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Gerald T. Ankley

Publications and source records attributed to Gerald T. Ankley.

At least 19 recordsLinked to original sources

Per- and polyfluoroalkyl substances in surface water and sediment in Great Lakes tributaries and relations with watershed attributes

Per- and polyfluoroalkyl substances (PFAS) are chemicals of emerging concern that potentially pose risks to human and environmental health. In May–Oct 2018, sediment and passively collected surface water samples were collected from 62 tributary sites of the Laurentian Great Lakes with site catchments spanning various land cover types. Discrete samples of sediment collected manually and time-integrated surface water samples collected with polar organic chemical integrative samplers (POCIS) were analyzed for 23 and 34 PFAS, respectively. Concentrations of individual PFAS in sediment and surface water varied immensely among sites from below detection to 20,800 ng kg −1 and 247 ng L −1 , respectively. Of all target compounds, PFOS was the most frequently detected in sediment (56 of 62 sites) and had the highest median concentration (132 ng kg −1 ). PFOA, PFHxS, PFOS, PFHpA, and PFNA (full chemical names are listed in online supplementary material Table S2) were detected in all 60 surface water sites, with median estimated concentrations of 5.9, 5.2, 4.6, 3.7, and 1.3 ng L −1 , respectively. Compounds with 8–13 fluorinated carbons comprised a larger proportion of sediment PFAS than compounds with 4–7 fluorinated carbons, whereas compounds with 4–7 fluorinated carbons comprised a greater proportion of PFAS in surface waters. Watershed attributes, including urban land cover, airports per catchment area, and wastewater treatment plants flow percentage were significantly ( p < 0.05) and positively related with PFAS sum concentrations in sediment and (or) surface water. Collectively, these results, albeit with some uncertainty in the estimated concentrations, highlight the relation PFAS occurrence has with human activities and documents widespread low-level PFAS contamination across the Great Lakes basin.

Great Lakes

Potential for biological effects of per- and polyfluoroalkyl substances in Great Lakes tributaries and associations with land cover and wastewater effluent

Surface water concentrations of per- and polyfluoroalkyl substances (PFAS) and potential for resulting biological effects were estimated in a study using polar organic chemical integrative samplers (POCIS) from 60 tributary sites within 20 watersheds in the Great Lakes Basin in 2018. Sites represented a range of urban to agricultural, forested, and wetland land uses and included a gradient of wastewater treatment effluent from zero to 44% of annual streamflow. Several sites also had airport influence. Twenty-one of 32 targeted PFAS compounds were detected in POCIS samplers, of which, 16 had available POCIS sampling rates, enabling time-weighted water concentration estimates and comparison with available effects data. Estimated water concentrations were compared with published water quality guidelines (available for nine PFAS), effect concentrations reported in primary literature within the ECOTOX Knowledgebase for apical endpoints (10 PFAS) and nonapical endpoints (10 PFAS), and in vitro high-throughput screening data from the U.S. Environmental Protection Agency Toxicity Forecaster (ToxCast; 14 PFAS). Based on a conservative evaluation approach that was also weighted for persistence and limitations in available toxicological information, five individual PFAS, including perfluorooctanesulfonic acid, perfluorohexanesulfonic acid, perfluorobutanesulfonic acid, perfluorooctanoic acid, and perfluorononanoic acid were identified as warranting additional investigation. Possible increased potency of PFAS mixtures over individual chemical effects, estimated by summation of exposure-activity ratios (EARs) for chemicals that influence common ToxCast assays and specified gene targets, indicated that EAR values increased up to 5.6-fold over individual chemicals, with up to 14 chemicals contributing to mixture effect predictions. Potential for biological effects from PFAS, as estimated by summed exposure-activity ratios, were correlated with urban land use and the proportion of streamflow contributed by wastewater effluent.

