Publications by category
Books
Tyler CR, Parsons A, Rogers NJ, Lange A, Brown AR (2019).
Plasticisers and Their Impact on Wildlife.Abstract:
Plasticisers and Their Impact on Wildlife
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Journal articles
Brown AR (In Press). Predicting the effects of endocrine disruptors on fish populations. Human and ecological risk assessment, 9, 761-788.
Brown A, Webber J, Zonneveld S, Carless D, Jackson B, Artioli Y, Miller P, Holmyard J, Baker-Austin C, Kershaw S, et al (In Press). Stakeholder perspectives on the importance of water quality and other constraints for sustainable mariculture.
Environmental Science and Policy, 1-37.
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Maltby L, Brown R, Faber JH, Galic N, Van den Brink PJ, Warwick O, Marshall S (2021). Assessing chemical risk within an ecosystem services framework: Implementation and added value. Science of the Total Environment, 791, 148631-148631.
Brown AR, Marshall S, Cooper C, Whitehouse P, Van den Brink PJ, Faber JH, Maltby L (2021). Assessing the feasibility and value of employing an ecosystem services approach in chemical environmental risk assessment under the Water Framework Directive. Science of the Total Environment, 789, 147857-147857.
Faber JH, Marshall S, Brown AR, Holt A, van den Brink PJ, Maltby L (2021). Identifying ecological production functions for use in ecosystem services-based environmental risk assessment of chemicals.
Sci Total Environ,
791Abstract:
Identifying ecological production functions for use in ecosystem services-based environmental risk assessment of chemicals.
There is increasing research interest in the application of the ecosystem services (ES) concept in the environmental risk assessment of chemicals to support formulating and operationalising regulatory environmental protection goals and making environmental risk assessment more policy- and value-relevant. This requires connecting ecosystem structure and processes to ecosystem function and henceforth to provision of ecosystem goods and services and their economic valuation. Ecological production functions (EPFs) may help to quantify these connections in a transparent manner and to predict ES provision based on function-related descriptors for service providing species, communities, ecosystems or habitats. We review scientific literature for EPFs to evaluate availability across provisioning and regulation and maintenance services (CICES v5.1 classification). We found quantitative production functions for nearly all ES, often complemented with economic valuation of physical or monetary flows. We studied the service providing units in these EPFs to evaluate the potential for extrapolation of toxicity data for test species obtained from standardised testing to ES provision. A broad taxonomic representation of service providers was established, but quantitative models directly linking standard test species to ES provision were extremely scarce. A pragmatic way to deal with this data gap would be the use of proxies for related taxa and stepwise functional extrapolation to ES provision and valuation, which we conclude possible for most ES. We suggest that EPFs may be used in defining specific protection goals (SPGs), and illustrate, using pollination as an example, the availability of information for the ecological entity and attribute dimensions of SPGs. Twenty-five pollination EPFs were compiled from the literature for biological entities ranging from 'colony' to 'habitat', with 75% referring to 'functional group'. With about equal representation of the attributes 'function', 'abundance' and 'diversity', SPGs for pollination therefore would seem best substantiated by EPFs at the level of functional group.
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Van den Brink PJ, Alix A, Thorbek P, Baveco H, Agatz A, Faber JH, Brown AR, Marshall S, Maltby L (2021). The use of ecological models to assess the effects of a plant protection product on ecosystem services provided by an orchard. Science of the Total Environment, 798, 149329-149329.
Mintram KS, Maynard SK, Brown AR, Boyd R, Johnston ASA, Sibly RM, Thorbek P, Tyler CR (2020). Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.
Aquat Toxicol,
224Abstract:
Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.
The potential environmental impacts of chemical exposures on wildlife are of growing concern. Freshwater ecosystems are vulnerable to chemical effects and wildlife populations, including fish, can be exposed to concentrations known to cause adverse effects at the individual level. Wild fish populations are also often subjected to numerous other stressors simultaneously which in temperate climates often include sustained periods of food limitation. The potential interactive effects of chemical exposures and food limitation on fish populations are however difficult to establish in the field. Mechanistic modelling approaches can be employed to help predict how the physiological effects of chemicals and food limitation on individuals may translate to population-level effects. Here an energy budget-individual-based model was developed and the control (no chemical) model was validated for the three-spined stickleback. Findings from two endocrine active chemical (EAC) case studies, (ethinyloestradiol and trenbolone) were then used to investigate how effects on individual fecundity translated into predicted population-level effects for environmentally relevant exposures. The cumulative effects of chemical exposure and food limitation were included in these analyses. Results show that effects of each EAC on the population were dependent on energy availability, and effects on population abundance were exacerbated by food limitation. Findings suggest that chemical effects and density dependent food competition interact to determine population responses to chemical exposures. Our study illustrates how mechanistic modelling approaches might usefully be applied to account for specific chemical effects, energy budgets and density-dependent competition, to provide a more integrated evaluation of population outcomes in chemical risk assessments.
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Brown A, Lowe C, Shutler J, Tyler C, Lilley M (2019). Assessing risks and mitigating impacts of Harmful Algal Blooms on mariculture and marine fisheries.
Reviews in Aquaculture, 1-77.
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Mintram KS, Brown AR, Maynard SK, Liu C, Parker SJ, Tyler CR, Thorbek P (2018). Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback.
Ecological Modelling,
387, 107-117.
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Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback
The effects of toxicant exposure on individuals captured in standard environmental risk assessments (ERA) do not necessarily translate proportionally into effects at the population-level. Population models can incorporate population resilience, physiological susceptibility, and likelihood of exposure, and can therefore be employed to extrapolate from individual- to population-level effects in ERA. Here, we present the development of an individual-based model (IBM) for the three-spined stickleback (Gasterosteus aculeatus) and its application in assessing population-level effects of disrupted male breeding behaviour after exposure to the anti-androgenic pesticide, fenitrothion. The stickleback is abundant in marine, brackish, and freshwater systems throughout Europe and their complex breeding strategy makes wild populations potentially vulnerable to the effects of endocrine disrupting chemicals (EDCs). Modelled population dynamics matched those of a UK field population and the IBM is therefore considered to be representative of a natural population. Literature derived dose-response relationships of fenitrothion-induced disruption of male breeding behaviours were applied in the IBM to assess population-level impacts. The modelled population was exposed to fenitrothion under both continuous (worst-case) and intermittent (realistic) exposure patterns and population recovery was assessed. The results suggest that disruption of male breeding behaviours at the individual-level cause impacts on population abundance under both fenitrothion exposure regimes; however, density-dependent processes can compensate for some of these effects, particularly for an intermittent exposure scenario. Our findings further demonstrate the importance of understanding life-history traits, including reproductive strategies and behaviours, and their density-dependence, when assessing the potential population-level risks of EDCs.
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Mintram KS, Brown AR, Maynard SK, Thorbek P, Tyler CR (2018). Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish.
Crit Rev Toxicol,
48(2), 109-120.
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Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish.
Endocrine active chemicals (EACs) are widespread in freshwater environments and both laboratory and field based studies have shown reproductive effects in fish at environmentally relevant exposures. Environmental risk assessment (ERA) seeks to protect wildlife populations and prospective assessments rely on extrapolation from individual-level effects established for laboratory fish species to populations of wild fish using arbitrary safety factors. Population susceptibility to chemical effects, however, depends on exposure risk, physiological susceptibility, and population resilience, each of which can differ widely between fish species. Population models have significant potential to address these shortfalls and to include individual variability relating to life-history traits, demographic and density-dependent vital rates, and behaviors which arise from inter-organism and organism-environment interactions. Confidence in population models has recently resulted in the EU Commission stating that results derived from reliable models may be considered when assessing the relevance of adverse effects of EACs at the population level. This review critically assesses the potential risks posed by EACs for fish populations, considers the ecological factors influencing these risks and explores the benefits and challenges of applying population modeling (including individual-based modeling) in ERA for EACs in fish. We conclude that population modeling offers a way forward for incorporating greater environmental relevance in assessing the risks of EACs for fishes and for identifying key risk factors through sensitivity analysis. Individual-based models (IBMs) allow for the incorporation of physiological and behavioral endpoints relevant to EAC exposure effects, thus capturing both direct and indirect population-level effects.
