of nicotine interaction with the mechanism of NNK bioactivation. Therefore, we hypothesized that nicotine or a nicotine metabolite such as cotinine might contribute to the inhibition of NNK-induced DNA strand breaks by interfering with CYP enzymes.

The effect of nitrification inhibitors on nitrous oxide emissions from cattle urine depositions to grassland under summer conditions in the UK.

Nitrous oxide (N2O) has become the prime ozone depleting atmospheric emission and the third most important anthropogenic greenhouse gas, with a global warming potential approximately 300 times higher than CO2. Nitrification and denitrification are processes responsible for N2O emission from the soil after nitrogen input. The application of a nitrification inhibitor can reduce N2O emissions from these processes.

A correlation study applied to biomarkers of internal and effective dose for acrylonitrile and 4-aminobiphenyl in smokers.

The urinary metabolites 2-cyanoethylmercapturic acid and 4-aminobiphenyl have been correlated with tobacco smoke exposure. Similarly, 2-cyanoethylvaline and 4-aminobiphenyl haemoglobin adducts have been used as biomarkers of effective dose for the exposure to acrylonitrile and 4-aminobiphenyl, respectively. Each pair of biomarkers is derived from the same parent chemical; however, the correlation between the urinary and the haemoglobin biomarkers has not been investigated.

Mustard catch crop enhances denitrification in shallow groundwater beneath a spring barley field.

Over-winter green cover crops have been reported to increase dissolved organic carbon (DOC) concentrations in groundwater, which can be used as an energy source for denitrifiers. This study investigates the impact of a mustard catch crop on in situ denitrification and nitrous oxide (N2O) emissions from an aquifer overlain by arable land. Denitrification rates and N2O-N/(N2O-N+N2-N) mole fractions were measured in situ with a push-pull method in shallow groundwater under a spring barley system in experimental plots with and without a mustard cover crop.

Slow delivery of a nitrification inhibitor (dicyandiamide) to soil using a biodegradable hydrogel of chitosan.

Using chemical inhibitors to reduce soil nitrification decreases emissions of environmental damaging nitrate and nitrous oxide and improves nitrogen use efficiency in agricultural systems. The efficacy of nitrification inhibitors such as dicyandiamide (DCD) is limited in soil due to biodegradation. This study investigated if the persistence of DCD could be sustained in soil by slow release from a chitosan hydrogel.

Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.

There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers.

Metabolic characterization of cell systems used in in vitro toxicology testing: lung cell system BEAS-2B as a working example.

The bioactivation of pro-toxicants is the biological process through which some chemicals are metabolized into reactive metabolites. Therefore, in vitro toxicological evaluation should ideally be conducted in cell systems retaining adequate metabolic competency and relevant to the route of exposure. The respiratory tract is the primary route of exposure to inhaled pro-toxicants and lung-derived BEAS-2B cell line has been considered as a potentially suitable model for in vitro toxicology testing.

Evaluating the utility of 15N and 18O isotope abundance analyses to identify nitrate sources: A soil zone study.

(15)N and (18)O isotope abundance analyses in nitrate (NO(3)(-)) (expressed as δ(15)N-NO(3)(-) and δ(18)O-NO(3)(-) values respectively) have often been used in research to help identify NO(3)(-) sources in rural groundwater. However, questions have been raised over the limitations as overlaps in δ values may occur between N source types early in the leaching process. The aim of this study was to evaluate the utility of using stable isotopes for nitrate source tracking through the determination of δ(15)N-NO(3)(-) and δ(18)O-NO(3)(-) in the unsaturated zone from varying N source types (artificial fertiliser, dairy wastewater and cow slurry) and rates with contrasting isotopic compositions.

A comparative in vitro kinetic study of [14C]-eugenol and [14C]-methyleugenol activation and detoxification in human, mouse, and rat liver and lung fractions.

Eugenol is a natural alkenylbenzene compound used in a variety of consumer products. There is limited evidence for the carcinogenicity of eugenol to experimental animals. However, in vitro tests for the genotoxic potential of eugenol have on occasion reported a positive result.

An inter-laboratory comparison of urinary 3-hydroxypropylmercapturic acid measurement demonstrates good reproducibility between laboratories.

Background: Biomarkers have been used extensively in clinical studies to assess toxicant exposure in smokers and non-smokers and have recently been used in the evaluation of novel tobacco products. The urinary metabolite 3-HPMA, a metabolite of the major tobacco smoke toxicity contributor acrolein, is one example of a biomarker used to measure exposure to tobacco smoke. A number of laboratories have developed liquid chromatography with tandem mass spectrometry (LC-MS/MS) based methods to measure urinary 3-HPMA; however, it is unclear to what extent the data obtained by these different laboratories are comparable.