Faringdon Day Hospital

This review paper reports the consensus of a technical workshop hosted by the European network, NanoImpactNet (NIN). The workshop aimed to review the collective experience of working at the bench with manufactured nanomaterials (MNMs), and to recommend modifications to existing experimental methods and OECD protocols. Current procedures for cleaning glassware are appropriate for most MNMs, although interference with electrodes may occur. Maintaining exposure is more difficult with MNMs compared to conventional chemicals. A metal salt control is recommended for experiments with metallic MNMs that may release free metal ions. Dispersing agents should be avoided, but if they must be used, then natural or synthetic dispersing agents are possible, and dispersion controls essential. Time constraints and technology gaps indicate that full characterisation of test media during ecotoxicity tests is currently not practical. Details of electron microscopy, dark-field microscopy, a range of spectroscopic methods (EDX, XRD, XANES, EXAFS), light scattering techniques (DLS, SLS) and chromatography are discussed. The development of user-friendly software to predict particle behaviour in test media according to DLVO theory is in progress, and simple optical methods are available to estimate the settling behaviour of suspensions during experiments. However, for soil matrices such simple approaches may not be applicable. Alternatively, a Critical Body Residue approach may be taken in which body concentrations in organisms are related to effects, and toxicity thresholds derived. For microbial assays, the cell wall is a formidable barrier to MNMs and end points that rely on the test substance penetrating the cell may be insensitive. Instead assays based on the cell envelope should be developed for MNMs. In algal growth tests, the abiotic factors that promote particle aggregation in the media (e.g. ionic strength) are also important in providing nutrients, and manipulation of the media to control the dispersion may also inhibit growth. Controls to quantify shading effects, and precise details of lighting regimes, shaking or mixing should be reported in algal tests. Photosynthesis may be more sensitive than traditional growth end points for algae and plants. Tests with invertebrates should consider non-chemical toxicity from particle adherence to the organisms. The use of semi-static exposure methods with fish can reduce the logistical issues of waste water disposal and facilitate aspects of animal husbandry relevant to MMNs. There are concerns that the existing bioaccumulation tests are conceptually flawed for MNMs and that new test(s) are required. In vitro testing strategies, as exemplified by genotoxicity assays, can be modified for MNMs, but the risk of false negatives in some assays is highlighted. In conclusion, most protocols will require some modifications and recommendations are made to aid the researcher at the bench.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Bioavailability of metals to aquatic organisms can be considered to be a combination of the physicochemical factors governing metal behavior and the specific pathophysiological characteristics of the organism's biological receptor. Effectively this means that a measure of bioavailability will reflect the exposures that organisms in the water column actually "experience". This is important because it has long been established that measures of total metal in waters have limited relevance to potential environmental risk. The concept of accounting for bioavailability in regard to deriving and implementing environmental water quality standards is not new, but the regulatory reality has lagged behind the development of scientific evidence supporting the concept. Practical and technical reasons help to explain this situation. For example, concerns remain from regulators and the regulated that the efforts required to change existing systems of metal environmental protection that have been in place for over 35 yr are so great as not to be commensurate with likely benefits. However, more regulatory jurisdictions are now considering accounting for metal bioavailability in assessments of water quality as a means to support evidence-based decision-making. In the past decade, both the US Environmental Protection Agency and the European Commission have established bioavailability-based standards for metals, including Cu and Ni. These actions have shifted the debate toward identifying harmonized approaches for determining when knowledge is adequate to establish bioavailability-based approaches and how to implement them.

