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BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and [...]

BACKGROUND: In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics--Moving into Regulation and Monitoring, held [...]

This is the report of the first workshop "Validation of Toxicogenomics-Based Test Systems!' held 11-12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the [...]

A sandwich hybridization assay for high-throughput, rapid, simple, and inexpensive quantification of specific microbial populations is explored. The RNA assay has good specificity, permitted discrimination of rRNA sequences that differed by a 2-bp mismatch in the probe target region and distinguished the sizes of ammonia-oxidizing bacteria (AOB) populations in nitrifying and nonnitrifying wastewater treatment plants.

Results show that staining with the fluorescent dye hexidium iodide measures Gram status with both gram-positive and gram-negative bacterial levels ranging from 1.5% in activated sludge flocs to 16% in the activated sludge fluid. The method enables a rapid, quantitative determination of Gram status linked with in situ activity of the bacterial populations within wastewater systems.

Research was conducted to study the purification, gene isolation and characterization of the NADH-dependent glycerol trinitrate (GTN) reductase from Agrobacterium radiobacter. Standard assay conditions were used to determine GTN reductase activity while nitrate esters were evaluated by high-pressure liquid chromatography. Results indicated that the initial step in the bacterial denitration of GTN is reductive, producing nitrite as the first-released nitrogenous product.

Agrobacterium radiobacter stoichiometrically reduces glycerol trinitrate (GTN) to glycerol 1,3- and 1,2-dinitrate. The reaction shows regioselectivity for the formation of glycerol 1,3-dinitrate. The dinitrates are reduced to glycerol 1- and 2-mononitrates which are not degraded further. The bacteria also reduce pentaerythritol tetranitrate (PETN). The activity of the enzyme involved in the biodegradation of GTN and PETN increases in the presence of NADP.

The role of oxygen in the biodegradation pathways of monomethyl sulphate (MMS) is studied for Agrobacterium sp. and Hyphomicrobium sp. by growing them in an electrode chamber. Hyphomicrobium sp. Ms223 is obligatory in its need for O2 for MMS degradation, and this contradicts earlier studies on the organism. Unlike Agrobacterium, the Hyphomicrobium sp. grows on methanol and the cells oxidize methanol but not MMS. Hyphomicrobium MS223 shows a pathway that appears to lack methanol for the biodegradation of MMS and possibly possesses an oxidative mechanism for biodegradation initiation.

The data on microbial metabolism, with special reference to bacteria and protists involved in biodegradation, and on nitrate ester, on which these bacteria react, have been discussed. The synthesis of glycerol trinitrate (GTN) was regarded for long as non-biodegradable, and this was proved inaccurate by studies on mixed cultures in laboratory-scale activated sewage systems. The cleavage of the first nitrate ester linkage in the GTN was proved to take place, with regioselectivity 3:1 favoring attack at the secondary ester.

BACKGROUND: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. OBJECTIVE: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. METHODS: The authors participated in a workshop held 4--8 March 2012 in Quebec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development 'hot spots,' exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. DISCUSSION: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental 'hot spot' compartments; and c) modifying traditional dose--response approaches to address doses of ARB for various health outcomes and pathways. CONCLUSIONS: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multi-criteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers. http://dx.doi.org/10.1289/ehp.1206316, Introduction A workshop (Antimicrobial Resistance in the Environment: Assessing and Managing Effects of Anthropogenic Activities), held in March 2012 in Quebec, Canada, focused on antibiotic resistance in the environment and [...]

BACKGROUND: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. OBJECTIVE: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. METHODS: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. DISCUSSION: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. CONCLUSIONS: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. KEY WORDS: agriculture, antibiotic manufacturing, antibiotic resistance, aquaculture, livestock, manure management, policy, wastewater treatment. Environ Health Perspect 121:878-885 (2013). http://dx.doi. org/10.1289/ehp.1206446 [Online 4 June 2013], Introduction Antibiotic resistance represents a serious and growing human health threat worldwide. In many areas of the world there are no effective antibiotic therapies available for life-threatening infections, and the [...]

The multinational drug company AstraZeneca has a long-standing commitment to proactively manage the environmental risks associated with drug manufacture and products in patient use (see Nature 526, 164; 2015). In [...]

At AstraZeneca we are proactively addressing the problem of pharmaceuticals entering the environment as a result of our manufacturing discharges (Nature 476, 265; 2011). Using ecotoxicity data and our knowledge [...]

Author(s): Bela Tiwari [1]; Dawn Field [1]; Jason Snape [2] Sir We support the suggestion made by Carlos Santos and colleagues in Correspondence (Nature 438, 738; 200510.1038/438738a) that data associated [...]