Combined effects of pharmaceuticals, personal care products, biocides and organic contaminants on the growth of Skeletonema pseudocostatum

Organisms in the environment are exposed to a number of pollutants from different compound groups. Inaddition to the classic pollutants like the polychlorinated biphenyls, polyaromatic hydrocarbons (PAHs),alkylphenols, biocides, etc. other compound groups of concern are constantly emerging. Pharmaceuticalsand personal care products (PPCPs) can be expected to co-occur with other organic contaminants likebiocides, PAHs and alkylphenols in areas affected by wastewater, industrial effluents and intensiverecreational activity. In this study, representatives from these four different compound groups weretested individually and in mixtures in a growth inhibition assay with the marine algae Skeletonemapseudocostatum (formerly Skeletonema costatum) to determine whether the combined effects couldbe predicted by models for additive effects; the concentration addition (CA) and independent action(IA) prediction model. The eleven tested compounds reduced the growth of S. pseudocostatum in themicroplate test in a concentration-dependent manner. The order of toxicity of these chemicals wereirgarol > fluoxetine > diuron > benzo(a)pyrene > thioguanine > triclosan > propranolol > benzophenone3 > cetrimonium bromide > 4-tert-octylphenol > endosulfan. Several binary mixtures and a mixture ofeight compounds from the four different compound groups were tested. All tested mixtures wereadditive as model deviation ratios, the deviation between experimental and predicted effect concentrations, were within a factor of 2 from one or both prediction models (e.g. CA and IA). Interestingly, aconcentration dependent shift from IA to CA, potentially due to activation of similar toxicity pathwaysat higher concentrations, was observed for the mixture of eight compounds. The combined effects of themulti-compound mixture were clearly additive and it should therefore be expected that PPCPs, biocides,PAHs and alkylphenols will collectively contribute to the risk in areas contaminated by such complexmixtures.acceptedVersio

Age and Synchronization of Daphnia magna Affect Sensitivity to Teflubenzuron in Acute Standardized Toxicity Tests

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Knowledge graph embedding for ecotoxicological effect prediction

Exploring the effects of a chemical compound on a species takes a considerable experimental effort. Appropriate methods for estimating and suggesting new effects can dramatically reduce the work needed to be done by a laboratory. Here, we explore the suitability of using a knowledge graph embedding approach for ecotoxicological effect prediction. A knowledge graph has been constructed from publicly available data sets, including a species taxonomy and chemical knowledge. These knowledge sources are integrated by ontology alignment techniques. Our experimental results show that the knowledge graph and its embeddings augment the baseline models.publishedVersio

Deciphering the combined effects of environmental stressors on gene transcription : a conceptual approach

The use of classical mixture toxicity models to predict the combined effects of environmental stressors based on toxicogenomics (OMICS) data is still in its infancy. Although several studies have made attempts to implement mixture modeling in OMICS analysis to understand the low dose interactions of stressors, it is not clear how interactions occur at the molecular level and how results generated from such approaches can be better used to inform future studies and cumulative hazard assessment of multiple stressors. The present work was therefore conducted to propose a conceptual approach for combined effect assessment using global gene expression data, as illustrated by a case study on assessment of combined effects of gamma radiation and depleted uranium (DU) on Atlantic salmon (Salmo salar). Implementation of the independent action (IA) model in reanalysis of a previously published microarray gene expression dataset was performed to describe gene expression patterns of combined effects and identify key gene sets and pathways that were relevant for understanding the interactive effects of these stressors. By using this approach, 3120 differentially expressed genes (DEGs) were found to display additive effects, whereas 279 (273 synergistic, 6 antagonistic) were found to deviate from additivity. Functional analysis further revealed that multiple toxicity pathways, such as oxidative stress responses, cell cycle regulation, lipid metabolism, and immune responses were enriched by DEGs showing synergistic gene expression. A key toxicity pathway of DNA damage leading to enhanced tumorigenesis signaling is highlighted and discussed in detail as an example of how to take advantage of the approach. Furthermore, a conceptual workflow describing the integration of combined effect modeling, OMICS analysis, and bioinformatics is proposed. The present study presents a conceptual framework for utilizing OMICS data in combined effect assessment and may provide novel strategies for dealing with data analysis and interpretation of molecular responses of multiple stressors

Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation

Embargo until December 06 2018.The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49–1677 mGy/h) for 6 h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H2DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6 h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first report on changes in several chlorophyll fluorescence parameters associated with photosynthetic performance and ROS formation in microalgae after exposure to gamma radiation.acceptedVersio

Ultraviolet B modulates gamma radiation-induced stress responses in Lemna minor at multiple levels of biological organisation

Elevated levels of ionizing and non-ionizing radiation may co-occur and pose cumulative hazards to biota. However, the combined effects and underlying toxicity mechanisms of different types of radiation in aquatic plants remain poorly understood. The present study aims to demonstrate how different combined toxicity prediction approaches can collectively characterise how chronic (7 days) exposure to ultraviolet B (UVB) radiation (0.5 W m−2) modulates gamma (γ) radiation (14.9, 19.5, 43.6 mGy h−1) induced stress responses in the macrophyte Lemna minor. A suite of bioassays was applied to quantify stress responses at multiple levels of biological organisation. The combined effects (no-enhancement, additivity, synergism, antagonism) were determined by two-way analysis of variance (2 W-ANOVA) and a modified Independent Action (IA) model. The toxicological responses and the potential causality between stressors were further visualised by a network of toxicity pathways. The results showed that γ-radiation or UVB alone induced oxidative stress and programmed cell death (PCD) as well as impaired oxidative phosphorylation (OXPHOS) and photosystem II (PSII) activity in L. minor. γ-radiation also activated antioxidant responses, DNA damage repair and chlorophyll metabolism, and inhibited growth at higher dose rates (≥20 mGy h−1). When co-exposed, UVB predominantly caused non-interaction (no-enhancement or additive) effects on γ-radiation-induced antioxidant gene expression, energy quenching in PSII and growth for all dose rates, whereas antagonistic effects were observed for lipid peroxidation, OXPHOS, PCD, oxidative stress, chlorophyll metabolism and genes involved in DNA damage responses. Synergistic effects were observed for changes in photochemical quenching and non-photochemical quenching, and up-regulation of antioxidant enzyme genes (GST) at one or more dose rates, while synergistic reproductive inhibition occurred at all three γ-radiation dose rates. The present study provides mechanistic knowledge, quantitative understanding and novel analytical strategies to decipher combined effects across levels of biological organisation, which should facilitate future cumulative hazard assessments of multiple stressors.publishedVersio

Pharmaceutical pollution: Prediction of environmental concentrations from national wholesales data

The regulation and monitoring of pharmaceutical pollution in Europe lag behind that of more prominent groups. However, the repurposing of sales data to predict surface water environmental concentrations is a promising supplement to more commonly used market-based risk assessment and measurement approaches. The Norwegian Institute of Public Health (NIPH) has since the 1980s compiled the Drug Wholesale Statistics database - covering all sales of both human and veterinary pharmaceuticals to retailers, pharmacies, and healthcare providers. To date, most similar works have focused either on a small subset of Active Pharmaceutical Ingredients (APIs) or used only prescription data, often more readily available than wholesale data, but necessarily more limited. By using the NIPH’s product wholesale records, with additional information on API concentrations per product from, we have been able to calculate sales weights per year for almost 900 human and veterinary APIs for the period 2016–2019. In this paper, we present our methodology for converting the provided NIPH data from a public health to an ecotoxicological resource. From our derived dataset, we have used an equation to calculate Predicted Environmental Concentration per API for inland surface waters, a key component of environmental risk assessment. We further describe our filtering to remove ecotoxicological-exempt and data deficient APIs. Lastly, we provide a limited comparison between our dataset and similar publicly available datasets for a subset of APIs, as a validation of our approach and a demonstration of the added value of wholesale data. This dataset will provide the best coverage yet of pharmaceutical sales weights for an entire nation. Moreover, our developed routines for processing 2016–2019 data can be expanded to older Norwegian wholesales data (1974–present). Consequently, our work with this dataset can contribute to narrowing the gap between desk-based predictions of exposure from consumption, and empirical but expensive environmental measurement.publishedVersio