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The H4IIE cell bioassay as an indicator of dioxin-like chemicals in wildlife and the environment

The H4IIE cell bioassay has proven utility as a screening tool for planar halogenated hydrocarbons (PHHs) and structurally similar chemicals accumulated in organisms from the wild. This bioassay has additional applications in hazard assessment of PHH exposed populations. In this review, the toxicological principles, current protocols, performance criteria, and field applications for the assay are described. The H4IIE cell bioassay has several advantages over the analytical measurement of PHHs in environmental samples, but conclusions from studies can be strengthened when both bioassay and analytical chemistry data are presented together. Often, the bioassay results concur with biological effects in organisms and support direct measures of PHHs. For biomonitoring purposes and prioritization of PHH-contaminated environments, the H4IIE bioassay may be faster and less expensive than analytical measurements. The H4IIE cell bioassay can be used in combination with other biomarkers such as in vivo measurements of CYP1A1 induction to help pinpoint the sources and identities of dioxin-like chemicals. The number of studies that measure H4IIE-derived TCDD-EQs continues to increase, resulting in subtle improvements over time. Further experiments are required to determine if TCDD-EQs derived from mammalian cells are adequate predictors of toxicity to non-mammalian species. The H4IIE cell bioassay has been used in over 300 published studies, and its combination of speed, simplicity, and ability to integrate the effects of complex containment mixtures makes it a valuable addition to hazard assessment and biomonitoring studies.

Critical Reviews in Toxicology

Ethoxyresorufin-O-deethylase (EROD) activity in fish as a biomarker of chemical exposure

This review compiles and evaluates existing scientific information on the use, limitations, and procedural considerations for EROD activity (a catalytic measurement of cytochrome P4501A induction) as a biomarker in fish. A multitude of chemicals induce EROD activity in a variety of fish species, the most potent inducers being structural analogs of 2,3,7,8-tetracholordibenzo- p -dioxin. Although certain chemicals may inhibit EROD induction/activity, this interference is generally not a drawback to the use of EROD induction as a biomarker. The various methods of EROD analysis currently in use yield comparable results, particularly when data are expressed as relative rates of EROD activity. EROD induction in fish is well characterized, the most important modifying factors being fish species, reproductive status and age, all of which can be controlled through proper study design. Good candidate species for biomonitoring should have a wide range between basal and induced EROD activity (e.g., common carp, channel catfish, and mummichog). EROD activity has proven value as a biomarker in a number of field investigations of bleached kraft mill and industrial effluents, contaminated sediments, and chemical spills. Research on mechanisms of CYP1A-induced toxicity suggests that EROD activity may not only indicate chemical exposure, but also may also precede effects at various levels of biological organization. A current research need is the development of chemical exposure-response relationships for EROD activity in fish. In addition, routine reporting in the literature of EROD activity in standard positive and negative control material will enhance confidence in comparing results from different studies using this biomarker.

Critical Reviews in Toxicology

Applying definitions of “asbestos” to environmental and “low-dose” exposure Levels and health effects, particularly malignant mesothelioma

Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.

Journal of Toxicology and Environmental Health, Pa

A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

The compound BMAA (β- N -methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer’s disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

Journal of Toxicology and Environmental Health, Pa

Assessment of selenium effects in lotic ecosystems

The selenium literature has grown substantially in recent years to encompass new information in a variety of areas. Correspondingly, several different approaches to establishing a new water quality criterion for selenium have been proposed since establishment of the national water quality criterion in 1987. Diverging viewpoints and interpretations of the selenium literature have lead to opposing perspectives on issues such as establishing a national criterion based on a sediment-based model, using hydrologic units to set criteria for stream reaches, and applying lentic-derived effects to lotic environments. This Commentary presents information on the lotic verse lentic controversy. Recently, an article was published that concluded that no adverse effects were occurring in a cutthroat trout population in a coldwater river with elevated selenium concentrations (C. J. Kennedy, L. E. McDonald, R. Loveridge, and M. M. Strosher, 2000, Arch. Environ. Contam. Toxicol. 39, 46–52). This article has added to the controversy rather than provided further insight into selenium toxicology. Information, or rather missing information, in the article has been critically reviewed and problems in the interpretations are discussed.