Great Lakes tributaries

Potential hazards of polycyclic aromatic hydrocarbons in Great Lakes tributaries using water column and porewater passive samplers and sediment wquilibrium partitioning

The potential for polycyclic aromatic hydrocarbon (PAH)-related effects in benthic organisms is commonly estimated from organic carbon-normalized sediment concentrations based on equilibrium partitioning (EqP). Although this approach is useful for screening purposes, it may overestimate PAH bioavailability by orders of magnitude in some sediments, leading to inflated exposure estimates and potentially unnecessary remediation costs. Recently, passive samplers have been shown to provide an accurate assessment of the freely dissolved concentrations of PAHs, and thus their bioavailability and possible biological effects, in sediment porewater and overlying surface water. We used polyethylene passive sampling devices (PEDs) to measure freely dissolved porewater and water column PAH concentrations at 55 Great Lakes (USA/Canada) tributary locations. The potential for PAH-related biological effects using PED concentrations were estimated with multiple approaches by applying EqP, water quality guidelines, and pathway-based biological activity based on in vitro bioassay results from ToxCast. Results based on the PED-based exposure estimates were compared with EqP-derived exposure estimates for concurrently collected sediment samples. The results indicate a potential overestimation of bioavailable PAH concentrations by up to 960-fold using the EqP-based method compared with measurements using PEDs. Even so, PED-based exposure estimates indicate a high potential for PAH-related biological effects at 14 locations. Our findings provide an updated, weight-of-evidence–based site prioritization to help guide possible future monitoring and mitigation efforts.

Illinois, Indiana, Michigan, Minnesota, New York,

Assessing contaminants of emerging concern in the Great Lakes Ecosystem: A decade of method development and practical application

Assessing the ecological risk of contaminants in the field typically involves consideration of a complex mixture of compounds which may or may not be detected via instrumental analyses. Further, there are insufficient data to predict the potential biological effects of many detected compounds, leading to their being characterized as contaminants of emerging concern (CECs). Over the past several years, advances in chemistry, toxicology, and bioinformatics have resulted in a variety of concepts and tools that can enhance the pragmatic assessment of the ecological risk of CECs. The present Focus article describes a 10+- year multiagency effort supported through the U.S. Great Lakes Restoration Initiative to assess the occurrence and implications of CECs in the North American Great Lakes. State-of-the-science methods and models were used to evaluate more than 700 sites in about approximately 200 tributaries across lakes Ontario, Erie, Huron, Michigan, and Superior, sometimes on multiple occasions. Studies featured measurement of up to 500 different target analytes in different environmental matrices, coupled with evaluation of biological effects in resident species, animals from in situ and laboratory exposures, and in vitro systems. Experimental taxa included birds, fish, and a variety of invertebrates, and measured endpoints ranged from molecular to apical responses. Data were integrated and evaluated using a diversity of curated knowledgebases and models with the goal of producing actionable insights for risk assessors and managers charged with evaluating and mitigating the effects of CECs in the Great Lakes. This overview is based on research and data captured in approximately about 90 peer-reviewed journal articles and reports, including approximately about 30 appearing in a virtual issue comprised of highlighted papers published in Environmental Toxicology and Chemistry or Integrated Environmental Assessment and Management . Environ Toxicol Chem 2023;42:2506–2518. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Environmental Toxicology and Chemistry

Pesticide prioritization by potential biological effects in tributaries of the Laurentian Great Lakes

Watersheds of the Great Lakes Basin (USA/Canada) are highly modified and impacted by human activities including pesticide use. Despite labeling restrictions intended to minimize risks to nontarget organisms, concerns remain that environmental exposures to pesticides may be occurring at levels negatively impacting nontarget organisms. We used a combination of organismal-level toxicity estimates (in vivo aquatic life benchmarks) and data from high-throughput screening (HTS) assays (in vitro benchmarks) to prioritize pesticides and sites of concern in streams at 16 tributaries to the Great Lakes Basin. In vivo or in vitro benchmark values were exceeded at 15 sites, 10 of which had exceedances throughout the year. Pesticides had the greatest potential biological impact at the site with the greatest proportion of agricultural land use in its basin (the Maumee River, Toledo, OH, USA), with 72 parent compounds or transformation products being detected, 47 of which exceeded at least one benchmark value. Our risk-based screening approach identified multiple pesticide parent compounds of concern in tributaries of the Great Lakes; these compounds included: eight herbicides (metolachlor, acetochlor, 2,4-dichlorophenoxyacetic acid, diuron, atrazine, alachlor, triclopyr, and simazine), three fungicides (chlorothalonil, propiconazole, and carbendazim), and four insecticides (diazinon, fipronil, imidacloprid, and clothianidin). We present methods for reducing the volume and complexity of potential biological effects data that result from combining contaminant surveillance with HTS (in vitro) and traditional (in vivo) toxicity estimates. Environ Toxicol Chem 2022;00:1–18. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Great Lakes

A framework for prioritizing contaminants in retrospective ecological assessments: Application in the Milwaukee Estuary (Milwaukee, WI)