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Brown AR, Green J, Moreman J, Gunnarsson L, Mourabit S, Ball J, Winter M, Trznadel M, Correia A, Hacker C, et al (2018). Cardiovascular Effects and Molecular Mechanisms of Bisphenol a and its Metabolite MBP in Zebrafish.
Environmental Science and Technology Full text.
Green JM, Lange A, Scott A, Trznadel M, Wai HA, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR, et al (2018). Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish.
Sci Rep,
8(1).
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Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish.
Estrogen plays fundamental roles in a range of developmental processes and exposure to estrogen mimicking chemicals has been associated with various adverse health effects in both wildlife and human populations. Estrogenic chemicals are found commonly as mixtures in the environment and can have additive effects, however risk analysis is typically conducted for single-chemicals with little, or no, consideration given for an animal's exposure history. Here we developed a transgenic zebrafish with a photoconvertable fluorophore (Kaede, green to red on UV light exposure) in a skin pigment-free mutant element (ERE)-Kaede-Casper model and applied it to quantify tissue-specific fluorescence biosensor responses for combinations of estrogen exposures during early life using fluorescence microscopy and image analysis. We identify windows of tissue-specific sensitivity to ethinylestradiol (EE2) for exposure during early-life (0-5 dpf) and illustrate that exposure to estrogen (EE2) during 0-48 hpf enhances responsiveness (sensitivity) to different environmental estrogens (EE2, genistein and bisphenol A) for subsequent exposures during development. Our findings illustrate the importance of an organism's stage of development and estrogen exposure history for assessments on, and possible health risks associated with, estrogen exposure.
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Bickley LK, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (2017). Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas).
Environ Sci Technol,
51(3), 1764-1774.
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Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas).
Diclofenac is one of the most widely prescribed nonsteroidal anti-inflammatory drugs worldwide. It is frequently detected in surface waters; however, whether this pharmaceutical poses a risk to aquatic organisms is debated. Here we quantified the uptake of diclofenac by the fathead minnow (Pimephales promelas) following aqueous exposure (0.2-25.0 μg L-1) for 21 days, and evaluated the tissue and biomolecular responses in the kidney. Diclofenac accumulated in a concentration- and time-dependent manner in the plasma of exposed fish. The highest plasma concentration observed (for fish exposed to 25 μg L-1 diclofenac) was within the therapeutic range for humans. There was a strong positive correlation between exposure concentration and the number of developing nephrons observed in the posterior kidney. Diclofenac was not found to modulate the expression of genes in the kidney associated with its primary mode of action in mammals (prostaglandin-endoperoxide synthases) but modulated genes associated with kidney repair and regeneration. There were no significant adverse effects following 21 days exposure to concentrations typical of surface waters. The combination of diclofenac's uptake potential, effects on kidney nephrons and relatively small safety margin for some surface waters may warrant a longer term chronic health effects analysis for diclofenac in fish.
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Maltby L, Jackson M, Whale G, Brown AR, Hamer M, Solga A, Kabouw P, Woods R, Marshall S (2017). Is an ecosystem services-based approach developed for setting specific protection goals for plant protection products applicable to other chemicals?.
Sci Total Environ,
580, 1222-1236.
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Is an ecosystem services-based approach developed for setting specific protection goals for plant protection products applicable to other chemicals?
Clearly defined protection goals specifying what to protect, where and when, are required for designing scientifically sound risk assessments and effective risk management of chemicals. Environmental protection goals specified in EU legislation are defined in general terms, resulting in uncertainty in how to achieve them. In 2010, the European Food Safety Authority (EFSA) published a framework to identify more specific protection goals based on ecosystem services potentially affected by plant protection products. But how applicable is this framework to chemicals with different emission scenarios and receptor ecosystems? Four case studies used to address this question were: (i) oil refinery waste water exposure in estuarine environments; (ii) oil dispersant exposure in aquatic environments; (iii) down the drain chemicals exposure in a wide range of ecosystems (terrestrial and aquatic); (iv) persistent organic pollutant exposure in remote (pristine) Arctic environments. A four-step process was followed to identify ecosystems and services potentially impacted by chemical emissions and to define specific protection goals. Case studies demonstrated that, in principle, the ecosystem services concept and the EFSA framework can be applied to derive specific protection goals for a broad range of chemical exposure scenarios. By identifying key habitats and ecosystem services of concern, the approach offers the potential for greater spatial and temporal resolution, together with increased environmental relevance, in chemical risk assessments. With modifications including improved clarity on terminology/definitions and further development/refinement of the key concepts, we believe the principles of the EFSA framework could provide a methodical approach to the identification and prioritization of ecosystems, ecosystem services and the service providing units that are most at risk from chemical exposure.
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Brown AR, Whale G, Jackson M, Marshall S, Hamer M, Solga A, Kabouw P, Galay-Burgos M, Woods R, Nadzialek S, et al (2017). Toward the definition of specific protection goals for the environmental risk assessment of chemicals: a perspective on environmental regulation in Europe.
Integr Environ Assess Manag,
13(1), 17-37.
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Toward the definition of specific protection goals for the environmental risk assessment of chemicals: a perspective on environmental regulation in Europe.
This critical review examines the definition and implementation of environmental protection goals for chemicals in current European Union (EU) legislation, guidelines, and international agreements to which EU countries are party. The European chemical industry is highly regulated, and prospective environmental risk assessments (ERAs) are tailored for different classes of chemical, according to their specific hazards, uses, and environmental exposure profiles. However, environmental protection goals are often highly generic, requiring the prevention of "unacceptable" or "adverse" impacts on "biodiversity" and "ecosystems" or the "environment as a whole." This review aims to highlight working examples, challenges, solutions, and best practices for defining specific protection goals (SPGs), which are seen to be essential for refining and improving ERA. Specific protection goals hinge on discerning acceptable versus unacceptable adverse effects on the key attributes of relevant, sensitive ecological entities (ranging from organisms to ecosystems). Some isolated examples of SPGs for terrestrial and aquatic biota can be found in prospective ERA guidance for plant protection products (PPPs). However, SPGs are generally limited to environmental or nature legislation that requires environmental monitoring and retrospective ERA. This limitation is due mainly to the availability of baselines, which define acceptable versus unacceptable environmental effects on the key attributes of sentinel species, populations and/or communities, such as reproductive status, abundance, or diversity. Nevertheless, very few regulatory case examples exist in which SPGs incorporate effect magnitude, spatial extent, and temporal duration. We conclude that more holistic approaches are needed for defining SPGs, particularly with respect to protecting population sustainability, ecosystem function, and integrity, which are implicit in generic protection goals and explicit in the International Programme for Chemical Safety (IPCS) definition of "adverse effect." a possible solution, which the chemical industry is currently assessing, is wider application of the ecosystem services approach proposed by the European Food Safety Authority (EFSA) for the risk assessment of PPPs. Integr Environ Assess Manag 2017;13:17-37. © 2016 SETAC.
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Green JM, Metz J, Lee O, Trznadel M, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR (2016). High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.
Environ Sci Technol,
50(12), 6536-6545.
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High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.
