AOPERA: A proposed methodology and inventory of effective tools to link chemicals to adverse outcome pathways.

New approaches, like the Adverse Outcome Pathway (AOP) framework, have been developed to describe how chemicals cause toxicity by linking in vitro assays to adverse health outcomes. However, approaches, tools and resources for development of AOPs have not been well described. Here we review information resources for AOP development and define a streamlined process for linking a chemical to an existing AOP.

A modular approach for assembly of quantitative adverse outcome pathways.

The adverse outcome pathway (AOP) framework is a conceptual construct that mechanistically links molecular initiating events to adverse biological outcomes through a series of causal key events (KEs) that represent the perturbation of the biological system. Quantitative, predictive AOPs are necessary for screening emerging contaminants and potential substitutes to inform their prioritization for testing. In practice, they are not widely used because they can be costly to develop and validate.

Quantifying Wildlife and Navigation Benefits of a Dredging Beneficial-Use Project in the Lower Atchafalaya River: A Demonstration of Engineering with Nature®.

The US Army Corps of Engineers (USACE) operates and maintains numerous projects in support of its various civil works missions including flood damage risk reduction, navigation, and ecosystem restoration. Originally authorized on an economic basis, these projects may produce a broad array of unaccounted for ecosystem services (ESs) that contribute to overall human, societal, and environmental well-being. Efforts are underway to capture the full array of environmental, economic, and social impacts of these projects.

An enhanced adaptive management approach for remediation of legacy mercury in the South River.

Uncertainties about future conditions and the effects of chosen actions, as well as increasing resource scarcity, have been driving forces in the utilization of adaptive management strategies. However, many applications of adaptive management have been criticized for a number of shortcomings, including a limited ability to learn from actions and a lack of consideration of stakeholder objectives. To address these criticisms, we supplement existing adaptive management approaches with a decision-analytical approach that first informs the initial selection of management alternatives and then allows for periodic re-evaluation or phased implementation of management alternatives based on monitoring information and incorporation of stakeholder values.

Enhanced adaptive management: integrating decision analysis, scenario analysis and environmental modeling for the Everglades.

We propose to enhance existing adaptive management efforts with a decision-analytical approach that can guide the initial selection of robust restoration alternative plans and inform the need to adjust these alternatives in the course of action based on continuously acquired monitoring information and changing stakeholder values. We demonstrate an application of enhanced adaptive management for a wetland restoration case study inspired by the Florida Everglades restoration effort. We find that alternatives designed to reconstruct the pre-drainage flow may have a positive ecological impact, but may also have high operational costs and only marginally contribute to meeting other objectives such as reduction of flooding.

Variable vitellogenin response of Japanese medaka (Oryzias latipes) to weekly estrogen exposure.

Japanese medaka (Oryzias latipes) is a valuable model organism in reproductive and developmental toxicity testing. The purpose of this experiment is to assess the response of medaka to aquatic estrogen exposure over the course of 1 year. Each week, three pairs of adult male medaka were exposed separately for 4 days (100% static renewal daily) to 17beta-estradiol at a nominal level of 25 microg/l, with a fourth pair of fish exposed separately to an ethanol control.

Elevated whole brain arginine vasotocin with Aroclor 1254 exposure in two Syngnathus pipefishes.

The neurohypophysial hormone arginine vasotocin (AVT) and the neuroendocrine system strongly interact with the rest of the teleostean endocrine system. The aim of this study is to investigate the effects of exposure to an endocrine disruptor on whole brain AVT concentrations for the pipefishes Syngnathus floridae and S. fuscus.

Quantification of whole brain arginine vasotocin for two Syngnathus pipefishes: elevated concentrations correlated with paternal brooding.

Arginine vasotocin (AVT) regulates many aspects of fish physiology and behavior including courtship and reproduction. This study begins to address whether paternal functions for AVT have independently evolved in species in which paternal behavior has evolved. We quantified AVT in the brains of Syngnathus fuscus and Syngnathus floridae which, like other pipefishes and seahorses of the family Syngnathidae, brood embryos within specialized structures of the male.

Multiple stressor effects of methoprene, permethrin, and salinity on limb regeneration and molting in the mud fiddler crab (Uca pugnax).