Watersheds are subjected to diverse anthropogenic inputs, exposing aquatic biota to a wide range of chemicals. Detection of multiple, different chemicals can challenge natural resource managers who often have to determine where to allocate potentially limited resources. Here, we describe a weight-of-evidence framework for retrospectively prioritizing aquatic contaminants. To demonstrate framework utility, we used data from 96-h caged fish studies to prioritize chemicals detected in the Milwaukee Estuary (WI, USA; 2017–2018). Across study years, 77/178 targeted chemicals were detected. Chemicals were assigned prioritization scores based on spatial and temporal detection frequency, environmental distribution, environmental fate, ecotoxicological potential, and effect prediction. Chemicals were sorted into priority bins based on the intersection of prioritization score and data availability. Data-limited chemicals represented those that did not have sufficient data to adequately evaluate ecotoxicological potential or environmental fate. Seven compounds (fluoranthene, benzo[ a ]pyrene, pyrene, atrazine, metolachlor, phenanthrene, and DEET) were identified as high or medium priority and data sufficient and flagged as candidates for further effects-based monitoring studies. Twenty-one compounds were identified as high or medium priority and data limited and flagged as candidates for further ecotoxicological research. Fifteen chemicals were flagged as the lowest priority in the watershed. One of these chemicals (2-methylnaphthalene) displayed no data limitations and was flagged as a definitively low-priority chemical. The remaining chemicals displayed some data limitations and were considered lower-priority compounds (contingent on further ecotoxicological and environmental fate assessments). The remaining 34 compounds were flagged as low or medium priority. Altogether, this prioritization provided a screening-level (non-definitive) assessment that could be used to focus further resource management and risk assessment activities in the Milwaukee Estuary. Furthermore, by providing detailed methodology and a practical example with real experimental data, we demonstrated that the proposed framework represents a transparent and adaptable approach for prioritizing contaminants in freshwater environments. Integr Environ Assess Manag 2023;00:1–21. © 2022 SETAC

Wisconsin

Prioritizing pesticides of potential concern and identifying potential mixture effects in Great Lakes tributaries using passive samplers

To help meet the objectives of the Great Lakes Restoration Initiative with regard to increasing knowledge about toxic substances, 223 pesticides and pesticide transformation products were monitored in 15 Great Lakes tributaries using polar organic chemical integrative samplers. A screening-level assessment of their potential for biological effects was conducted by computing toxicity quotients (TQs) for chemicals with available US Environmental Protection Agency (USEPA) Aquatic Life Benchmark values. In addition, exposure activity ratios (EAR) were calculated using information from the USEPA ToxCast database. Between 16 and 81 chemicals were detected per site, with 97 unique compounds detected overall, for which 64 could be assessed using TQs or EARs. Ten chemicals exceeded TQ or EAR levels of concern at two or more sites. Chemicals exceeding thresholds included seven herbicides (2,4-dichlorophenoxyacetic acid, diuron, metolachlor, acetochlor, atrazine, simazine, and sulfentrazone), a transformation product (deisopropylatrazine), and two insecticides (fipronil and imidacloprid). Watersheds draining agricultural and urban areas had more detections and higher concentrations of pesticides compared with other land uses. Chemical mixtures analysis for ToxCast assays associated with common modes of action defined by gene targets and adverse outcome pathways (AOP) indicated potential activity on biological pathways related to a range of cellular processes, including xenobiotic metabolism, extracellular signaling, endocrine function, and protection against oxidative stress. Use of gene ontology databases and the AOP knowledgebase within the R-package ToxMixtures highlighted the utility of ToxCast data for identifying and evaluating potential biological effects and adverse outcomes of chemicals and mixtures. Results have provided a list of high-priority chemicals for future monitoring and potential biological effects warranting further evaluation in laboratory and field environments. Environ Toxicol Chem 2023;42:340–366. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Great Lakes tributaries

Prioritizing pharmaceutical contaminants in Great Lakes tributaries using risk-based screening techniques