Ecotoxicology and Environmental Safety

North American osprey populations and contaminants: Historic and contemporary perspectives

Osprey ( Pandion haliaetus ) populations were adversely affected by DDT and perhaps other contaminants in the United States and elsewhere. Reduced productivity, eggshell thinning, and high DDE concentrations in eggs were the signs associated with declining osprey populations in the 1950s, 1960s, and 1970s. The species was one of the first studied on a large scale to bring contaminant issues into focus. Although few quantitative population data were available prior to the 1960s, many osprey populations in North America were studied during the 1960s and 1970s with much learned about basic life history and biology. This article reviews the historical and current effects of contaminants on regional osprey populations. Breeding populations in many regions of North America showed post-DDT-era (1972) population increases of varying magnitudes, with many populations now appearing to stabilize at much higher numbers than initially reported in the 1970s and 1980s. However, the magnitude of regional population increases in the United States between 1981 (first Nationwide Survey, ∼8,000 pairs), when some recovery had already occurred, 1994 (second survey, ∼14,200), and 2001 (third survey, ∼16,000–19,000), or any other years, is likely not a simple response to the release from earlier contaminant effects, but a response to multi-factorial effects. This indirect “contaminant effects” measurement comparing changes (i.e., recovery) in post-DDT-era population numbers over time is probably confounded by changing human attitudes toward birds of prey (shooting, destroying nests, etc.), changing habitats, changing fish populations, and perhaps competition from other species. The species' adaptation to newly created reservoirs and its increasing use of artificial nesting structures (power poles, nesting platforms, cell towers, channel markers, offshore duck blinds, etc.) are two important factors. The timing of the initial use of artificial nesting structures, which replaced declining numbers of suitable trees at many locations, varied regionally (much later in the western United States and Mexico). Because of the increasing use of artificial nesting structures, there may be more ospreys nesting in North America now than ever before. Now, with the impact of most legacy organic contaminants (DDT, other organochlorine [OC] pesticides, polychlorinated biphenyls [PCB], polychlorinated dibenzo- p -dioxins [PCDD], polychlorinated dibenzofurans (PCDF]) greatly reduced or eliminated, and some osprey populations showing evidence of stabilizing, the species was proposed as a Worldwide Sentinel Species for evaluating emerging contaminants. Several emerging contaminants are already being studied, such as polybrominated diphenyl ethers (PBDE) and perfluorinated acids and sulfonate compounds (PFC). The many advantages for continued contaminant investigations using the osprey include a good understanding of its biology and ecology, its known distribution and abundance, and its ability to habituate to humans and their activities, which permits nesting in some of the potentially most contaminated environments. It is a top predator in most ecosystems, and its nests are relatively easy to locate and study with little researcher impact on reproductive success.

Journal of Toxicology and Environmental Health, Pa

Osprey: Worldwide sentinel species for assessing and monitoring environmental contamination in rivers, lakes, reservoirs, and estuaries

In the United States, many fish and wildlife species have been used nationwide to monitor environmental contaminant exposure and effects, including carcasses of the bald eagle ( Haliaeetus leucocephalus ), the only top avian predator regularly used in the past. Unfortunately, bald eagles are sensitive to investigator intrusion at the nest. Thus, the osprey ( Pandion haliaetus ) is evaluated as a potential sentinel species for aquatic ecosystems. Several characteristics support the choice of the osprey as a sentinel species, including: (1) fish-eating diet atop the aquatic food web, (2) long-lived with strong nest fidelity, (3) adapts to human landscapes (potentially the most contaminated), (4) tolerates short-term nest disturbance, (5) nests spatially distributed at regular intervals, (6) highly visible nests easily located for study, (7) ability to accumulate most, if not all, lipophilic contaminants, (8) known sensitivity to many contaminants, and (9) nearly a worldwide distribution. These osprey traits have been instrumental in successfully using the species to understand population distribution, abundance, and changes over time; the effects of various contaminants on reproductive success; how contaminants in prey (fish on biomass basis) contribute to egg concentrations (i.e., biomagnification factors); and spatial residue patterns. Data summarized include nesting population surveys, detailed nesting studies, and chemical analyses of osprey egg, organ, blood, and feather samples for contaminants that bioaccumulate and/or biomagnify in aquatic food webs; and biochemical evaluations of blood and various organs. Studies in the United States, Canada, Mexico, Europe, and elsewhere have shown the osprey to be a useful sentinel species for monitoring selected environmental contaminants, including some emerging contaminants in lakes, reservoirs, rivers, and estuaries.