More than two-thirds of the world's nickel (Ni) lateritic deposits are in tropical regions, and just less than half are within South East Asia and Melanesia (SEAM). With increasing Ni mining and processing in SEAM, environmental risk assessment tools are required to ensure sustainable development. Currently, there are no tropical-specific water or sediment quality guideline values for Ni, and the appropriateness of applying guideline values derived for temperate systems (e.g., Europe) to tropical ecosystems is unknown. Databases of Ni toxicity and toxicity tests for tropical freshwater and sediment species were compiled. Nickel toxicity data were ranked, using a quality assessment, identifying data to potentially use to derive tropical-specific Ni guideline values. There were no data for Ni toxicity in tropical freshwater sediments. For tropical freshwaters, of 163 Ni toxicity values for 40 different species, high-quality chronic data, based on measured Ni concentrations, were found for just 4 species (1 microalga, 2 macrophytes, and 1 cnidarian), all of which were relevant to SEAM. These data were insufficient to calculate tropical-specific guideline values for long-term aquatic ecosystem protection in tropical regions. For derivation of high-reliability tropical- or SEAM-specific water and sediment quality guideline values, additional research effort is required. Using gap analysis, we recommend how research gaps could be filled. Environ Toxicol Chem 2018;37:293-317. © 2017 SETAC.

Concomitant with the increasing denouncement of African game legislation as inappropriate law imposed by a former colonial authority, is the attack upon traditional, i.e. total protection, practice of conservation. It is increasingly argued by a school of neo-populist thinkers, that local people should be allowed to exploit protected areas in accordance with their own traditions and beliefs. Examples of alleged injustice or practice are consistently misrepresented with a view to replacing traditional conservation practice with left-wing political dogma, proponents claiming a mandate from the Caracas 1992 IVth World Congress on National Parks and Protected Areas.

On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants. The work-group members agreed on the following research priorities: a) available data on the ecotoxicology of OE-P and OC should be published; b) risk should be assessed for OC-contaminated river water generating OC-resistant viruses in wildfowl; c) sewage treatment plant functioning due to microbial inhibition by neuraminidase inhibitors and other antimicrobials used during a pandemic should be investigated; and d) realistic worst-case exposure scenarios should be developed. Additional modeling would be useful to identify localized areas within river catchments that might be prone to high pharmaceutical concentrations in sewage treatment plant effluent. Ongoing seasonal use of Tamiflu in Japan offers opportunities for researchers to assess how much OC enters and persists in the aquatic environment.

Recently, there has been renewed interest in the development and use of empirical models to predict metal bioavailability and derive protective values for aquatic life. However, there is considerable variability in the conceptual and statistical approaches with which these models have been developed. In the present study, we review case studies of empirical bioavailability model development, evaluating and making recommendations on key issues, including species selection, identifying toxicity-modifying factors (TMFs) and the appropriate environmental range of these factors, use of existing toxicity data sets and experimental design for developing new data sets, statistical considerations in deriving species-specific and pooled bioavailability models, and normalization of species sensitivity distributions using these models. We recommend that TMFs be identified from a combination of available chemical speciation and toxicity data and statistical evaluations of their relationships to toxicity. Experimental designs for new toxicity data must be sufficiently robust to detect nonlinear responses to TMFs and should encompass a large fraction (e.g., 90%) of the TMF range. Model development should involve a rigorous use of both visual plotting and statistical techniques to evaluate data fit. When data allow, we recommend using a simple linear model structure and developing pooled models rather than retaining multiple taxa-specific models. We conclude that empirical bioavailability models often have similar predictive capabilities compared to mechanistic models and can provide a relatively simple, transparent tool for predicting the effects of TMFs on metal bioavailability to achieve desired environmental management goals. Environ Toxicol Chem 2019;39:85-100. © 2019 SETAC.

Abstract In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. Integr Environ Assess Manag 2017;13:302–316. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC) Key Points The present study is an up-to-date review of the major challenges and potential solutions associated with environmental endocrine testing and assessment. The present study recommends leveraging in silico, in vitro, as well as high-throughput data to the extent possible to prioritize and inform environmental endocrine testing programs. Practical suggestions are made in the present study to guide environmental endocrine testing and improve sensitivity in regard to species, life-stage, and endpoint selection and measurement. Key gaps in endocrine knowledge and assessment techniques are highlighted, with recommendations for future research.