In a study of 44 diverse sampling sites across 16 Great Lakes tributaries, 110 pharmaceuticals were detected of 257 monitored. The present study evaluated the ecological relevance of detected chemicals and identified heavily impacted areas to help inform resource managers and guide future investigations. Ten pharmaceuticals (caffeine, nicotine, albuterol, sulfamethoxazole, venlafaxine, acetaminophen, carbamazepine, gemfibrozil, metoprolol, and thiabendazole) were distinguished as having the greatest potential for biological effects based on comparison to screening-level benchmarks derived using information from two biological effects databases, the ECOTOX Knowledgebase and the ToxCast database. Available evidence did not suggest substantial concern for 75% of the monitored pharmaceuticals, including 147 undetected pharmaceuticals and 49 pharmaceuticals with screening-level alternative benchmarks. However, because of a lack of biological effects information, screening values were not available for 51 detected pharmaceuticals. Samples containing the greatest pharmaceutical concentrations and having the highest detection frequencies were from Lake Erie, southern Lake Michigan, and Lake Huron tributaries. Samples collected during low-flow periods had higher pharmaceutical concentrations than those collected during increased-flow periods. The wastewater-treatment plant effluent content in streams correlated positively with pharmaceutical concentrations. However, deviation from this correlation demonstrated that secondary factors, such as multiple pharmaceutical sources, were likely present at some sites. Further research could investigate high-priority pharmaceuticals as well as those for which alternative benchmarks could not be developed.

Indiana, Michigan, Minnesota, New York, Ohio, Wisc

Risk-based prioritization of organic chemicals and locations of ecological concern in sediment from Great Lakes tributaries

With improved analytical techniques, environmental monitoring studies are increasingly able to report the occurrence of tens or hundreds of chemicals per site, making it difficult to identify the most relevant chemicals from a biological standpoint. For this study, organic chemical occurrence was examined, individually and as mixtures, in the context of potential biological effects. Sediment was collected at 71 Great Lakes tributary sites and analyzed for 87 chemicals. Multiple risk-based lines of evidence were used to prioritize chemicals and locations, including comparing sediment concentrations and estimated porewater concentrations to established whole-organism benchmarks (i.e., sediment and water quality criteria and screening values) and to high-throughput toxicity screening data from the U.S. Environmental Protection Agency's ToxCast database, estimating additive effects of chemical mixtures on common ToxCast endpoints, and estimating toxic equivalencies for mixtures of alkylphenols and polycyclic aromatic hydrocarbons (PAHs). This multiple-lines-of-evidence approach enabled the screening of more chemicals, mitigated the uncertainties of individual approaches, and strengthened common conclusions. Collectively, at least one benchmark/screening value was exceeded for 54 of the 87 chemicals, with exceedances observed at all 71 of the monitoring sites. Chemicals with the greatest potential for biological effects, both individually and as mixture components, were bisphenol A, 4-nonylphenol, indole, carbazole, and several polycyclic aromatic hydrocarbons (PAHs). Potential adverse outcomes based on ToxCast gene targets and putative adverse outcome pathways relevant to individual chemicals and chemical mixtures included tumors, skewed sex ratios, reproductive dysfunction, hepatic steatosis, and early mortality, among others. Results provide a screening level prioritization of chemicals with the greatest potential for adverse biological effects and an indication of sites where they are most likely to occur.

Illinois, Indiana, Michigan, Minnesota, New York,

Exposure and effects of bioaccumulative contaminants of emerging concern in tree swallows nesting across the Laurentian Great Lakes

Contaminants of emerging concern (CECs) are a loosely defined group of chemicals whose wide-spread usage or presence in the environment has occurred more recently or for which there has been relatively little research done until recently. Many of these CECs are not currently regulated. The National Toxicology Program within the U.S. Department of Health and Human Services estimates that about 2000 CECs are introduced each year (https://ntp.niehs.nih.gov/about/). An unknown number may pose a risk to human or animal health. The Phase 1 (2010 – 2014) CEC work in birds, which is the subject of this report, assessed exposure across the Great Lakes to polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFASs), and polycyclic aromatic hydrocarbons (PAHs), and put those exposures into context with data from biologically relevant endpoints such as reproductive success, as well as, physiological response indicators (bioindicators) to assess possible effects. The group of chemicals included in Phase 1 were mainly those chemicals that bioaccumulate in tissues. Phase 2 (2015 – 2019) CEC work with tree swallows was expanded to include CECs whose occurrence in the environment is more temporary or seasonal, and that do not necessarily bioaccumulate. These are often called pseudo-persistent, because, while they are not long-lived in the environment, there are often daily inputs via waste water treatment plants, and run-off from farm fields and storm drainages, thereby making them available to biota year-round. These include pharmaceuticals, personal care products, and newer pesticides including herbicides. Tree swallow work on these less persistent CECs will be reported in the future, however see other Appendices in this report for information on some of these types of CECs (Appendices A, B, D).