Rapid embryogenesis, together with genetic similarities with mammals, and the desire to reduce mammalian testing, are major incentives for using the zebrafish model in chemical screening and testing. Transgenic zebrafish, engineered for identifying target gene expression through expression of fluorophores, have considerable potential for both high-content and high-throughput testing of chemicals for endocrine activity. Here we generated an estrogen responsive transgenic zebrafish model in a pigment-free "Casper" phenotype, facilitating identification of target tissues and quantification of these responses in whole intact fish. Using the ERE-GFP-Casper model we show chemical type and concentration dependence for green fluorescent protein (GFP) induction and both spatial and temporal responses for different environmental estrogens tested. We also developed a semiautomated (ArrayScan) imaging and image analysis system that we applied to quantify whole body fluorescence responses for a range of different estrogenic chemicals in the new transgenic zebrafish model. The zebrafish model developed provides a sensitive and highly integrative system for identifying estrogenic chemicals, their target tissues and effect concentrations for exposures in real time and across different life stages. It thus has application for chemical screening to better direct health effects analysis of environmental estrogens and for investigating the functional roles of estrogens in vertebrates.
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Wolf JC, Dietrich DR, Friederich U, Caunter J, Brown AR (2016). Qualitative and Quantitative Histomorphologic Assessment of Fathead Minnow Pimephales promelas Gonads as an Endpoint for Evaluating Endocrine-Active Compounds: a Pilot Methodology Study.
Toxicologic Pathology,
32(5), 600-612.
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Qualitative and Quantitative Histomorphologic Assessment of Fathead Minnow Pimephales promelas Gonads as an Endpoint for Evaluating Endocrine-Active Compounds: a Pilot Methodology Study
Although histopathology is routinely employed as a tool for the detection and assessment of xenobiotic-mediated effects in mammals, it is less frequently applied to fish. In part, this is due to a lack of method standardization regarding study design, tissue preservation, tissue sectioning, histopathological evaluation, reporting, and statistical analysis. The objectives of the present study were: (1) to test and refine a method for the microsurgical excision of fathead minnow (FHM) Pimephales promelas gonads for the purpose of histopathologic examination; (2) to determine the optimal combination of fixation and embedding procedures for the histopathologic and morphometric analysis of FHM gonads following exposure to a known estrogenic compound, 17 β-estradiol (E2); and (3) to provide a method for the categorization and quantification of cell types in FHM gonads by manually counting cells in digitized images using image analysis software. The light microscopic evaluation of individual gametogenic cells was greatly facilitated by specimen preparation techniques that included the excision of gonads via microdissection and by optimized fixation and embedding procedures.
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Brown AR, Owen SF, Peters J, Zhang Y, Soffker M, Paull GC, Hosken DJ, Wahab MA, Tyler CR (2015). Climate change and pollution speed declines in zebrafish populations.
Proc Natl Acad Sci U S A,
112(11), E1237-E1246.
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Climate change and pollution speed declines in zebrafish populations.
Endocrine disrupting chemicals (EDCs) are potent environmental contaminants, and their effects on wildlife populations could be exacerbated by climate change, especially in species with environmental sex determination. Endangered species may be particularly at risk because inbreeding depression and stochastic fluctuations in male and female numbers are often observed in the small populations that typify these taxa. Here, we assessed the interactive effects of water temperature and EDC exposure on sexual development and population viability of inbred and outbred zebrafish (Danio rerio). Water temperatures adopted were 28 °C (current ambient mean spawning temperature) and 33 °C (projected for the year 2100). The EDC selected was clotrimazole (at 2 μg/L and 10 μg/L), a widely used antifungal chemical that inhibits a key steroidogenic enzyme [cytochrome P450(CYP19) aromatase] required for estrogen synthesis in vertebrates. Elevated water temperature and clotrimazole exposure independently induced male-skewed sex ratios, and the effects of clotrimazole were greater at the higher temperature. Male sex ratio skews also occurred for the lower clotrimazole exposure concentration at the higher water temperature in inbred fish but not in outbred fish. Population viability analysis showed that population growth rates declined sharply in response to male skews and declines for inbred populations occurred at lower male skews than for outbred populations. These results indicate that elevated temperature associated with climate change can amplify the effects of EDCs and these effects are likely to be most acute in small, inbred populations exhibiting environmental sex determination and/or differentiation.
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Brown AR, Gunnarsson L, Kristiansson E, Tyler CR (2014). Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology.
Philosophical Transactions of the Royal Society B: Biological Sciences,
369(1656).
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Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology
© 2014 the Author(s) Published by the Royal Society. All rights reserved.Fish represent the planet’s most diverse group of vertebrates and they can be exposed to a wide range of pharmaceuticals. For practical reasons, extrapolation of pharmaceutical effects from ‘model’ species to other fish species is adopted in risk assessment. Here, we critically assess this approach. First, we show that between 65% and 86% of human drug targets are evolutionarily conserved in 12 diverse fish species. Focusing on nuclear steroid hormone receptors, we further show that the sequence of the ligand binding domain that plays a key role in drug potency is highly conserved, but there is variation between species. This variation for the oestrogen receptor, however, does not obviously account for observed differences in receptor activation. Taking the synthetic oestrogen ethinyloestradiol as a test case, and using life-table-response experiments, we demonstrate significant reductions in population growth in fathead minnow and medaka, but not zebrafish, for environmentally relevant exposures. This finding contrasts with zebrafish being ranked as more ecologically susceptible, according to two independent life-history analyses. We conclude that while most drug targets are conserved in fish, evolutionary divergence in drug-target activation, physiology, behaviour and ecological life history make it difficult to predict population-level effects. This justifies the conventional use of at least a 10× assessment factor in pharmaceutical risk assessment, to account for differences in species susceptibility.
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Arnold KE, Brown AR, Ankley GT, Sumpter JP (2014). Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES,
369(1656).
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Sumpter JP (2014). The challenge: Do pharmaceuticals present a risk to the environment, and what needs to be done to answer the question?. Environmental Toxicology and Chemistry, 33(9), 1915-1915.
Bickley LK, Brown AR, Hosken DJ, Hamilton PB, Le Page G, Paull GC, Owen SF, Tyler CR (2013). Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish.
Evolutionary Applications,
6(2), 279-289.
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Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish
Inbreeding depression is expected to be more severe in stressful environments. However, the extent to which inbreeding affects the vulnerability of populations to environmental stressors, such as chemical exposure, remains unresolved. Here we report on the combined impacts of inbreeding and exposure to an endocrine disrupting chemical (the fungicide clotrimazole) on zebrafish (Danio rerio). We show that whilst inbreeding can negatively affect reproductive traits, not all traits are affected equally. Inbreeding depression frequently only became apparent when fish were additionally stressed by chemical exposure. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring when in direct competition with outbred individuals. Levels of plasma 11-ketotestosterone, a key male sex hormone, showed substantial inbreeding depression that was unaffected by addition of the fungicide. In contrast, there was no effect of inbreeding or clotrimazole exposure on egg production. Overall, our data provide evidence that stress may amplify the effects of inbreeding on key reproductive traits, particularly those associated with male fitness. This may have important implications when considering the consequences of exposure to chemical pollutants on the fitness of wild populations. Journal compilation © 2013 Blackwell Publishing Ltd62 February 2013 10.1111/j.1752-4571.2012.00288.x Original Article Original Articles © 2012 Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution Non Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Brown AR, Bickley LK, Ryan TA, Paull GC, Hamilton PB, Owen SF, Sharpe AD, Tyler CR (2012). Differences in sexual development in inbred and outbred zebrafish (Danio rerio) and implications for chemical testing.
Aquat Toxicol,
112-113, 27-38.
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Differences in sexual development in inbred and outbred zebrafish (Danio rerio) and implications for chemical testing.
