The field study aims to address identified research gaps by providing valuable information on the concentration, spatial distribution, pollution levels, and source apportionment of toxic and essential elements in sediment samples from four sampling sites (P1: Beira Rio (urban area), P2: Bananal (rural area), P3: Embiral (rural area), P4: Cidelândia (rural area) distributed along the middle Tocantins River, Brazil. Samples were collected in 2023 from river sections and analyzed using various contamination índices (geoaccumulation index, contamination factor, enrichment factor, pollution load index, sediment pollution index, potential ecological risk coefficients, and integrated risk index). Results indicated that the levels of aluminum, iron, manganese, and selenium exceeded legal standards in that year. Chromium, nickel, copper, zinc, and lead exceeded guidelines, mainly in section P1 for aluminum and section P3 for nickel and lead. Rainy months showed increased presence, indicating seasonal variability. The geoaccumulation index indicated low pollution levels, with lead and nickel notably present near urban and industrial areas. The enrichment factor highlighted elevated concentrations of lead and zinc in industrial areas. Both PLI and SPI indices raise concerns regarding Pb (P4) and Zn (P3) concentrations at specific times of the year. Overall, potential ecological risks were deemed low for most sites. Continuous monitoring and interventions are crucial to preserve water and environmental quality in the region.

Quantitative adverse outcome pathways (qAOPs) describe the response-response relationships that link the magnitude and/or duration of chemical interaction with a specific molecular target to the probability and/or severity of the resulting apical-level toxicity of regulatory relevance. The present study developed the first qAOP for latent toxicities showing that early life exposure adversely affects health at adulthood. Specifically, a qAOP for embryonic activation of the aryl hydrocarbon receptor 2 (AHR2) of fishes by polycyclic aromatic hydrocarbons (PAHs) leading to decreased fecundity of females at adulthood was developed by building on existing qAOPs for (1) activation of the AHR leading to early life mortality in birds and fishes, and (2) inhibition of cytochrome P450 aromatase activity leading to decreased fecundity in fishes. Using zebrafish (Danio rerio) as a model species and benzo[a]pyrene as a model PAH, three linked quantitative relationships were developed: (1) plasma estrogen in adult females as a function of embryonic exposure, (2) plasma vitellogenin in adult females as a function of plasma estrogen, and (3) fecundity of adult females as a function of plasma vitellogenin. A fourth quantitative relationship was developed for early life mortality as a function of sensitivity to activation of the AHR2 in a standardized in vitro AHR transactivation assay to integrate toxic equivalence calculations that would allow prediction of effects of exposure to untested PAHs. The accuracy of the predictions from the resulting qAOP were evaluated using experimental data from zebrafish exposed as embryos to another PAH, benzo[k]fluoranthene. The qAOP developed in the present study demonstrates the potential of the AOP framework in enabling consideration of latent toxicities in quantitative ecological risk assessments and regulatory decision-making. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

Aromatic sensitizers and related substances (SRCs), which are crucial in the paper industry for facilitating color-forming and color-developing chemical reactions, inadvertently contaminate effluents during paper recycling. Owing to their structural resemblance to endocrine-disrupting aromatic organic compounds, concerns have arisen about potential adverse effects on aquatic organisms. We focused on SRC effects via the aryl hydrocarbon receptor (AHR), employing molecular docking simulations and zebrafish (Danio rerio) embryo exposure assessments. Molecular docking revealed heightened binding affinities between certain SRCs in the paper recycling effluents and zebrafish Ahr2 and human AHR, which are pivotal components in the SRC toxicity mechanism. Fertilized zebrafish eggs were exposed to SRCs for up to 96 h post fertilization; among these substances, benzyl 2-naphthyl ether (BNE) caused morphological abnormalities, such as pericardial edema and shortened body length, at relatively low concentrations (1 μM) during embryogenesis. Gene expression of cytochrome P450 1A (cyp1a) and ahr2 was also significantly increased by BNE. Co-exposure to the AHR antagonist CH-223191 only partially mitigated BNE\'s phenotypic effects, despite the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin being relatively well restored by CH-223191, indicating BNE\'s AHR-independent toxic mechanisms. Furthermore, some SRCs, including BNE, exhibited in silico binding affinity to the estrogen receptor and upregulation of cyp19a1b gene expression. Therefore, additional insights into the toxicity of SRCs and their mechanisms are essential. The present results provide important information on SRCs and other papermaking chemicals that could help minimize the environmental impact of the paper industry. Environ Toxicol Chem 2024;00:1-13. © 2024 SETAC.

