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Medicines are essential to human health but can also impact the aquatic and terrestrial environment after use by patients and release via excreta into wastewater. We highlight the need for a GREENER approach to identify and meet important environmental criteria, which will help reduce the impact of medicinal residues on the environment. These criteria include effect reduction by avoiding nontarget effects or undesirable moieties, exposure reduction via lower emissions or environmental (bio)degradability, no PBT (persistent, bioaccumulative, and toxic) substances, and risk mitigation. With all of these criteria, however, patient health is of primary importance as medicines are required to be safe and efficacious for treating diseases. We discuss the feasibility of including these criteria for green by design active pharmaceutical ingredients in the process of drug discovery and development and which tools or assays are needed to accomplish this. The integrated GREENER approach can be used to accelerate discussions about future innovations in drug discovery and development.

The ability to determine accurately the fate of APIs in soil is essential for rigorous risk assessment associated with wastewater reuse or biosolid recycling to land, particularly in lower income countries where water and fertiliser is scarce. Four APIs (naproxen, ofloxacin, propranolol and nevirapine) with wide ranging functionality were used as examples in the development of the OECD 106 soil partitioning and/or degradation study, with naproxen used to illustrate applying the full methodology. The data showed key methodological criteria require careful consideration and testing to generate accurate and consistent results. Only glass fibre membranes were suitable for all APIs, without unduly adsorbing APIs to their surface, thus effectively restricting the minimum practical pore size to 0.7 µm. Polypropylene plastic centrifuge tubes were shown to be suitable, with careful determination of recoveries. Direct injection liquid chromatography-mass spectrometry could reliably resolve all 4 APIs down to less than µg L−1 in soil solutions, although allowance for matrix effects via standard additions was required in some cases. Greatest analytical challenges were found for the highest molecular weight API with the greatest affinity for sorption to surfaces (ofloxacin). Key variables that can impact on partitioning such as solution pH and dissolved organic carbon concentrations were shown to vary within tests over time and should be accounted for.

There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance.1. The workshop was organized and supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), the Swedish Research Council (SRC) and the Centre for Antibiotic Resistance Research at University of Gothenburg, Sweden (CARe). This project received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement JPI-EC-AMR No 681055. Individual member states of the JPIAMR also covered travel costs for participants. Sí

A framework is presented that is intended to facilitate the evaluation of potential aquatic ecological risks resulting from discharges of down the drain chemicals. A scenario is presented using representatives of many of the types of chemicals that are treated domestically. Predicted treated effluent chemical concentrations (PECS) are based on reported loading rates and routine removal rates for three types of treatment: trickling filter (TF), activated sludge secondary treatment (AS), and AS plus advanced oxidation process (AOP). In Tier I, PECs were compared with the lowest predicted no effect concentration (PNEC) obtained from the literature using safety factors as needed. A cumulative risk characterization ratio (cumRCR) 1.0 for all three treatment types in our scenario, even though no chemical exceeded a hazard quotient of 1.0 in AS or AOP. In Tier 2, AS yielded a lower cumRCR than TF due to higher removal rates and the cumRCR in AOP was <

Concentrating cells from aqueous samples is a common requirement for the enumeration of biomass, investigations of microbial diversity and detection of relatively rare organisms in the environment. Accurately representing the initial sampled environments in the concentrated cells is of particular importance when the subsequent analyses have tangible environmental, economic and societal consequences, as is the case with environmental exposure and risk assessment of chemicals. This study investigated the potential use of four different cell concentration methods: centrifugation, membrane filtration, tangential flow filtration and column colonisation. These methods were assessed against a series of scientific and practical criteria, including: similarity of concentrated community to initial environmental sample; cell concentration achieved; biodegradation test outcome; sample throughput; and capital and maintenance costs. All methods increased cell concentration by as little as 10-fold to as much as 1000-fold. DGGE and 454 pyrosequencing analysis showed concentrated communities to have >60% similarity to each other, and the initial sample. There was a general trend for a more reliable assessment of 4-nitrophenol biodegradation in 96-well plate biodegradation assays, with increasing cell concentration. Based on the selection criteria, it is recommended that there is not one concentration method fit for all purposes, rather, the appropriate method should be selected on a case-by-case basis. Membrane filtration would be the most suitable method for low sample volumes; the increased throughput capacity of tangential flow filtration renders it most suitable for large volumes; and centrifugation is most suitable for samples with high initial biomass concentrations. The poor similarity in microbial community composition of the column colonised samples compared to the initial samples, suggested a concentration basis; this combined with its low sample throughput precluded this approach for future concentration studies of planktonic bacterial samples., Graphical abstract Unlabelled Image, Highlights • Methods suitable for concentrating environmental samples are available; • Selecting a suitable method is a pragmatic choice, based on the environment sampled; • Column colonisation appears to introduce bias, possibly promoting biofilm formation; • Increased inoculum concentrations result in more reliable biodegradation assessment.

Comprehensive assessment of environmental biodegradability of pollutants is limited by the use of low throughput systems. These are epitomized by the Organisation for Economic Cooperation and Development (OECD) Ready Biodegradability Tests (RBTs), where one sample from an environment may be used to assess a chemical’s ability to readily biodegrade or persist universally in that environment. This neglects the considerable spatial and temporal microbial variation inherent in any environment. Inaccurate designations of biodegradability or persistence can occur as a result. RBTs are central in assessing the biodegradation fate of chemicals and inferring exposure concentrations in environmental risk assessments. We developed a colorimetric assay for the reliable quantification of suitable aromatic compounds in a high throughput biodegradation screening test (HT-BST). The HT-BST accurately differentiated and prioritized a range of structurally diverse aromatic compounds on the basis of their assigned relative biodegradabilities and quantitative structure–activity relationship (QSAR) model outputs. Approximately 20 000 individual biodegradation tests were performed, returning analogous results to conventional RBTs. The effect of substituent group structure and position on biodegradation potential demonstrated a significant correlation (P < 0.05) with Hammett’s constant for substituents on position 3 of the phenol ring. The HT-BST may facilitate the rapid screening of 100 000 chemicals reportedly manufactured in Europe and reduce the need for higher-tier fate and effects tests.\ud \ud

This is the report of the first workshop on the Validation of Toxicogenomics-based Test Systems held in Ispra, Italy on 11-12 December 2003. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicological test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technological experts, regulators, and the principal validation bodies, and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would serve as the basis for the future validation of the technology when it reached the appropriate stage. Due to the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas included (a) biological validation of toxicogenomics-based test methods for regulatory decision-making, (b) technical and bioinformatics aspects related to validation, and (c) validation issues as they relate to regulatory acceptance and utilization of toxicogenomics-based test methods. This report summarizes the discussions and details the recommendations for future direction and priorities., JRC.I.2-Validation of biomedical testing methods