Outbred laboratory animal strains used in ecotoxicology are intended to represent wild populations. However, breeding history may vary considerably between strains, driving differences in genetic variation and phenotypes used for assessing effects of chemical exposure. We compared a range of phenotypic endpoints in zebrafish from four different "breeding treatments" comprising a Wild Indian Karyotype (WIK) zebrafish strain and a WIK/Wild strain with three levels of inbreeding (F(IT)=n, n+0.25, n+0.375) in a new Fish Sexual Development Test (FSDT). There were no differences between treatments in terms of egg viability, hatch success or fry survival. However, compared with WIKs, WIK/Wild hybrids were significantly larger in size, with more advanced gonadal (germ cell) development at the end of the test (63 days post fertilisation). Increasing the levels of inbreeding in the related WIK/Wild lines did not affect body size, but there was a significant male-bias (72%) in the most inbred line (F(IT)=n+0.375). Conversely, in the reference WIK strain there was a significant female-bias in the population (80% females). Overall, our results support the use of outbred zebrafish strains in the FSDT, where one of the core endpoints is sex ratio. Despite increased variance (and reduced statistical power) for some endpoints, WIK/Wild outbreds (F(IT)=n) met all acceptance criteria for controls in this test, whereas WIKs failed to comply with tolerance limits for sex ratio (30-70% females). Sexual development was also more advanced in WIK/Wild outbreds (cf. WIKs), providing greater scope for detection of developmental reproductive toxicity following chemical exposure.
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Brown AR, Bickley LK, Le Page G, Hosken DJ, Paull GC, Hamilton PB, Owen SF, Robinson J, Sharpe AD, Tyler CR, et al (2011). Are toxicological responses in laboratory (inbred) zebrafish representative of those in outbred (wild) populations? - a case study with an endocrine disrupting chemical.
Environ Sci Technol,
45(9), 4166-4172.
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Are toxicological responses in laboratory (inbred) zebrafish representative of those in outbred (wild) populations? - a case study with an endocrine disrupting chemical.
Laboratory animals tend to be more inbred and less genetically diverse than wild populations, and thus may differ in their susceptibility to chemical stressors. We tested this hypothesis by comparing the responses of related inbred (theoretical inbreeding F(IT) = n + 0.25) and outbred (F(IT) = n) zebrafish (Danio rerio) WIK/Wild family lines to an endocrine disrupting chemical, clotrimazole. Exposure of inbred and outbred zebrafish to 2.9 μg clotrimazole/L had no effect on survival, growth, or gonadal development. Exposure of both lines to 43.7 μg clotrimazole/L led to male-biased sex ratios compared with controls (87% versus 55% and 92% vs 64%, for inbred and outbred males, respectively), advanced germ cell development, and reduced plasma 11-ketotestosterone concentrations in males. However, outbred males (but not inbred males) developed testis that were more than twice the weight of controls, which corresponded with a proliferation of Leydig cells and maintenance of the expression (rather than down-regulation occurring in inbreds) of gonadal aromatase (cyp19a1a) and insulin-like growth factor (igf1). Our results illustrate that the effects of an endocrine disrupting chemical (clotrimazole) on some end points (here testis development) can differ between inbred and outbred zebrafish. This highlights the need for reporting pedigree/genetic information and consistency in the responses of laboratory animals (e.g. by using model compounds as positive controls).
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Langston WJ, Pope ND, Jonas PJC, Nikitic C, Field MDR, Dowell B, Shillabeer N, Swarbrick RH, Brown AR (2010). Contaminants in fine sediments and their consequences for biota of the Severn Estuary.
MARINE POLLUTION BULLETIN,
61(1-3), 68-82.
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Crane M, Gross M, Matthiessen P, Ankley GT, Axford S, Bjerregaard P, Brown R, Chapman P, Dorgeloh M, Galay-Burgos M, et al (2010). Multi-criteria decision analysis of test endpoints for detecting the effects of endocrine active substances in fish full life cycle tests. Integrated Environmental Assessment and Management, 6(3), 378-389.
Brown AR, Hosken DJ, Balloux F, Bickley LK, LePage G, Owen SF, Hetheridge MJ, Tyler CR (2009). Genetic variation, inbreeding and chemical exposure--combined effects in wildlife and critical considerations for ecotoxicology.
Philos Trans R Soc Lond B Biol Sci,
364(1534), 3377-3390.
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Genetic variation, inbreeding and chemical exposure--combined effects in wildlife and critical considerations for ecotoxicology.
Exposure to environmental chemicals can have negative consequences for wildlife and even cause localized population extinctions. Resistance to chemical stress, however, can evolve and the mechanisms include desensitized target sites, reduced chemical uptake and increased metabolic detoxification and sequestration. Chemical resistance in wildlife populations can also arise independently of exposure and may be spread by gene flow between populations. Inbreeding-matings between closely related individuals-can have negative fitness consequences for natural populations, and there is evidence of inbreeding depression in many wildlife populations. In some cases, reduced fitness in inbred populations has been shown to be exacerbated under chemical stress. In chemical testing, both inbred and outbred laboratory animals are used and for human safety assessments, iso-genic strains (virtual clones) of mice and rats are often employed that reduce response variation, the number of animals used and associated costs. In contrast, for environmental risk assessment, strains of animals are often used that have been selectively bred to maintain heterozygosity, with the assumption that they are better able to predict adverse effects in wild, genetically variable, animals. This may not necessarily be the case however, as one outbred strain may not be representative of another or of a wild population. In this paper, we critically discuss relationships between genetic variation, inbreeding and chemical effects with the intention of seeking to support more effective chemical testing for the protection of wildlife.
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Brown AR, Riddle AM, Winfield IJ, Fletcher JM, James JB (2005). Predicting the effects of endocrine disrupting chemicals on healthy and disease impacted populations of perch (perca fluviatilis). Ecological Modelling, 189(3-4), 377-395.
Cape JN, Leith ID, Binnie J, Content J, Donkin M, Skewes M, Price DN, Brown AR, Sharpe AD (2003). Effects of VOCs on herbaceous plants in an open-top chamber experiment. Environmental Pollution, 124(2), 341-353.
Warwick RM, Ashman CM, Brown AR, Clarke KR, Dowell B, Hart B, Lewis Re Shillabeer N, Somerfield PJ, Tapp JF (2002). Inter-annual changes in the biodiversity and community structure of the macrobenthos in Tees Bay and the Tees estuary, UK, associated with local and regional environmental events. Marine Ecology Progress Series, 234, 1-13.
Brown AR, Shillabeer N (1996). Development of a biologically based environmental quality standard from a long-term benthic monitoring programme in the North Sea. Oceanologica Acta, 20, 275-282.
Chapters
Brown AR, Robinson PF, Riddle AM, Panter GH (2009). Population dynamics modelling: a tool for environmental risk assessment of endocrine disrupting chemicals. In Devillers J (Ed) Endocrine disruption modelling, Boca Raton, FL, USA: CRC Press.
Cape N, Leith ID, Binnie J, Dopnkin M, Price DN, Brown AR, Schroder P (2004). Techniques for measuring the response of plants to VOC exposure. In Klump A, Ansel W, Klump G (Eds.) Urban air pollution, bioindication and environmental awareness, Göttingen: Cuvillier Verlag.
Conferences
Arnold KE, Boxall ABA, Brown AR, Cuthbert RJ, Gaw S, Hutchinson TH, Jobling S, Madden JC, Metcalfe CD, Naidoo V, et al (2013). Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems.
Abstract:
Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems
Abstract.
Publications by year
In Press
Brown AR (In Press). Predicting the effects of endocrine disruptors on fish populations. Human and ecological risk assessment, 9, 761-788.
Brown A, Webber J, Zonneveld S, Carless D, Jackson B, Artioli Y, Miller P, Holmyard J, Baker-Austin C, Kershaw S, et al (In Press). Stakeholder perspectives on the importance of water quality and other constraints for sustainable mariculture.
Environmental Science and Policy, 1-37.
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2021
Maltby L, Brown R, Faber JH, Galic N, Van den Brink PJ, Warwick O, Marshall S (2021). Assessing chemical risk within an ecosystem services framework: Implementation and added value. Science of the Total Environment, 791, 148631-148631.