Abstract A SETAC Pellston Workshop® “Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)” was held in February 2016 in Pensacola, Florida, USA. The primary objective of the workshop was to provide advice, based on current scientific understanding, to regulators and policy makers; the aim being to make considered, informed decisions on whether to select an ecotoxicological hazard- or a risk-based approach for regulating a given endocrine-disrupting substance (EDS) under review. The workshop additionally considered recent developments in the identification of EDS. Case studies were undertaken on 6 endocrine-active substances (EAS—not necessarily proven EDS, but substances known to interact directly with the endocrine system) that are representative of a range of perturbations of the endocrine system and considered to be data rich in relevant information at multiple biological levels of organization for 1 or more ecologically relevant taxa. The substances selected were 17α-ethinylestradiol, perchlorate, propiconazole, 17β-trenbolone, tributyltin, and vinclozolin. The 6 case studies were not comprehensive safety evaluations but provided foundations for clarifying key issues and procedures that should be considered when assessing the ecotoxicological hazards and risks of EAS and EDS. The workshop also highlighted areas of scientific uncertainty, and made specific recommendations for research and methods-development to resolve some of the identified issues. The present paper provides broad guidance for scientists in regulatory authorities, industry, and academia on issues likely to arise during the ecotoxicological hazard and risk assessment of EAS and EDS. The primary conclusion of this paper, and of the SETAC Pellston Workshop on which it is based, is that if data on environmental exposure, effects on sensitive species and life-stages, delayed effects, and effects at low concentrations are robust, initiating environmental risk assessment of EDS is scientifically sound and sufficiently reliable and protective of the environment. In the absence of such data, assessment on the basis of hazard is scientifically justified until such time as relevant new information is available. Integr Environ Assess Manag 2017;13:267–279. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC) Key Points This consensus paper, developed using a cross section of international expertise, provides scientific information on current best practices in the evaluation of hazards and risks to wildlife populations of endocrine-active substances (EAS) and endocrine-disrupting substances (EDS). This paper, and the workshop on which it is based, concludes that if EDS data on environmental exposure, effects on sensitive species and life stages, delayed effects, and effects at low concentrations are robust, then environmental risk assessment is scientifically sound and sufficiently reliable. Areas of scientific uncertainty are highlighted and specific recommendations made for research and methods development, based on crosscutting issues that may impact decision making, all emerging from the case studies performed in preparation for the workshop. If suitable test or modeling methods are unavailable, the only alternative may be to regulate the substance on the basis of hazard alone, at least until such time as relevant additional data become available.

Chemical contamination from point source discharges in developed (resource-rich) countries has been widely regulated and studied for decades; however, diffuse sources are largely unregulated and widespread. In the European Union (EU), large dischargers report releases of some chemicals, yet little is known of total emissions (point and diffuse) and their relative significance. We estimated copper loadings from all significant sources including industry, sewage treatment plants, surface runoff (from traffic, architecture, and atmospheric deposition), septic tanks, agriculture, mariculture, marine transport (antifoulant leaching), and natural processes. A combination of European datasets, literature, and industry data were used to generate export coefficients. These were then multiplied by activity rates to derive loads. A total of approximately 8 kt of copper per annum (ktpa) is estimated to enter freshwaters in the EU, and another 3.5 ktpa enters transitional and coastal waters. The main inputs to freshwater are natural processes (3.7 ktpa), agriculture (1.8 ktpa), and runoff (1.8 ktpa). Agricultural emissions are dominated by copper-based plant protection products and farmyard manure. Urban runoff is influenced by copper use in architecture and by vehicle brake linings. Antifoulant leaching from boats (3.2 ktpa) dominates saline water loads of copper. It is noteworthy that most of the emissions originate in a limited number of copper uses where environmental exposure and pathways exist, compared with the bulk of copper use within electrical and electronic equipment and infrastructure that has no environmental pathway during its use. A sensitivity analysis indicated significant uncertainty in data from abandoned mines and urban runoff load estimates. This study provided for the first time a methodology and comprehensive metal load apportionment to European aquatic systems, identifying data gaps and uncertainties, which may be refined over time. Source apportionments using this methodology can inform more cost-effective environmental risk assessment and management. Integr Environ Assess Manag 2023;19:1031-1047. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Concomitant with the increasing denouncement of African game legislation as inappropriate law imposed by a former colonial authority, is the attack upon traditional, i.e. total protection, practice of conservation. It is increasingly argued by a school of neo-populist thinkers, that local people should be allowed to exploit protected areas in accordance with their own traditions and beliefs. Examples of alleged injustice or practice are consistently misrepresented with a view to replacing traditional conservation practice with left-wing political dogma, proponents claiming a mandate from the Caracas 1992 IVth World Congress on National Parks and Protected Areas.