The aim of this study was to evaluate the sensitivity of the prawn Palaemon argentinus to the pyrethroid cypermethrin (CYP) and the tetramic acid spirotetramat (STM). These treatments were compared with prawns collected at a reference site to define their basal physiological state. Initially, physicochemical parameters and several pollutants at the selected site were analyzed. The LC50-96 h was determined in adult prawns. Then, prawns were exposed for 96 h to sublethal concentrations of CYP (0.0005 μg/l) and STM (0.44 mg/l) to evaluate the effects on some biochemical endpoints. A treatment combining both pesticides was also added at 5 % of these values. Controls with and without solvent (acetone) were included. The LC50-96 h values were 0.005 μg/l and 4.43 mg/l for CYP and STM, respectively. Moreover, some biomarkers linked to oxidative and energy metabolism were analyzed in the hepatopancreas and muscle of both essayed prawns and those at the basal state. The STM caused a significant decrease in total protein content (32 %) in contrast to the increase of protein carbonyl content (71 %) (p < 0.05). Also, glutathione S-transferase (52 %) and catalase (61 %) activities in the hepatopancreas of exposed prawns were higher compared to both the control and state basal groups (p < 0.05). In muscle, only a significant decrease in the lactate content (69 %) was caused by STM (p < 0.05). In addition, CYP caused a significant increase in the lactate dehydrogenase activity (110 %) in muscle and triacylglycerol content (73 %) in the hepatopancreas (p < 0.05). The integrated biomarker index (IBRv2) analysis showed that STM caused greater damage than CYP. Besides, the combined treatment showed an antagonistic interaction between both insecticides. The differential response of biomarkers to both CYP and STM exposure with respect to their basal levels shows a high sensitivity of P. argentinus demonstrating its potential role as a bioindicator organism.

There are substantial gaps in our empirical knowledge of the effects of chemical exposure on aquatic life that are unlikely to be filled by traditional laboratory toxicity testing alone. One possible alternative of generating new toxicity data is cross-species extrapolation (CSE), a statistical approach in which existing data are used to predict the effect of a chemical on untested species. Some CSE models use relatedness as a predictor of chemical sensitivity, but relatively little is known about how strongly shared evolutionary history influences sensitivity across all chemicals. To address this question, we conducted a survey of phylogenetic signal in the toxicity data from aquatic animal species for a large set of chemicals using a phylogeny inferred from taxonomy. Strong phylogenetic signal was present in just nine of thirty-six toxicity datasets, and there were no clear shared properties among those datasets with strong signal. Strong signal was rare even among chemicals specifically developed to target insects, meaning that these chemicals may be equally lethal to non-target taxa, including chordates. When signal was strong, distinct patterns of sensitivity were evident in the data, which may be informative when assembling toxicity datasets for regulatory use. Although strong signal does not appear to manifest in aquatic toxicity data for most chemicals, we encourage additional phylogenetic evaluations of toxicity data in order to guide the selection of CSE tools and as a means to explore the patterns of chemical sensitivity across the broad diversity of life.