Brown AR, Marshall S, Cooper C, Whitehouse P, Van den Brink PJ, Faber JH, Maltby L (2021). Assessing the feasibility and value of employing an ecosystem services approach in chemical environmental risk assessment under the Water Framework Directive. Science of the Total Environment, 789, 147857-147857.
Faber JH, Marshall S, Brown AR, Holt A, van den Brink PJ, Maltby L (2021). Identifying ecological production functions for use in ecosystem services-based environmental risk assessment of chemicals.
Sci Total Environ,
791Abstract:
Identifying ecological production functions for use in ecosystem services-based environmental risk assessment of chemicals.
There is increasing research interest in the application of the ecosystem services (ES) concept in the environmental risk assessment of chemicals to support formulating and operationalising regulatory environmental protection goals and making environmental risk assessment more policy- and value-relevant. This requires connecting ecosystem structure and processes to ecosystem function and henceforth to provision of ecosystem goods and services and their economic valuation. Ecological production functions (EPFs) may help to quantify these connections in a transparent manner and to predict ES provision based on function-related descriptors for service providing species, communities, ecosystems or habitats. We review scientific literature for EPFs to evaluate availability across provisioning and regulation and maintenance services (CICES v5.1 classification). We found quantitative production functions for nearly all ES, often complemented with economic valuation of physical or monetary flows. We studied the service providing units in these EPFs to evaluate the potential for extrapolation of toxicity data for test species obtained from standardised testing to ES provision. A broad taxonomic representation of service providers was established, but quantitative models directly linking standard test species to ES provision were extremely scarce. A pragmatic way to deal with this data gap would be the use of proxies for related taxa and stepwise functional extrapolation to ES provision and valuation, which we conclude possible for most ES. We suggest that EPFs may be used in defining specific protection goals (SPGs), and illustrate, using pollination as an example, the availability of information for the ecological entity and attribute dimensions of SPGs. Twenty-five pollination EPFs were compiled from the literature for biological entities ranging from 'colony' to 'habitat', with 75% referring to 'functional group'. With about equal representation of the attributes 'function', 'abundance' and 'diversity', SPGs for pollination therefore would seem best substantiated by EPFs at the level of functional group.
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Van den Brink PJ, Alix A, Thorbek P, Baveco H, Agatz A, Faber JH, Brown AR, Marshall S, Maltby L (2021). The use of ecological models to assess the effects of a plant protection product on ecosystem services provided by an orchard. Science of the Total Environment, 798, 149329-149329.
2020
Mintram KS, Maynard SK, Brown AR, Boyd R, Johnston ASA, Sibly RM, Thorbek P, Tyler CR (2020). Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.
Aquat Toxicol,
224Abstract:
Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.
The potential environmental impacts of chemical exposures on wildlife are of growing concern. Freshwater ecosystems are vulnerable to chemical effects and wildlife populations, including fish, can be exposed to concentrations known to cause adverse effects at the individual level. Wild fish populations are also often subjected to numerous other stressors simultaneously which in temperate climates often include sustained periods of food limitation. The potential interactive effects of chemical exposures and food limitation on fish populations are however difficult to establish in the field. Mechanistic modelling approaches can be employed to help predict how the physiological effects of chemicals and food limitation on individuals may translate to population-level effects. Here an energy budget-individual-based model was developed and the control (no chemical) model was validated for the three-spined stickleback. Findings from two endocrine active chemical (EAC) case studies, (ethinyloestradiol and trenbolone) were then used to investigate how effects on individual fecundity translated into predicted population-level effects for environmentally relevant exposures. The cumulative effects of chemical exposure and food limitation were included in these analyses. Results show that effects of each EAC on the population were dependent on energy availability, and effects on population abundance were exacerbated by food limitation. Findings suggest that chemical effects and density dependent food competition interact to determine population responses to chemical exposures. Our study illustrates how mechanistic modelling approaches might usefully be applied to account for specific chemical effects, energy budgets and density-dependent competition, to provide a more integrated evaluation of population outcomes in chemical risk assessments.
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2019
Brown A, Lowe C, Shutler J, Tyler C, Lilley M (2019). Assessing risks and mitigating impacts of Harmful Algal Blooms on mariculture and marine fisheries.
Reviews in Aquaculture, 1-77.
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Tyler CR, Parsons A, Rogers NJ, Lange A, Brown AR (2019).
Plasticisers and Their Impact on Wildlife.Abstract:
Plasticisers and Their Impact on Wildlife
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2018
Mintram KS, Brown AR, Maynard SK, Liu C, Parker SJ, Tyler CR, Thorbek P (2018). Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback.
Ecological Modelling,
387, 107-117.
Abstract:
Assessing population impacts of toxicant-induced disruption of breeding behaviours using an individual-based model for the three-spined stickleback
The effects of toxicant exposure on individuals captured in standard environmental risk assessments (ERA) do not necessarily translate proportionally into effects at the population-level. Population models can incorporate population resilience, physiological susceptibility, and likelihood of exposure, and can therefore be employed to extrapolate from individual- to population-level effects in ERA. Here, we present the development of an individual-based model (IBM) for the three-spined stickleback (Gasterosteus aculeatus) and its application in assessing population-level effects of disrupted male breeding behaviour after exposure to the anti-androgenic pesticide, fenitrothion. The stickleback is abundant in marine, brackish, and freshwater systems throughout Europe and their complex breeding strategy makes wild populations potentially vulnerable to the effects of endocrine disrupting chemicals (EDCs). Modelled population dynamics matched those of a UK field population and the IBM is therefore considered to be representative of a natural population. Literature derived dose-response relationships of fenitrothion-induced disruption of male breeding behaviours were applied in the IBM to assess population-level impacts. The modelled population was exposed to fenitrothion under both continuous (worst-case) and intermittent (realistic) exposure patterns and population recovery was assessed. The results suggest that disruption of male breeding behaviours at the individual-level cause impacts on population abundance under both fenitrothion exposure regimes; however, density-dependent processes can compensate for some of these effects, particularly for an intermittent exposure scenario. Our findings further demonstrate the importance of understanding life-history traits, including reproductive strategies and behaviours, and their density-dependence, when assessing the potential population-level risks of EDCs.
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Mintram KS, Brown AR, Maynard SK, Thorbek P, Tyler CR (2018). Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish.
Crit Rev Toxicol,
48(2), 109-120.
Abstract:
Capturing ecology in modeling approaches applied to environmental risk assessment of endocrine active chemicals in fish.
Endocrine active chemicals (EACs) are widespread in freshwater environments and both laboratory and field based studies have shown reproductive effects in fish at environmentally relevant exposures. Environmental risk assessment (ERA) seeks to protect wildlife populations and prospective assessments rely on extrapolation from individual-level effects established for laboratory fish species to populations of wild fish using arbitrary safety factors. Population susceptibility to chemical effects, however, depends on exposure risk, physiological susceptibility, and population resilience, each of which can differ widely between fish species. Population models have significant potential to address these shortfalls and to include individual variability relating to life-history traits, demographic and density-dependent vital rates, and behaviors which arise from inter-organism and organism-environment interactions. Confidence in population models has recently resulted in the EU Commission stating that results derived from reliable models may be considered when assessing the relevance of adverse effects of EACs at the population level. This review critically assesses the potential risks posed by EACs for fish populations, considers the ecological factors influencing these risks and explores the benefits and challenges of applying population modeling (including individual-based modeling) in ERA for EACs in fish. We conclude that population modeling offers a way forward for incorporating greater environmental relevance in assessing the risks of EACs for fishes and for identifying key risk factors through sensitivity analysis. Individual-based models (IBMs) allow for the incorporation of physiological and behavioral endpoints relevant to EAC exposure effects, thus capturing both direct and indirect population-level effects.