Laurentian Great Lakes

Assessing the ecological risks of per‐ and polyfluoroalkyl substances: Current state‐of‐the science and a proposed path forward

Per‐ and poly‐fluoroalkyl substances (PFAS) encompass a large, heterogenous group of chemicals of potential concern to human health and the environment. Based on information for a few relatively well‐understood PFAS such as perfluorooctane sulfonate and perfluorooctanoate, there is ample basis to suspect that at least a subset can be considered persistent, bioaccumulative, and/or toxic. However, data suitable for determining risks in either prospective or retrospective assessments are lacking for the majority of PFAS. In August 2019, the Society of Environmental Toxicology and Chemistry sponsored a workshop that focused on the state‐of‐the‐science supporting risk assessment of PFAS. The present review summarizes discussions concerning the ecotoxicology and ecological risks of PFAS. First, we summarize currently available information relevant to problem formulation/prioritization, exposure, and hazard/effects of PFAS in the context of regulatory and ecological risk assessment activities from around the world. We then describe critical gaps and uncertainties relative to ecological risk assessments for PFAS and propose approaches to address these needs. Recommendations include the development of more comprehensive monitoring programs to support exposure assessment, an emphasis on research to support the formulation of predictive models for bioaccumulation, and the development of in silico, in vitro, and in vivo methods to efficiently assess biological effects for potentially sensitive species/endpoints. Addressing needs associated with assessing the ecological risk of PFAS will require cross‐disciplinary approaches that employ both conventional and new methods in an integrated, resource‐effective manner.

Environmental Toxicology and Chemistry

Toward sustainable environmental quality: Priority research questions for North America

Anticipating, identifying, and prioritizing strategic needs represent essential activities by research organizations. Decided benefits emerge when these pursuits engage globally important environment and health goals, including the United Nations Sustainable Development Goals. To this end, horizon scanning efforts can facilitate identification of specific research needs to address grand challenges. We report and discuss 40 priority research questions following engagement of scientists and engineers in North America. These timely questions identify the importance of stimulating innovation and developing new methods, tools, and concepts in environmental chemistry and toxicology to improve assessment and management of chemical contaminants and other diverse environmental stressors. Grand challenges to achieving sustainable management of the environment are becoming increasingly complex and structured by global megatrends, which collectively challenge existing sustainable environmental quality efforts. Transdisciplinary, systems‐based approaches will be required to define and avoid adverse biological effects across temporal and spatial gradients. Similarly, coordinated research activities among organizations within and among countries are necessary to address the priority research needs reported here. Acquiring answers to these 40 research questions will not be trivial, but doing so promises to advance sustainable environmental quality in the 21st century.

Environmental Toxicology and Chemistry

Potential toxicity of complex mixtures in surface waters from a nationwide survey of United States streams: Identifying in vitro bioactivities and causative chemicals

While chemical analysis of contaminant mixtures remains an essential component of environmental monitoring, bioactivity-based assessments using in vitro systems increasingly play a role in the detection of biological effects. Historically, in vitro assessments focused on a few biological pathways, e.g., aryl hydrocarbon receptor (AhR) or estrogen receptor (ER) activities. High-throughput screening (HTS) technologies have greatly increased the number of biological targets and processes that can be rapidly assessed. Here we screened extracts of surface waters from nationwide survey of United States (US) streams for bioactivities associated with 69 different endpoints using two multiplexed HTS assays. Bioactivity of extracts from 38streams was evaluated and compared with concentrations of over 700 analytes to identify chemicals contributing to observed effects. Eleven primary biological endpoints were detected. Pregnane X receptor and AhR-mediated activities were the most commonly detected. Measured chemicals did not completely account for AhR and PXR responses. Surface waters with AhR and PXR effects were associated with low intensity, developed land-cover. Likewise, elevated bioactivities frequently associated with wastewater discharges included endocrine related endpoints— ER and glucocorticoid receptor (GR). These results underscore the value of bioassay-based monitoring of environmental mixtures for detecting biological effects that could not be ascertained solely through chemical analyses.