The simultaneous or sequential application of pesticides such as triazophos (TRI) and fenvalerate (FEN) in agriculture results in their residues co-existing in the environments. However, the impact of co-exposure to TRI and FEN on the gut-liver axis, along with the underlying mechanisms, remains unclear. Our results showed that exposure to FEN (96 h-LC50 value of 0.096 mg a.i. L-1) was more toxic to adult zebrafish compared to TRI (96 h-LC50 value of 6.75 mg a.i. L-1). Furthermore, the study aimed to reveal the toxic potencies of individual and combined exposure to TRI and FEN on the liver-gut axis in zebrafish (Danio rerio). Our results also indicated that pesticide exposure decreased tight junction molecule expression and increased intestinal inflammatory molecule expression in D. rerio, with co-exposure demonstrating enhanced toxicity. Co-exposure altered gut flora structure and species abundance. RNA-Seq sequencing revealed changes in liver gene expressions, particularly enrichment of P53 signaling. Molecular docking demonstrated FEN\'s stronger binding to P53 and Caspase3, correlating with its higher toxicity. Liver pathology confirmed exacerbated liver damage by individual and co-exposures, with co-exposure inducing more severe liver injury. qPCR results showed increased pro-apoptotic gene expression and decreased anti-apoptotic gene expression, with co-exposure exhibiting an interactive effect. Overall, this study identifies specific targets and pathways influenced by these pesticides, revealing toxicity mechanisms involving the gut-liver axis, which is crucial for environmental risk assessment of pesticide mixtures.

BACKGROUND: The inappropriate use of pesticides including fungicides creates severe biological hazards that can endanger fish health and impede sustainable aquaculture.
OBJECTIVE: This study investigated the negative impacts of metiram (MET), a fungicide on the health status of Nile tilapia (Oreochromis niloticus) for a 96-hour duration as an acute exposure in a static renewal system.
METHODS: Three hundred fish (average body weight: 37.50 ± 0.22 g) were assigned into six groups (50 fish/group) with five replicates (10 fish/replicate). Fish were exposed to various six concentrations (0, 1.5, 3, 4.5, 6, and 7.5 mg/L) of MET as a water exposure to for 96-hour without water exchange. The fish\'s behavior, clinical signs, and mortalities were documented every day of the exposure period. Additionally, MET\'s impact on blood profile, stress biomarkers, hepato-renal functions, immune-antioxidant status, and brain biomarker were closely monitored.
RESULTS: The lethal concentration (LC50) of MET estimated using Finney\'s probit technique was 3.77 mg/L. The fish\'s behavior was severely impacted by acute MET exposure, as clear by an increase in surfacing, loss of equilibrium, unusual swimming, laterality, abnormal movement, and a decline in aggressive behaviors. The survivability and hematological indices (white and red blood cell count, differential white blood cell count, hematocrit value, and hemoglobin) were significantly reduced in a concentration-dependent manner following MET exposure. Acute exposure to MET (1.5-7.5 mg/L) incrementally increased stress biomarkers (nor-epinephrine, cortisol, and glucose), lipid peroxides (malondialdehyde), and brain oxidative DNA damage biomarker (8-hydroxy-2-deoxyguanosine). A hepato-renal dysfunction by MET exposure (4.5-7.5 mg/L) was evidenced by the significant increase in the alanine and aspartate aminotransferases and creatinine values. Moreover, a substantial decline in the immune parameters (lysozyme, complement 3, serum bactericidal activity, and antiprotease activity) and antioxidant variables (total antioxidant capacity, superoxide dismutase, and glutathione peroxidase) resulted from acute MET exposure.
CONCLUSIONS: According to these findings, the 96-hour LC50 of MET in Nile tilapia was 3.77 mg/L. MET exposure triggered toxicity in Nile tilapia, as seen by alterations in fish neuro-behaviors, immune-antioxidant status, hepato-renal functioning, and signifying physiological disturbances. This study emphasizes the potential ecological dangers provoked by MET as an environmental contaminant to aquatic systems. However, the long-term MET exposure is still needed to be investigated.