Exposure to multiple stressors from natural and anthropogenic sources poses risk to sensitive crustacean growth and developmental processes. Applications of synthetic pyrethroids and insect growth regulators near shallow coastal waters may result in harmful mixture effects depending on the salinity regime. The potential for nonadditive effects of a permethrin (0.

Direct evidence for embryonic uptake of paternally-derived nutrients in two pipefishes (Syngnathidae: Syngnathus spp.).

Seahorses, sea dragons and pipefishes of the teleost family Syngnathidae are unique in that embryos develop within specialized brooding structures of the male. We enriched brooding Syngnathus fuscus and Syngnathus floridae males with injections of L-lysine-[(15)N(2)] and 16:0-palmitic acid 1-[(13)C] to demonstrate embryonic uptake of paternally-derived nutrients. While all embryos demonstrated amino acid enrichment, late stages showed significantly higher [(15)N], indicating greater utilization of paternal resources as yolk reserves diminished and embryonic energy demands increased.

Limb regeneration and molting processes under chronic methoprene exposure in the mud fiddler crab, Uca pugnax.

Insect growth regulator application for wetland mosquito control remains controversial due to the potential for disruption of normal development and growth processes in non-target crustaceans and beneficial arthropods, e.g. Apis mellifera.

No acute toxicity to Uca pugnax, the mud fiddler crab, following a 96-h exposure to sediment-bound permethrin.

In coastal areas, the application of pyrethroid insecticides and the resulting sediment residues pose a potential threat to marine benthic ecosystems. Pyrethroids cause acute toxicity and exhibit a wide range of sublethal effects on fish and crustaceans when exposure is aqueous. Fiddler crabs that inhabit salt marsh sediment are sensitive to sediment-associated pollutants and serve as a sentinel species for xenobiotic exposure.

Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes.

Effluents from wastewater treatment plants and untreated sewage constitute a low concentration but continuous source of pharmaceutical products to the aquatic environment. One such drug, ibuprofen, is a non-steroidal anti-inflammatory agent that primarily acts through inhibition of cyclooxygenase (COX) activity. Oryzias latipes (Japanese medaka) were exposed for 6 weeks via water to three concentrations of ibuprofen (1-100 microg/L nominal concentrations) and a water control.

Influence of persistent contaminants and steroid hormones on glioblastoma cell growth.

Glioblastoma multiforme (GBM), a malignancy characterized by its rapid progression, presents a lower risk of occurrence in women during their reproductive years. Necrosis of brain tissue during tumor invasion releases free lipids, and therefore might release contaminants stored in phospholipid-rich neuronal tissue. This study assesses the growth response of two human glioblastoma cell lines, T98G and U138-MG, treated with environmental chemicals known or likely to persist within the brain.

Influence of estuarine hypoxia on feeding and sound production by two sympatric pipefish species (Syngnathidae).

This research utilizes the acoustic behavior of two sympatric pipefish species to assess the impact of hypoxia on feeding. We collected northern, Syngnathus fuscus, and dusky pipefishes, Syngnathus floridae, from the relatively pristine Chincoteague Bay, Virginia, USA and audiovisually recorded behavior in the laboratory of fish held in normoxic (>5 mg/L O(2)) and hypoxic (2 and 1 mg/L O(2)) conditions. Both species produced high frequency ( approximately 0.

Differential parental nutrient allocation in two congeneric pipefish species (Syngnathidae: Syngnathus spp.).

Male seahorses and pipefishes of the family Syngnathidae are heralded for their unique brood pouch structures for incubating embryos. There are three general types of brood pouch with increasing complexity: simple ventral gluing, two pouch flaps and a completely sealed sac. The diversity of functional roles within a type in providing nutrition, aeration and protection to offspring is unknown.

Relationship between ethinylestradiol-mediated changes in endocrine function and reproductive impairment in Japanese medaka (Oryzias latipes).

Many biochemical endpoints currently are used to describe endocrine function in fish; however, the sensitivity of these parameters as biomarkers of impaired reproduction or sexual development is not well understood. In the present study, adult Japanese medaka (Oryzias latipes) were assessed for reproductive output and endocrine function, including circulating steroid concentrations, ex vivo steroidogenesis from the gonads, aromatase activity, hepatic estrogen receptor (ER), and plasma vitellogenin (VTG) after exposure to 0, 0.2, 5, 500, and 2,000 ng/L of 17alpha-ethinylestradiol (EE) for 14 d.