Journal of Toxicology and Environmental Health, Pa

Ecotoxicology of wild mammals

An international group of 32 scientists has critically reviewed the scientific literature on exposure and effects of environmental contaminants in wild mammals. Although the absolute number of toxicological studies in domesticated and wild mammals eclipses that for birds, a detailed examination of scientific publications and databases reveal that information for 'wild' birds is actually greater than that for 'wild' mammals. Of the various taxa of mammals, ecotoxicological data is most noticeably lacking for marsupials and monotremes. In contrast, rodents (comprising 43% of all mammal species) have been studied extensively, despite evidence of their tolerance to some organochlorine compounds, rodenticides, and even radionuclides. Mammalian species at greatest risk of exposure include those that consume a high percentage of their body weight on a daily basis (e.g., shrews, moles and bats). Aquatic mammals tend to bioaccumulate tremendous burdens of lipophilic contaminants, although storage in their fat depots may actually limit toxicity. Carnivores appear to be more sensitive to adverse effects of environmental contaminants than herbivores. Remarkably few of the thousands of compounds manufactured worldwide have been toxicologically evaluated in wild mammals, and concentrations of even fewer have been monitored in tissues. Overarching research needs include: development of new exposure/effects models and better methods for estimation of species sensitivities; generation of comparative data on contaminant bioavailability, sublethal responses and detoxication mechanisms; enhanced understanding of pesticide, industrial contaminant and metal interactions; identification of endocrine disruptive contaminants and their overall ecological significance; and finally, estimating the relative contribution of environmental contamination as a factor affecting wild mammal populations.

Society of Environmental Toxicology and Chemistry,

Moving beyond p<0.05 in ecotoxicology: A guide for practitioners

Statistical inferences play a critical role in ecotoxicology. Historically, Null Hypothesis Significance Testing (NHST) has been the dominant method for inference in ecotoxicology. As a brief and informal definition of the NHST approach, researchers compare (or test) an experimental treatment or observation against a hypothesis of no relationship or effect (the null hypothesis) using the collected data to see if the observed values are statistically significant given predefined error rates. The resulting probability of observing a value equal to or greater than the observed value assuming the null hypothesis is true is the p-value. Historically, criticisms of NHST have existed for almost a century and more recently these have grown to the point where statisticians, including the American Statistical Association, have felt the need to clarify the role of NHST and p-values in science beyond their current, common use. These limitations also exist in ecotoxicology. For example, a review of the 2010 Environmental Toxicology & Chemistry (ET&C) volume found many authors did not correctly report p-values. We repeated this review looking at the 2019 volume of ET&C and the incorrect reporting of p-values still occurred almost a decade later. Problems with NHST and p-values highlight the need for statistical inferences besides NHST, something that has long been known in ecotoxicology and the broader scientific and statistical communities. Furthermore, concerns such as these led the Executive Director of the American Statistical Association to recommend against use of statistical significance in 2019. In light of these criticisms, however, ecotoxicologists require alternative methods. In this paper, we describe some alternative methods including confidence intervals, regression analysis, dose-response curves, Bayes factors, survival analysis, and model selection. Lastly, we provide insights for what ecotoxicology might look like in a post-p-value world.