Pethoxamid, a member of the chloroacetamide herbicide family, is a recently approved chemical for pre- or post-emergence weed control; however, toxicity data for sublethal effects in aquatic organisms exposed to pethoxamid are non-existent in literature. To address this, we treated zebrafish embryos/larvae to pethoxamid over a 7-day period post-fertilization and evaluated several toxicological endpoints associated with oxidative stress and neurotoxicity. Continuous pethoxamid exposure did not affect survival nor hatch success in embryos/larvae for 7 days up to 1000 μg L-1. Exposure to pethoxamid did not affect embryonic ATP-linked respiration, but it did reduce non-mitochondrial respiration at the highest concentration tested. We also noted a significant increase in both apoptosis and levels of reactive oxygen species (ROS) in larvae zebrafish following exposure to pethoxamid. Increases in apoptosis and ROS, however, were not correlated with any altered gene expression pattern for apoptotic and oxidative damage response transcripts. To assess neurotoxicity potential, we measured behavior and several transcripts implicated in neural processes in the central nervous system. While locomotor activity of larval zebrafish was affected by pethoxamid exposure (hyperactivity was observed at concentrations below 1 μg L-1, and hypoactivity was noted at higher exposures to 10 and 100 μg L-1 pethoxamid), there were no effects on steady state mRNA abundance for neurotoxicity-related transcripts tested. This data contributes to knowledge regarding exposure risks for chloroacetamide-based herbicides and is the first study investigating sublethal toxicity for this newly registered herbicide.

In a previous in vivo study, adult male fathead minnows (Pimephales promelas) were exposed via water for 4 days to 1H,1H,8H,8H-perfluorooctane-1,8-diol (FC8-diol). The present study expands on the evaluation of molecular responses to this perfluoro-alcohol by analyzing 26 male fathead minnow liver RNA samples from that study (five from each test concentration: 0, 0.018, 0.051, 0.171, and 0.463 mg FC8-diol/L) using fathead minnow EcoToxChips Ver. 1.0. EcoToxChips are a quantitative polymerase chain reaction array that allows for simultaneous measurement of >375 species-specific genes of toxicological interest. Data were analyzed with the online tool EcoToxXplorer. Among the genes analyzed, 62 and 96 were significantly up- and downregulated, respectively, by one or more FC8-diol treatments. Gene expression results from the previous study were validated, showing an upregulation of vitellogenin mRNA (vtg) and downregulation of insulin-like growth factor 1 mRNA (igf1). Additional genes related to estrogen receptor activation including esr2a (estrogen receptor 2a) and esrrb (estrogen related receptor beta) were also affected, providing further confirmation of the estrogenic nature of FC8-diol. Furthermore, genes involved in biological pathways related to lipid and carbohydrate metabolism, innate immune response, endocrine reproduction, and endocrine thyroid were significantly affected. These results both add confidence in the use of the EcoToxChip tool for inferring chemical mode(s) of action and provide further insights into the possible biological effects of FC8-diol. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Herbicides are often detected in aquatic ecosystems due to residential and agricultural applications and can harm aquatic organisms once deposited into water systems. Pendimethalin is part of the dinitroaniline chemical family and is applied to crops like corn, legumes, potatoes, and soybeans. The potential toxicity of pendimethalin to aquatic species is understudied compared to other widely studied herbicides, like atrazine and glyphosate. The objectives of this review were to (1) collate information on sub-lethal responses to pendimethalin exposure in fish, (2) evaluate how exposure studies relate to environmental concentrations, and (3) identify putative bioindicators for exposure studies. Overall, studies reporting pendimethalin in water systems worldwide indicate a range of 100-300 ng/L, but levels have been reported as high as ~15 µg/g in sediment. In teleost fish, studies demonstrate developmental toxicity, immunotoxicity, and behavioral disruptions. The strongest evidence for pendimethalin-induced toxicity involves oxidative stress, although studies often test toxicity at higher concentrations than environmentally relevant levels. Using the Comparative Toxicogenomics Database, pathway analysis reveals linkages to neurotoxicity and mechanisms of neurodegeneration like \"Ubiquitin Dependent Protein Degradation\", \"Microtubule Cytoskeleton\", \"Protein Oxidation and Aggregation in Aging\", and \"Parkinson\'s Disease\". Other prominent pathways included those related to mTOR signaling and reproduction. Thus, two potential mechanisms underlying pendimethalin-induced toxicity in fish include the neural and reproductive systems. This review synthesizes current data regarding environmental fate and ecotoxicology of pendimethalin in teleost fish and points to some putative physiological and molecular responses that may be beneficial for assessing toxicity of the herbicide in future investigations.