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Brown AR, Green J, Moreman J, Gunnarsson L, Mourabit S, Ball J, Winter M, Trznadel M, Correia A, Hacker C, et al (2018). Cardiovascular Effects and Molecular Mechanisms of Bisphenol a and its Metabolite MBP in Zebrafish.
Environmental Science and Technology Full text.
Green JM, Lange A, Scott A, Trznadel M, Wai HA, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR, et al (2018). Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish.
Sci Rep,
8(1).
Abstract:
Early life exposure to ethinylestradiol enhances subsequent responses to environmental estrogens measured in a novel transgenic zebrafish.
Estrogen plays fundamental roles in a range of developmental processes and exposure to estrogen mimicking chemicals has been associated with various adverse health effects in both wildlife and human populations. Estrogenic chemicals are found commonly as mixtures in the environment and can have additive effects, however risk analysis is typically conducted for single-chemicals with little, or no, consideration given for an animal's exposure history. Here we developed a transgenic zebrafish with a photoconvertable fluorophore (Kaede, green to red on UV light exposure) in a skin pigment-free mutant element (ERE)-Kaede-Casper model and applied it to quantify tissue-specific fluorescence biosensor responses for combinations of estrogen exposures during early life using fluorescence microscopy and image analysis. We identify windows of tissue-specific sensitivity to ethinylestradiol (EE2) for exposure during early-life (0-5 dpf) and illustrate that exposure to estrogen (EE2) during 0-48 hpf enhances responsiveness (sensitivity) to different environmental estrogens (EE2, genistein and bisphenol A) for subsequent exposures during development. Our findings illustrate the importance of an organism's stage of development and estrogen exposure history for assessments on, and possible health risks associated with, estrogen exposure.
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2017
Bickley LK, van Aerle R, Brown AR, Hargreaves A, Huby R, Cammack V, Jackson R, Santos EM, Tyler CR (2017). Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas).
Environ Sci Technol,
51(3), 1764-1774.
Abstract:
Bioavailability and Kidney Responses to Diclofenac in the Fathead Minnow (Pimephales promelas).
Diclofenac is one of the most widely prescribed nonsteroidal anti-inflammatory drugs worldwide. It is frequently detected in surface waters; however, whether this pharmaceutical poses a risk to aquatic organisms is debated. Here we quantified the uptake of diclofenac by the fathead minnow (Pimephales promelas) following aqueous exposure (0.2-25.0 μg L-1) for 21 days, and evaluated the tissue and biomolecular responses in the kidney. Diclofenac accumulated in a concentration- and time-dependent manner in the plasma of exposed fish. The highest plasma concentration observed (for fish exposed to 25 μg L-1 diclofenac) was within the therapeutic range for humans. There was a strong positive correlation between exposure concentration and the number of developing nephrons observed in the posterior kidney. Diclofenac was not found to modulate the expression of genes in the kidney associated with its primary mode of action in mammals (prostaglandin-endoperoxide synthases) but modulated genes associated with kidney repair and regeneration. There were no significant adverse effects following 21 days exposure to concentrations typical of surface waters. The combination of diclofenac's uptake potential, effects on kidney nephrons and relatively small safety margin for some surface waters may warrant a longer term chronic health effects analysis for diclofenac in fish.
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Maltby L, Jackson M, Whale G, Brown AR, Hamer M, Solga A, Kabouw P, Woods R, Marshall S (2017). Is an ecosystem services-based approach developed for setting specific protection goals for plant protection products applicable to other chemicals?.
Sci Total Environ,
580, 1222-1236.
Abstract:
Is an ecosystem services-based approach developed for setting specific protection goals for plant protection products applicable to other chemicals?
Clearly defined protection goals specifying what to protect, where and when, are required for designing scientifically sound risk assessments and effective risk management of chemicals. Environmental protection goals specified in EU legislation are defined in general terms, resulting in uncertainty in how to achieve them. In 2010, the European Food Safety Authority (EFSA) published a framework to identify more specific protection goals based on ecosystem services potentially affected by plant protection products. But how applicable is this framework to chemicals with different emission scenarios and receptor ecosystems? Four case studies used to address this question were: (i) oil refinery waste water exposure in estuarine environments; (ii) oil dispersant exposure in aquatic environments; (iii) down the drain chemicals exposure in a wide range of ecosystems (terrestrial and aquatic); (iv) persistent organic pollutant exposure in remote (pristine) Arctic environments. A four-step process was followed to identify ecosystems and services potentially impacted by chemical emissions and to define specific protection goals. Case studies demonstrated that, in principle, the ecosystem services concept and the EFSA framework can be applied to derive specific protection goals for a broad range of chemical exposure scenarios. By identifying key habitats and ecosystem services of concern, the approach offers the potential for greater spatial and temporal resolution, together with increased environmental relevance, in chemical risk assessments. With modifications including improved clarity on terminology/definitions and further development/refinement of the key concepts, we believe the principles of the EFSA framework could provide a methodical approach to the identification and prioritization of ecosystems, ecosystem services and the service providing units that are most at risk from chemical exposure.
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Brown AR, Whale G, Jackson M, Marshall S, Hamer M, Solga A, Kabouw P, Galay-Burgos M, Woods R, Nadzialek S, et al (2017). Toward the definition of specific protection goals for the environmental risk assessment of chemicals: a perspective on environmental regulation in Europe.
Integr Environ Assess Manag,
13(1), 17-37.
Abstract:
Toward the definition of specific protection goals for the environmental risk assessment of chemicals: a perspective on environmental regulation in Europe.
This critical review examines the definition and implementation of environmental protection goals for chemicals in current European Union (EU) legislation, guidelines, and international agreements to which EU countries are party. The European chemical industry is highly regulated, and prospective environmental risk assessments (ERAs) are tailored for different classes of chemical, according to their specific hazards, uses, and environmental exposure profiles. However, environmental protection goals are often highly generic, requiring the prevention of "unacceptable" or "adverse" impacts on "biodiversity" and "ecosystems" or the "environment as a whole." This review aims to highlight working examples, challenges, solutions, and best practices for defining specific protection goals (SPGs), which are seen to be essential for refining and improving ERA. Specific protection goals hinge on discerning acceptable versus unacceptable adverse effects on the key attributes of relevant, sensitive ecological entities (ranging from organisms to ecosystems). Some isolated examples of SPGs for terrestrial and aquatic biota can be found in prospective ERA guidance for plant protection products (PPPs). However, SPGs are generally limited to environmental or nature legislation that requires environmental monitoring and retrospective ERA. This limitation is due mainly to the availability of baselines, which define acceptable versus unacceptable environmental effects on the key attributes of sentinel species, populations and/or communities, such as reproductive status, abundance, or diversity. Nevertheless, very few regulatory case examples exist in which SPGs incorporate effect magnitude, spatial extent, and temporal duration. We conclude that more holistic approaches are needed for defining SPGs, particularly with respect to protecting population sustainability, ecosystem function, and integrity, which are implicit in generic protection goals and explicit in the International Programme for Chemical Safety (IPCS) definition of "adverse effect." a possible solution, which the chemical industry is currently assessing, is wider application of the ecosystem services approach proposed by the European Food Safety Authority (EFSA) for the risk assessment of PPPs. Integr Environ Assess Manag 2017;13:17-37. © 2016 SETAC.
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2016
Green JM, Metz J, Lee O, Trznadel M, Takesono A, Brown AR, Owen SF, Kudoh T, Tyler CR (2016). High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.
Environ Sci Technol,
50(12), 6536-6545.
Abstract:
High-Content and Semi-Automated Quantification of Responses to Estrogenic Chemicals Using a Novel Translucent Transgenic Zebrafish.