Environmental Science & Technology

An “EAR” on environmental surveillance and monitoring: A case study on the use of Exposure–Activity Ratios (EARs) to prioritize sites, chemicals, and bioactivities of concern in Great Lakes waters

Current environmental monitoring approaches focus primarily on chemical occurrence. However, based on concentration alone, it can be difficult to identify which compounds may be of toxicological concern and should be prioritized for further monitoring, in-depth testing, or management. This can be problematic because toxicological characterization is lacking for many emerging contaminants. New sources of high-throughput screening (HTS) data, such as the ToxCast database, which contains information for over 9000 compounds screened through up to 1100 bioassays, are now available. Integrated analysis of chemical occurrence data with HTS data offers new opportunities to prioritize chemicals, sites, or biological effects for further investigation based on concentrations detected in the environment linked to relative potencies in pathway-based bioassays. As a case study, chemical occurrence data from a 2012 study in the Great Lakes Basin along with the ToxCast effects database were used to calculate exposure–activity ratios (EARs) as a prioritization tool. Technical considerations of data processing and use of the ToxCast database are presented and discussed. EAR prioritization identified multiple sites, biological pathways, and chemicals that warrant further investigation. Prioritized bioactivities from the EAR analysis were linked to discrete adverse outcome pathways to identify potential adverse outcomes and biomarkers for use in subsequent monitoring efforts.

Great Lakes

Recommended approaches to the scientific evaluation of ecotoxicological hazards and risks of endocrine-active substances

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.

Integrated Environmental Assessment and Management

Biological effects-based tools for monitoring impacted surface waters in the Great Lakes: a multiagency program in support of the Great Lakes Restoration Initiative

There is increasing demand for the implementation of effects-based monitoring and surveillance (EBMS) approaches in the Great Lakes Basin to complement traditional chemical monitoring. Herein, we describe an ongoing multiagency effort to develop and implement EBMS tools, particularly with regard to monitoring potentially toxic chemicals and assessing Areas of Concern (AOCs), as envisioned by the Great Lakes Restoration Initiative (GLRI). Our strategy includes use of both targeted and open-ended/discovery techniques, as appropriate to the amount of information available, to guide a priori end point and/or assay selection. Specifically, a combination of in vivo and in vitro tools is employed by using both wild and caged fish (in vivo), and a variety of receptor- and cell-based assays (in vitro). We employ a work flow that progressively emphasizes in vitro tools for long-term or high-intensity monitoring because of their greater practicality (e.g., lower cost, labor) and relying on in vivo assays for initial surveillance and verification. Our strategy takes advantage of the strengths of a diversity of tools, balancing the depth, breadth, and specificity of information they provide against their costs, transferability, and practicality. Finally, a series of illustrative scenarios is examined that align EBMS options with management goals to illustrate the adaptability and scaling of EBMS approaches and how they can be used in management decisions.

Great Lakes

Prior knowledge-based approach for associating contaminants with biological effects: A case study in the St. Croix River basin, MN, WI, USA

Evaluating potential adverse effects of complex chemical mixtures in the environment is challenging. One way to address that challenge is through more integrated analysis of chemical monitoring and biological effects data. In the present study, water samples from five locations near two municipal wastewater treatment plants in the St. Croix River basin, on the border of MN and WI, USA, were analyzed for 127 organic contaminants. Known chemical-gene interactions were used to develop site-specific knowledge assembly models (KAMs) and formulate hypotheses concerning possible biological effects associated with chemicals detected in water samples from each location. Additionally, hepatic gene expression data were collected for fathead minnows ( Pimephales promelas ) exposed in situ , for 12 d, at each location. Expression data from oligonucleotide microarrays were analyzed to identify functional annotation terms enriched among the differentially-expressed probes. The general nature of many of the terms made hypothesis formulation on the basis of the transcriptome-level response alone difficult. However, integrated analysis of the transcriptome data in the context of the site-specific KAMs allowed for evaluation of the likelihood of specific chemicals contributing to observed biological responses. Thirteen chemicals (atrazine, carbamazepine, metformin, thiabendazole, diazepam, cholesterol, p-cresol, phenytoin, omeprazole, ethyromycin, 17β-estradiol, cimetidine, and estrone), for which there was statistically significant concordance between occurrence at a site and expected biological response as represented in the KAM, were identified. While not definitive, the approach provides a line of evidence for evaluating potential cause-effect relationships between components of a complex mixture of contaminants and biological effects data, which can inform subsequent monitoring and investigation.

Minnesota, Wisconsin

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

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.

Integrated Environmental Assessment and Management