Environmental Toxicology and Chemistry

A review of extraction techniques for per- and polyfluoroalkyl substances in graminaceous plants

Per- and polyfluoroalkyl substances (PFAS) are a wide-ranging class of manufactured chemicals that are environmentally persistent. Due to their ubiquity and resistance to degradation, PFAS readily bioaccumulate in a variety of environmental matrices and elicit a range of toxicological impacts. Despite an increase in research into these compounds, there is a clear gap in consensus on extraction techniques to quantify many PFAS in certain environmental media, particularly at critical points in agricultural food systems such as pasture grasses and feedstocks. Developing methods for more comprehensive and accurate extraction of PFAS in plant tissues is crucial for the biomonitoring of PFAS contamination in these ecosystems. This review seeks to identify relevant information pertaining to the partitioning of PFAS in plant matrices and evaluate the performance of previously established methods for the extraction of PFAS in graminaceous plants. Evaluated methods varied widely in extraction techniques, limits of detection and accuracy. This review provides a framework for enhancing PFAS analysis by tailoring extraction and cleanup strategies to both complex plant matrices and diverse analyte properties. Standardizing these methodologies will provide the high-quality data essential for ecotoxicologists and policymakers to accurately map the metabolic fate and ecological risks of these pollutants across food webs.

Critical Reviews in Analytical Chemistry

A critical review on the potential impacts of neonicotinoid insecticide use: Current knowledge of environmental fate, toxicity, and implications for human health

Neonicotinoid insecticides are widely used in both urban and agricultural settings around the world. Historically, neonicotinoid insecticides have been viewed as ideal replacements for more toxic compounds, like organophosphates, due in part to their perceived limited potential to affect the environment and human health. This critical review investigates the environmental fate and toxicity of neonicotinoids and their metabolites and the potential risks associated with exposure. Neonicotinoids are found to be ubiquitous in the environment, drinking water, and food, with low-level exposure commonly documented below acceptable daily intake standards. Available toxicological data from animal studies indicate possible genotoxicity, cytotoxicity, impaired immune function, and reduced growth and reproductive success at low concentrations, while limited data from ecological or cross-sectional epidemiological studies have identified acute and chronic health effects ranging from acute respiratory, cardiovascular, and neurological symptoms to oxidative genetic damage and birth defects. Due to the heavy use of neonicotinoids and potential for cumulative chronic exposure, these insecticides represent novel risks and necessitate further study to fully understand their risks to humans.

Environmental Science: Processes and Impacts

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

Ecotoxicology of Wild Mammals

An international group of 32 scientists has critically reviewed the scientific literature on exposure and effects of environmental contaminants in wild mammals. The underlying theme of this text is encompassed by the following four questions: What exactly do we know about environmental contaminants in mammals? What are the commonalities and differences between mammal orders/species in the effects that contaminants have? How and to what degree of accuracy can we predict the adverse effects of environmental contaminants on mammalian wildlife? How significant are contaminant insults compared with other density-independent and -dependent factors such as habitat loss, climatic factors and disease? The book is organized three topical sections including introductory chapters that provide a background on environmental contaminants and the mammalian orders, eight taxonomic chapters discussing all aspects of the exposure to and effects of contaminants in mammalian orders, and four thematic chapters that review and discuss generic issues including biomarkers, prediction and extrapolation of exposure and effects, hazard and risk assessment, and the relative significance of contaminants on mammals compared with other commonly encountered stressors. A final a summary chapter identifies phylogenetic trends, critical data gaps, and overarching research needs. Although the absolute number of toxicological studies in domesticated and wild mammals eclipses that wildlife species, a detailed examination of our knowledge base reveals that information for 'wild' birds is actually greater than that for 'wild' mammals. Of the various mammalian taxa, ecotoxicological data is most noticeably lacking for marsupials and monotremes. In contrast, rodents (comprising 43% of all mammal species) have been studied extensively, despite evidence of their tolerance to some organochlorine compounds, rodenticides, and even radionuclides. Mammalian species at greatest risk of exposure include those that consume a high percentage of their body weight on a daily basis. Aquatic mammals tend to bioaccumulate tremendous burdens of lipophilic contaminants, although storage in their fat depots may actually limit toxicity. Carnivores appear to be more sensitive to adverse effects of environmental contaminants than herbivores. Remarkably few of the thousands of compounds manufactured worldwide have been toxicologically evaluated in wild mammals, and concentrations of even fewer have been monitored in tissues.