Abstract Australian freshwaters have relatively low water hardness and different calcium (Ca) to magnesium (Mg) ratios compared with those in Europe. The hardness values of a substantial proportion of Australian freshwaters fall below the application boundary of the existing European nickel biotic ligand models (Ni BLMs) of 2 mg Ca/L. Toxicity testing was undertaken using Hydra viridissima to assess the predictive ability of the existing Ni BLM for this species in extremely soft waters. This testing revealed an increased competitive effect of Ca and Mg with Ni for binding to the biotic ligand in soft water (<10 mg CaCO3/L) than at higher water hardness. Modifications were made to the Ni BLM by increasing the binding constants for Ca and Mg at the biotic ligand to account for softer waters encountered in Australia and the more important competitive effect of Ca and Mg on Ni toxicity. To validate the modified Ni BLM, ecotoxicity testing was performed on 5 Australian test species in 5 different natural Australian waters. Overall, no single water chemistry parameter was able to indicate the trends in toxicity to all of the test species. The modified Ni BLMs were able to predict the toxicity of Ni to the test species in the validation studies in natural waters better than the existing Ni BLMs. The present study suggests that the overarching mechanisms defining Ni bioavailability to freshwater species are globally similar and that Ni BLMs can be used in all freshwater systems with minor modifications. Environ Toxicol Chem 2018;37:2566–2574. © 2018 SETAC

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices.

Abstract Diclofenac is a nonsteroidal anti-inflammatory human and veterinary medicine widely detected in European surface waters, especially downstream from Wastewater Treatment Plants. With some notable exceptions, veterinary uses of diclofenac in Europe are greatly restricted, so wastewater is the key Europe-wide exposure route for wildlife that may be exposed via the aquatic environment. Proposed Environmental Quality Standards (EQS) which include an assessment of avian exposure from secondary poisoning are under consideration by the European Commission (EC) to support the aims of the Water Framework Directive (WFD). In this paper we summarise information on avian toxicity plus laboratory and field evidence on diclofenac bioaccumulation and bioconcentration in avian food items. A safe diclofenac threshold value for birds of 3 μg kg −1 wet weight in food was previously derived by the European Medicines Agency and should be adopted as an EQS under the WFD to maintain consistency across European regulations. This value is also consistent with values of 1.16–3.99 µg kg −1 diet proposed by the EC under the WFD. Water-based EQS of 5.4 or 230 ng L −1 in freshwater are derived from these dietary standards, respectively, by the EC and by us, with the large difference caused primarily by use of different values for bioaccumulation. A simple assessment of potential water-based EQS compliance is performed for both of these latter values against reported diclofenac concentrations in samples collected from European freshwaters. This shows that exceedances of the EC-derived EQS would be very widespread across Europe while exceedances of the EQS derived by us are confined to a relatively small number of sites in only some Member States. Since there is no evidence for any declines in European waterbird populations associated with diclofenac exposure we recommend use of conservative EQS of 3 µg kg −1 diet or 230 ng L −1 in water to protect birds from diclofenac secondary poisoning through the food chain.