Rapid embryogenesis, together with genetic similarities with mammals, and the desire to reduce mammalian testing, are major incentives for using the zebrafish model in chemical screening and testing. Transgenic zebrafish, engineered for identifying target gene expression through expression of fluorophores, have considerable potential for both high-content and high-throughput testing of chemicals for endocrine activity. Here we generated an estrogen responsive transgenic zebrafish model in a pigment-free "Casper" phenotype, facilitating identification of target tissues and quantification of these responses in whole intact fish. Using the ERE-GFP-Casper model we show chemical type and concentration dependence for green fluorescent protein (GFP) induction and both spatial and temporal responses for different environmental estrogens tested. We also developed a semiautomated (ArrayScan) imaging and image analysis system that we applied to quantify whole body fluorescence responses for a range of different estrogenic chemicals in the new transgenic zebrafish model. The zebrafish model developed provides a sensitive and highly integrative system for identifying estrogenic chemicals, their target tissues and effect concentrations for exposures in real time and across different life stages. It thus has application for chemical screening to better direct health effects analysis of environmental estrogens and for investigating the functional roles of estrogens in vertebrates.
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Wolf JC, Dietrich DR, Friederich U, Caunter J, Brown AR (2016). Qualitative and Quantitative Histomorphologic Assessment of Fathead Minnow Pimephales promelas Gonads as an Endpoint for Evaluating Endocrine-Active Compounds: a Pilot Methodology Study.
Toxicologic Pathology,
32(5), 600-612.
Abstract:
Qualitative and Quantitative Histomorphologic Assessment of Fathead Minnow Pimephales promelas Gonads as an Endpoint for Evaluating Endocrine-Active Compounds: a Pilot Methodology Study
Although histopathology is routinely employed as a tool for the detection and assessment of xenobiotic-mediated effects in mammals, it is less frequently applied to fish. In part, this is due to a lack of method standardization regarding study design, tissue preservation, tissue sectioning, histopathological evaluation, reporting, and statistical analysis. The objectives of the present study were: (1) to test and refine a method for the microsurgical excision of fathead minnow (FHM) Pimephales promelas gonads for the purpose of histopathologic examination; (2) to determine the optimal combination of fixation and embedding procedures for the histopathologic and morphometric analysis of FHM gonads following exposure to a known estrogenic compound, 17 β-estradiol (E2); and (3) to provide a method for the categorization and quantification of cell types in FHM gonads by manually counting cells in digitized images using image analysis software. The light microscopic evaluation of individual gametogenic cells was greatly facilitated by specimen preparation techniques that included the excision of gonads via microdissection and by optimized fixation and embedding procedures.
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2015
Brown AR, Owen SF, Peters J, Zhang Y, Soffker M, Paull GC, Hosken DJ, Wahab MA, Tyler CR (2015). Climate change and pollution speed declines in zebrafish populations.
Proc Natl Acad Sci U S A,
112(11), E1237-E1246.
Abstract:
Climate change and pollution speed declines in zebrafish populations.
Endocrine disrupting chemicals (EDCs) are potent environmental contaminants, and their effects on wildlife populations could be exacerbated by climate change, especially in species with environmental sex determination. Endangered species may be particularly at risk because inbreeding depression and stochastic fluctuations in male and female numbers are often observed in the small populations that typify these taxa. Here, we assessed the interactive effects of water temperature and EDC exposure on sexual development and population viability of inbred and outbred zebrafish (Danio rerio). Water temperatures adopted were 28 °C (current ambient mean spawning temperature) and 33 °C (projected for the year 2100). The EDC selected was clotrimazole (at 2 μg/L and 10 μg/L), a widely used antifungal chemical that inhibits a key steroidogenic enzyme [cytochrome P450(CYP19) aromatase] required for estrogen synthesis in vertebrates. Elevated water temperature and clotrimazole exposure independently induced male-skewed sex ratios, and the effects of clotrimazole were greater at the higher temperature. Male sex ratio skews also occurred for the lower clotrimazole exposure concentration at the higher water temperature in inbred fish but not in outbred fish. Population viability analysis showed that population growth rates declined sharply in response to male skews and declines for inbred populations occurred at lower male skews than for outbred populations. These results indicate that elevated temperature associated with climate change can amplify the effects of EDCs and these effects are likely to be most acute in small, inbred populations exhibiting environmental sex determination and/or differentiation.
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2014
Brown AR, Gunnarsson L, Kristiansson E, Tyler CR (2014). Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology.
Philosophical Transactions of the Royal Society B: Biological Sciences,
369(1656).
Abstract:
Assessing variation in the potential susceptibility of fish to pharmaceuticals, considering evolutionary differences in their physiology and ecology
© 2014 the Author(s) Published by the Royal Society. All rights reserved.Fish represent the planet’s most diverse group of vertebrates and they can be exposed to a wide range of pharmaceuticals. For practical reasons, extrapolation of pharmaceutical effects from ‘model’ species to other fish species is adopted in risk assessment. Here, we critically assess this approach. First, we show that between 65% and 86% of human drug targets are evolutionarily conserved in 12 diverse fish species. Focusing on nuclear steroid hormone receptors, we further show that the sequence of the ligand binding domain that plays a key role in drug potency is highly conserved, but there is variation between species. This variation for the oestrogen receptor, however, does not obviously account for observed differences in receptor activation. Taking the synthetic oestrogen ethinyloestradiol as a test case, and using life-table-response experiments, we demonstrate significant reductions in population growth in fathead minnow and medaka, but not zebrafish, for environmentally relevant exposures. This finding contrasts with zebrafish being ranked as more ecologically susceptible, according to two independent life-history analyses. We conclude that while most drug targets are conserved in fish, evolutionary divergence in drug-target activation, physiology, behaviour and ecological life history make it difficult to predict population-level effects. This justifies the conventional use of at least a 10× assessment factor in pharmaceutical risk assessment, to account for differences in species susceptibility.
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Arnold KE, Brown AR, Ankley GT, Sumpter JP (2014). Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES,
369(1656).
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Sumpter JP (2014). The challenge: Do pharmaceuticals present a risk to the environment, and what needs to be done to answer the question?. Environmental Toxicology and Chemistry, 33(9), 1915-1915.
2013
Arnold KE, Boxall ABA, Brown AR, Cuthbert RJ, Gaw S, Hutchinson TH, Jobling S, Madden JC, Metcalfe CD, Naidoo V, et al (2013). Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems.
Abstract:
Assessing the exposure risk and impacts of pharmaceuticals in the environment on individuals and ecosystems
Abstract.
Bickley LK, Brown AR, Hosken DJ, Hamilton PB, Le Page G, Paull GC, Owen SF, Tyler CR (2013). Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish.
Evolutionary Applications,
6(2), 279-289.
Abstract:
Interactive effects of inbreeding and endocrine disruption on reproduction in a model laboratory fish
Inbreeding depression is expected to be more severe in stressful environments. However, the extent to which inbreeding affects the vulnerability of populations to environmental stressors, such as chemical exposure, remains unresolved. Here we report on the combined impacts of inbreeding and exposure to an endocrine disrupting chemical (the fungicide clotrimazole) on zebrafish (Danio rerio). We show that whilst inbreeding can negatively affect reproductive traits, not all traits are affected equally. Inbreeding depression frequently only became apparent when fish were additionally stressed by chemical exposure. Embryo viability was significantly reduced in inbred exposed fish and there was a tendency for inbred males to sire fewer offspring when in direct competition with outbred individuals. Levels of plasma 11-ketotestosterone, a key male sex hormone, showed substantial inbreeding depression that was unaffected by addition of the fungicide. In contrast, there was no effect of inbreeding or clotrimazole exposure on egg production. Overall, our data provide evidence that stress may amplify the effects of inbreeding on key reproductive traits, particularly those associated with male fitness. This may have important implications when considering the consequences of exposure to chemical pollutants on the fitness of wild populations. Journal compilation © 2013 Blackwell Publishing Ltd62 February 2013 10.1111/j.1752-4571.2012.00288.x Original Article Original Articles © 2012 Blackwell Publishing Ltd. This is an open access article under the terms of the Creative Commons Attribution Non Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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2012
Brown AR, Bickley LK, Ryan TA, Paull GC, Hamilton PB, Owen SF, Sharpe AD, Tyler CR (2012). Differences in sexual development in inbred and outbred zebrafish (Danio rerio) and implications for chemical testing.