Ecological & Environmental Toxicology Series.

A critical perspective on the Society of Environmental Toxicology and Chemistry’s adherence to founding principles—Opportunities for the future

The Society of Environmental Toxicology and Chemistry (SETAC) is a global organization whose mission is the advancement of environmental science and the promotion of science-informed decision making. On SETAC’s 45th anniversary, the following question was raised: Are the 1979 founding principles of SETAC, multidisciplinary approaches to solving environmental problems, multisector engagement and scientific objectivity, still relevant to the fulfillment of its mission? In a special session held at the 45th Annual Meeting in Fort Worth, Texas, U.S., a critical evaluation of the founding principles was initiated by reviewing SETAC’s history and ongoing activities, and recommendations were made for the future. With few exceptions, participants appreciated SETAC’s purposeful efforts to approach challenging environmental issues through multisector balance, an approach that is unique amongst scientific societies. We recognized that scientists have biases and views of what they find important, regardless of employing organization, and that objectivity is best served by being aware of these biases and views. SETAC’s founding principles have stood the test of time and continue to provide a strong foundation for the Society’s mission, and with a few suggested improvements, will continue to be instrumental in guiding environmental science, stewardship and policy into the future. The significance of SETAC’s contribution of robust science grounded in reliable evidence and data was recognized as being especially crucial at this time of triple planetary crisis (climate change, pollution and biodiversity loss), compounded by rapid technological developments and geopolitical issues.

Environmental Toxicology and Chemistry

Response to Gard et al.'s (2021) Comments on the Critical Review “Polychlorinated Biphenyl Tissue-Concentration Thresholds for Survival, Growth, and Reproduction in Fish”

This response is offered to the critique by Gard et al. ( 2021 ) of our meta-analysis of polychlorinated biphenyl (PCB)-induced toxicity data in fish (Berninger and Tillitt 2019 ). Gard et al. ( 2021 ) offered numerous comments, the most substantive suggesting that 1) we should have added no-observable–adverse effect residue (NOAER) data from additional studies and all data points from selected studies, and 2) the uncertainty of aggregating data from different PCB mixtures, different species, and different life stages is too great based on a limited data set. The additional studies Gard et al. suggested either were not designed to produce toxicological data, had experimental design issues, were confounded by co-contaminants, or did not contain paired exposure–effects data and as such were not appropriate to add to the data set. Lowest-observable–adverse effect residue (LOAER) values were selected for our analysis because they represent population sensitivities from the central portions of a frequency distribution (the linear portion of dose–response curves). As a consequence, there is less uncertainty in these input data (LOAER values) and greater confidence that they accurately represent the response of fish populations tested. Modeling NOAER values is in the extrapolation portion of a dose–response relationship and subject to enhanced uncertainty. The Gard et al. ( 2021 ) critique ignores this fundamental principle of toxicology and adds/deletes data points from our data set without clear selection criteria, which artificially enhances the uncertainty of their models that ultimately are not useful. We reject the premise that it is better to use individual study data as opposed to aggregation of PCB-induced toxicity thresholds in fish.