Abstract Evidence from both laboratory and field studies has shown that currently used synthetic and naturally occurring chemical substances may potentially disrupt invertebrate endocrine systems, although the extent of this in field populations remains unclear. Translating concerns about potential endocrine disrupting chemicals (EDCs) into practical and effective regulatory action is currently hampered by the breadth of invertebrate endocrinology when compared to the better understood vertebrate systems, a lack of fundamental knowledge about the endocrinology of many invertebrate groups, and the resulting uncertainty when making regulatory decisions. This commentary (i) outlines the breadth of invertebrate endocrine pathways for which European Union regulation of potential EDCs may be relevant; (ii) reviews the extent to which current knowledge meets regulatory requirements for invertebrates, including an assessment of the suitability of current invertebrate test guidelines for detecting endocrine modes of action; and (iii) proposes a roadmap towards the regulation of potential EDCs with greater confidence, based on the Adverse Outcome Pathway (AOP) concept and a focus on identifying Molecular Initiating Events (MIEs) within AOPs. We conclude there are no validated tools to determine any invertebrate endocrine mode of action in vitro or in vivo. However, there are commonly used invertebrate toxicity tests which might capture adverse effects that could potentially result from an endocrine mode of action but would not identify the causal mechanisms. Therefore, EU regulatory requirements for the identification of EDCs cannot currently be satisfied for invertebrates, either in general or for the specific invertebrates used in standard ecotoxicological studies. We propose that the most important research need is compilation of a comprehensive list of endocrine-related MIEs across invertebrate taxa via use of high-throughput ‘omics in combination with bioinformatics reverse engineered analyses. Although tractable, such an approach would require significant resource investment for development and implementation.

Silver (Ag) has been shown to exhibit antimicrobial properties; as a result, it is being used increasingly in a wide range of consumer products. With these uses, the likelihood that Ag may enter the environment has increased, predominately via land application of biosolids or irrigation with treated wastewater effluent. The aim of the present study was to investigate the toxicity of Ag to 2 plant species: barley (Hordeum vulgare L. CV Triumph) and tomato (Lycopersicum esculentum) in a range of soils under both leached and unleached conditions. The concentrations that resulted in a 50% reduction of plant growth (EC50) were found to vary up to 20-fold across the soils, indicating a large influence of soil type on Ag toxicity. Overall, barley root elongation was found to be the least sensitive to added Ag, with EC50 values ranging from 51 mg/kg to 1030 mg/kg, whereas the tomato plant height showed higher sensitivity with EC50 values ranging from 46 mg/kg to 486 mg/kg. The effect of leaching was more evident in the barley toxicity results, where higher concentrations of Ag were required to induce toxicity. Variations in soil organic carbon and pH were found to be primarily responsible for mitigating Ag toxicity; therefore, these properties may be used in future risk assessments for Ag to predict toxicity in a wide range of soil types.

Silver (Ag) is being increasingly used in a range of consumer products, predominantly as an antimicrobial agent, leading to a higher likelihood of its release into the environment. The present study investigated the toxicity of Ag to the nitrification process in European and Australian soils in both leached and unleached conditions. Overall, leaching of soils was found to have a minimal effect on the final toxicity data, with an average leaching factor of approximately 1. Across the soils, the toxicity was found to vary by several orders of magnitude, with concentrations of Ag causing a 50% reduction in nitrification relative to the controls (EC50) ranging from 0.43 mg Ag/kg to >640 mg Ag/kg. Interestingly, the dose-response relationships in most of the soils showed significant stimulation in nitrification at low Ag concentrations (i.e., hormesis), which in some cases produced responses up to double that observed in the controls. Soil pH and organic carbon were the properties found to have the greatest influence on the variations in toxicity thresholds across the soils, and significant relationships were developed that accounted for approximately 90% of the variability in the data. The toxicity relationships developed from the present study will assist in future assessment of potential Ag risks and enable the site-specific prediction of Ag toxicity.