In vivo effects of black cohosh and genistein on estrogenic activity and lipid peroxidation in Japanese Medaka (Oryzias latipes).

This study was designed to assay the estrogenic activities and the antioxidant potential of ethanol extracts from the herbal dietary supplement black cohosh (Cimicifuga racemosa) relative to the natural phytoestrogen genistein. The in vivo mechanisms of action of these two natural products have not been completely elucidated, and Japanese medaka (Oryzias latipes) provides a useful organism for initial in vivo screening of natural products. While both genistein and estradiol altered ovarian and testicular steroid release and decreased circulating testosterone levels in males, neither black cohosh total extract (75-30,000 ng/fish), cimiracemoside A, 25-O-methyl-cimigenoside, actein, nor 26-deoxy-actein caused any differences in estrogenic activity compared to control fish.

Reproductive assessment of Japanese medaka (Oryzias latipes) following a four-week fluoxetine (SSRI) exposure.

The occurrence of environmental pharmaceutical products has recently received considerable attention, but impacts on the aquatic environment are largely unknown. Fluoxetine is a widely prescribed antidepressant and acts physiologically as a selective serotonin reuptake inhibitor (SSRI). To determine its potential to disrupt teleost reproductive function, Japanese medaka (Oryzias latipes) were exposed to fluoxetine at aqueous nominal concentrations of 0, 0.

Evidence of gender-and tissue-specific promoter methylation and the potential for ethinylestradiol-induced changes in Japanese medaka (Oryzias latipes) estrogen receptor and aromatase genes.

In order to explore the potential of DNA methylation to serve as a biomarker of toxicity, thus establishing a link between exposure to environmental contaminants and physiologically significant changes in gene expression, tissue- and gender-specific methylation patterns in the promoter regions of estrogen receptor (ER) and aromatase genes of Japanese medaka (Oryzias latipes) were determined. Adult male and female medaka were exposed to either 0 or 500 ng/L 17 alpha-ethinylestradiol (EE) for 14d via a waterborne exposure. Livers, gonads, and brains were removed and genomic DNA was extracted.

Effects of cadmium on the reproductive axis of Japanese medaka (Oryzias latipes).

Cadmium (Cd) is a ubquitous element and a significant inorganic pollutant that has previously been found to bioaccumulate in reproductive organs of fish and disrupt important endocrine processes, especially those involved in synthesis, release and metabolism of hormones. Clearly, there is potential for reproductive effects in fish populations exposed to Cd, however, few studies have investigated the non-lethal consequences of Cd in fish. To this extent, adult male and female Japanese medaka were exposed to 0-10 ppb Cd for 7 weeks.

Waterborne and sediment toxicity of fluoxetine to select organisms.

Ecological risk assessments of pharmaceuticals are currently difficult because little-to-no aquatic hazard and exposure information exists in the peer-reviewed literature for most therapeutics. Recently several studies have identified fluoxetine, a widely prescribed antidepressant, in municipal effluents. To evaluate the potential aquatic toxicity of fluoxetine, single species laboratory toxicity tests were performed to assess hazard to aquatic biota.

Aquatic ecotoxicology of fluoxetine.

Recent studies indicate that the pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor, is discharged in municipal wastewater treatment plant effluents to surface waters. Few data on environmental fluoxetine exposure and hazard to aquatic life are currently available in the literature. Here, we summarize information on fluoxetine detection in surface waters and review research on single-species toxicity test, Japanese medaka (Oryzias latipes) reproduction and endocrine function, and freshwater mesocosm community responses to fluoxetine exposure.

Comparison of in vitro and in vivo bioassays for estrogenicity in effluent from North American municipal wastewater facilities.

Attempts to better understand causal factors affecting estrogenicity in municipal wastewater have primarily focused on analytical evaluation of specific chemical estrogens and the use of estrogen receptor (ER) based in vitro assays. To compare analytical,in vitro, and in vivo assays for estrogenicity, wastewater from four New York and one Texas municipal wastewater facilities was evaluated for estrogenic activity using the yeast estrogen screen assay (YES) and an in vivo fish vitellogenin (VTG) assay. Estrogenic activity, as measured by the YES assay, was observed in methanol and/or methylene chloride eluents from C18 extracts in two of the New York treatment facilities and the Texas facility.