Environmental Toxicology and Chemistry

Copper concentrations in the upper Columbia River as a limiting factor in White Sturgeon recruitment and recovery

Currently there is little natural recruitment of white sturgeon (Acipenser transmontanus) in the Upper Columbia River located in British Columbia, Canada and Washington, USA. This review of life history, physiology, and behavior of white sturgeon, along with data from recent toxicological studies, suggest that trace metals, especially Cu, affect survival and behavior of early life stage fish. Sturgeon free embryos, first feeding embryos, and mixed feeding embryos utilize interstitial spaces between gravel. Although concentrations of Cu in the water column of the Upper Columbia River are typically less than US water quality criteria defined to protect aquatic life, samples at the sediment–water interface were as large as 24 µg/L and exceed the criteria. Toxicological studies reviewed here demonstrate mortality, loss of equilibrium, and immobility at Cu concentrations of 1.5 to <16 µg/L and reduced swimming activity was documented at 0.88 to 7 μg/L. Contaminated invertebrates and slag particles provide other routes of exposure. These additional routes of exposure can cause indirect effects from starvation due to potential lack of prey items and ingestion of contaminated prey or slag particles. The lack of food in stomachs during these critical early life stages may coincide with a threshold “point of no return” at which sturgeon will be unable to survive even if food becomes available following that early time frame. These findings become especially important as work progresses to enhance white sturgeon recruitment in the Upper Columbia River. To date, decisions against including trace metals as a factor in sturgeon recovery have focused on surface‐water concentrations and measurements of lethality (LC50) to establish threshold concentrations for sturgeon sensitivity. However, information provided here suggests that measurements from the sediment–water interface and effect concentrations (EC50) be considered with white sturgeon life history characteristics. These data support minimizing Cu exposure risk to enhance a successful white sturgeon recovery effort.

Washington, British Columbia

Review of and recommendations for monitoring contaminants and their effects in the San Francisco Bay−Delta

Legacy and current-use contaminants enter into and accumulate throughout the San Francisco Bay−Delta (Bay−Delta), and are present at concentrations with known effects on species important to this diverse watershed. There remains major uncertainty and a lack of focused research able to address and provide understanding of effects across multiple biological scales, despite previous and ongoing emphasis on the need for it. These needs are challenging specifically because of the established regulatory programs that often monitor on a chemical- by-chemical basis, or in which decisions are grounded in lethality-based endpoints. To best address issues of contaminants in the Bay−Delta, monitoring efforts should consider effects of environmentally relevant mixtures and sub- lethal impacts that can affect ecosystem health. These efforts need to consider the complex environment in the Bay−Delta including variable abiotic (e.g., temperature, salinity) and biotic (e.g., pathogens) factors. This calls for controlled and focused research, and the development of a multi-disciplinary contaminant monitoring and assessment program that provides information across biological scales. Information gained in this manner will contribute toward evaluating parameters that could alleviate ecologically detrimental outcomes. This review is a result of a Special Symposium convened at the University of California−Davis (UCD) on January 31, 2017 to address critical information needed on how contaminants affect the Bay−Delta. The UCD Symposium focused on new tools and approaches for assessing multiple stressor effects to freshwater and estuarine systems. Our approach is similar to the recently proposed framework laid out by the U.S. Environmental Protection Agency (USEPA) that uses weight of evidence to scale toxicological responses to chemical contaminants in a laboratory, and to guide the conservation of priority species and habitats. As such, we also aimed to recommend multiple endpoints that could be used to promote a multi-disciplinary understanding of contaminant risks in Bay−Delta while supporting management needs.

California

Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in fish histopathology studies: a guide for investigators, authors, reviewers, and readers

Differentiating salient histopathologic changes from normal anatomic features or tissue artifacts can be decidedly challenging, especially for the novice fish pathologist. As a consequence, findings of questionable accuracy may be reported inadvertently, and the potential negative impacts of publishing inaccurate histopathologic interpretations are not always fully appreciated. The objectives of this article are to illustrate a number of specific morphologic findings in commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are frequently either misdiagnosed or underdiagnosed, and to address related issues involving the interpretation of histopathologic data. To enhance the utility of this article as a guide, photomicrographs of normal and abnormal specimens are presented. General recommendations for generating and publishing results from histopathology studies are additionally provided. It is hoped that the furnished information will be a useful resource for manuscript generation, by helping authors, reviewers, and readers to critically assess fish histopathologic data.

Toxicologic Pathology