Abstract There has been an increased emphasis on incorporating bioavailability-based approaches into freshwater guideline value derivations for metals in the Australian and New Zealand water quality guidelines. Four bioavailability models were compared: the existing European biotic ligand model (European Union BLM) and a softwater BLM, together with 2 newly developed multiple linear regressions (MLRs)—a trophic level-specific MLR and a pooled MLR. Each of the 4 models was used to normalize a nickel ecotoxicity dataset (combined tropical and temperate data) to an index condition of pH 7.5, 6 mg Ca/L, 4 mg Mg/L, (i.e., approximately 30 mg CaCO3/L hardness), and 0.5 mg DOC/L. The trophic level-specific MLR outperformed the other 3 models, with 79% of the predicted 10% effect concentration (EC10) values within a factor of 2 of the observed EC10 values. All 4 models gave similar normalized species sensitivity distributions and similar estimates of protective concentrations (PCs). Based on the index condition water chemistry proposed as the basis of the national guideline value, a protective concentration for 95% of species (PC95) of 3 µg Ni/L was derived. This guideline value can be adjusted up and down to account for site-specific water chemistries. Predictions of PC95 values for 20 different typical water chemistries for Australia and New Zealand varied by >40-fold, which confirmed that correction for nickel bioavailability is critical for the derivation of site-specific guideline values. Environ Toxicol Chem 2021;40:100–112. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Abstract Derivation of bioavailability-based guidelines for nickel in freshwaters after normalization of ecotoxicity data using trophic level-specific multiple linear regression (MLRs). SSD = species sensitivity distribution.

The chronic toxicity of chemicals to fish is routinely assessed by using fish early life stage (ELS) test results. Fish full life cycle (FLC) tests are generally required only when toxicity, bioaccumulation, and persistence triggers are met or when there is a suspicion of potential endocrine-disrupting properties. This regulatory approach is based on a relationship between the results of fish ELS and FLC studies first established more than 35 yrs ago. Recently, this relationship has been challenged by some regulatory authorities, and it has been recommended that more substances should undergo FLC testing. In addition, a project proposal has been submitted to the Organisation for Economic Cooperation and Development (OECD) to develop a fish partial life cycle (PLC) test including a reproductive assessment. Both FLC and PLC tests are animal- and resource-intensive and technically challenging and should therefore be undertaken only if there is clear evidence that they are necessary for coming to a regulatory decision. The present study reports on an analysis of a database of paired fish ELS and FLC endpoints for plant protection product active substances from European Union draft assessment reports and the US Environmental Protection Agency Office of Pesticide Programs Pesticide Ecotoxicity Database. Analysis of this database shows a clear relationship between ELS and FLC responses, with similar median sensitivity across substances when no-observed-effect concentrations (NOECs) are compared. There was also no indication that classification of a substance as a mammalian reproductive toxicant leads to more sensitive effects in fish FLC tests than in ELS tests. Indeed, the response of the ELS tests was generally more sensitive than the most sensitive reproduction NOEC from a FLC test. This analysis indicates that current testing strategies and guidelines are fit for purpose and that there is no need for fish full or partial life cycle tests for most plant protection product active substances.

Urban regions of the world are expanding rapidly, placing additional stress on water resources. Urban water bodies serve many purposes, from washing and sources of drinking water to transport and conduits for storm drainage and effluent discharge. These water bodies receive chemical emissions arising from either single or multiple point sources, diffuse sources which can be continuous, intermittent, or seasonal. Thus, aquatic organisms in these water bodies are exposed to temporally and compositionally variable mixtures. We have delineated source-specific signatures of these mixtures for diffuse urban runoff and urban point source exposure scenarios to support risk assessment and management of these mixtures. The first step in a tiered approach to assessing chemical exposure has been developed based on the event mean concentration concept, with chemical concentrations in runoff defined by volumes of water leaving each surface and the chemical exposure mixture profiles for different urban scenarios. Although generalizations can be made about the chemical composition of urban sources and event mean exposure predictions for initial prioritization, such modeling needs to be complemented with biological monitoring data. It is highly unlikely that the current paradigm of routine regulatory chemical monitoring alone will provide a realistic appraisal of urban aquatic chemical mixture exposures. Future consideration is also needed of the role of nonchemical stressors in such highly modified urban water bodies. Environ Toxicol Chem 2018;37:703-714. © 2017 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.