Aquat Toxicol,
112-113, 27-38.
Abstract:
Differences in sexual development in inbred and outbred zebrafish (Danio rerio) and implications for chemical testing.
Outbred laboratory animal strains used in ecotoxicology are intended to represent wild populations. However, breeding history may vary considerably between strains, driving differences in genetic variation and phenotypes used for assessing effects of chemical exposure. We compared a range of phenotypic endpoints in zebrafish from four different "breeding treatments" comprising a Wild Indian Karyotype (WIK) zebrafish strain and a WIK/Wild strain with three levels of inbreeding (F(IT)=n, n+0.25, n+0.375) in a new Fish Sexual Development Test (FSDT). There were no differences between treatments in terms of egg viability, hatch success or fry survival. However, compared with WIKs, WIK/Wild hybrids were significantly larger in size, with more advanced gonadal (germ cell) development at the end of the test (63 days post fertilisation). Increasing the levels of inbreeding in the related WIK/Wild lines did not affect body size, but there was a significant male-bias (72%) in the most inbred line (F(IT)=n+0.375). Conversely, in the reference WIK strain there was a significant female-bias in the population (80% females). Overall, our results support the use of outbred zebrafish strains in the FSDT, where one of the core endpoints is sex ratio. Despite increased variance (and reduced statistical power) for some endpoints, WIK/Wild outbreds (F(IT)=n) met all acceptance criteria for controls in this test, whereas WIKs failed to comply with tolerance limits for sex ratio (30-70% females). Sexual development was also more advanced in WIK/Wild outbreds (cf. WIKs), providing greater scope for detection of developmental reproductive toxicity following chemical exposure.
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2011
Brown AR, Bickley LK, Le Page G, Hosken DJ, Paull GC, Hamilton PB, Owen SF, Robinson J, Sharpe AD, Tyler CR, et al (2011). Are toxicological responses in laboratory (inbred) zebrafish representative of those in outbred (wild) populations? - a case study with an endocrine disrupting chemical.
Environ Sci Technol,
45(9), 4166-4172.
Abstract:
Are toxicological responses in laboratory (inbred) zebrafish representative of those in outbred (wild) populations? - a case study with an endocrine disrupting chemical.
Laboratory animals tend to be more inbred and less genetically diverse than wild populations, and thus may differ in their susceptibility to chemical stressors. We tested this hypothesis by comparing the responses of related inbred (theoretical inbreeding F(IT) = n + 0.25) and outbred (F(IT) = n) zebrafish (Danio rerio) WIK/Wild family lines to an endocrine disrupting chemical, clotrimazole. Exposure of inbred and outbred zebrafish to 2.9 μg clotrimazole/L had no effect on survival, growth, or gonadal development. Exposure of both lines to 43.7 μg clotrimazole/L led to male-biased sex ratios compared with controls (87% versus 55% and 92% vs 64%, for inbred and outbred males, respectively), advanced germ cell development, and reduced plasma 11-ketotestosterone concentrations in males. However, outbred males (but not inbred males) developed testis that were more than twice the weight of controls, which corresponded with a proliferation of Leydig cells and maintenance of the expression (rather than down-regulation occurring in inbreds) of gonadal aromatase (cyp19a1a) and insulin-like growth factor (igf1). Our results illustrate that the effects of an endocrine disrupting chemical (clotrimazole) on some end points (here testis development) can differ between inbred and outbred zebrafish. This highlights the need for reporting pedigree/genetic information and consistency in the responses of laboratory animals (e.g. by using model compounds as positive controls).
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2010
Langston WJ, Pope ND, Jonas PJC, Nikitic C, Field MDR, Dowell B, Shillabeer N, Swarbrick RH, Brown AR (2010). Contaminants in fine sediments and their consequences for biota of the Severn Estuary.
MARINE POLLUTION BULLETIN,
61(1-3), 68-82.
Author URL.
Crane M, Gross M, Matthiessen P, Ankley GT, Axford S, Bjerregaard P, Brown R, Chapman P, Dorgeloh M, Galay-Burgos M, et al (2010). Multi-criteria decision analysis of test endpoints for detecting the effects of endocrine active substances in fish full life cycle tests. Integrated Environmental Assessment and Management, 6(3), 378-389.
2009
Brown AR, Hosken DJ, Balloux F, Bickley LK, LePage G, Owen SF, Hetheridge MJ, Tyler CR (2009). Genetic variation, inbreeding and chemical exposure--combined effects in wildlife and critical considerations for ecotoxicology.
Philos Trans R Soc Lond B Biol Sci,
364(1534), 3377-3390.
Abstract:
Genetic variation, inbreeding and chemical exposure--combined effects in wildlife and critical considerations for ecotoxicology.
Exposure to environmental chemicals can have negative consequences for wildlife and even cause localized population extinctions. Resistance to chemical stress, however, can evolve and the mechanisms include desensitized target sites, reduced chemical uptake and increased metabolic detoxification and sequestration. Chemical resistance in wildlife populations can also arise independently of exposure and may be spread by gene flow between populations. Inbreeding-matings between closely related individuals-can have negative fitness consequences for natural populations, and there is evidence of inbreeding depression in many wildlife populations. In some cases, reduced fitness in inbred populations has been shown to be exacerbated under chemical stress. In chemical testing, both inbred and outbred laboratory animals are used and for human safety assessments, iso-genic strains (virtual clones) of mice and rats are often employed that reduce response variation, the number of animals used and associated costs. In contrast, for environmental risk assessment, strains of animals are often used that have been selectively bred to maintain heterozygosity, with the assumption that they are better able to predict adverse effects in wild, genetically variable, animals. This may not necessarily be the case however, as one outbred strain may not be representative of another or of a wild population. In this paper, we critically discuss relationships between genetic variation, inbreeding and chemical effects with the intention of seeking to support more effective chemical testing for the protection of wildlife.
Abstract.
Author URL.
Brown AR, Robinson PF, Riddle AM, Panter GH (2009). Population dynamics modelling: a tool for environmental risk assessment of endocrine disrupting chemicals. In Devillers J (Ed) Endocrine disruption modelling, Boca Raton, FL, USA: CRC Press.
2005
Brown AR, Riddle AM, Winfield IJ, Fletcher JM, James JB (2005). Predicting the effects of endocrine disrupting chemicals on healthy and disease impacted populations of perch (perca fluviatilis). Ecological Modelling, 189(3-4), 377-395.
2004
Cape N, Leith ID, Binnie J, Dopnkin M, Price DN, Brown AR, Schroder P (2004). Techniques for measuring the response of plants to VOC exposure. In Klump A, Ansel W, Klump G (Eds.) Urban air pollution, bioindication and environmental awareness, Göttingen: Cuvillier Verlag.
2003
Cape JN, Leith ID, Binnie J, Content J, Donkin M, Skewes M, Price DN, Brown AR, Sharpe AD (2003). Effects of VOCs on herbaceous plants in an open-top chamber experiment. Environmental Pollution, 124(2), 341-353.
2002
Warwick RM, Ashman CM, Brown AR, Clarke KR, Dowell B, Hart B, Lewis Re Shillabeer N, Somerfield PJ, Tapp JF (2002). Inter-annual changes in the biodiversity and community structure of the macrobenthos in Tees Bay and the Tees estuary, UK, associated with local and regional environmental events. Marine Ecology Progress Series, 234, 1-13.
1996
Brown AR, Shillabeer N (1996). Development of a biologically based environmental quality standard from a long-term benthic monitoring programme in the North Sea. Oceanologica Acta, 20, 275-282.
