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Heavy metals and pesticides are significant pollutants in aquatic environments, often leading to combined pollution and exerting toxic effects on aquatic organisms. With the rapid growth of modern industry and agriculture, heavy metal cadmium (Cd) and pesticide triazophos (TRI) are frequently detected together in various water bodies, particularly in agricultural watersheds. However, the combined toxic mechanisms of these pollutants on fish remain poorly understood. This experiment involved a 21-day co-exposure of Cd and TRI to the hook snout carp Opsariichthys bidens to investigate the toxic effects on liver tissues at both enzymatic and transcriptional levels. Biochemical analysis revealed that both individual and combined exposures significantly increased the content or activity of caspase-3 (CASP-3) and malondialdehyde (MDA). Moreover, the impact on these parameters was greater in the combined exposure groups compared to the corresponding individual exposure groups. These findings suggested that both individual and combined exposures could induce mitochondrial dysfunction and lipid peroxidation damage, with combined exposure exacerbating the toxicological effects of each individual pollutant. Furthermore, at the molecular level, both individual and combined exposures upregulated the expression levels of cu-sod , cat , and erβ , while downregulating the expression of il-1. Similar to the patterns observed in the biochemical parameters, the combined exposure group exhibited a greater impact on the expression of these genes compared to the individual exposure groups. These results indicated that exposure to Cd, TRI, and their combination induced oxidative stress, endocrine disruption, and immunosuppression in fish livers, with more severe effects observed in the combined exposure group. Overall, the interaction between Cd and TRI appeared to be synergistic, shedding light on the toxic mechanisms by which fish livers responded to these pollutants. These findings contributed to the understanding of mixture risk assessment of pollutants and were valuable for the conservation of aquatic resources. [Display omitted] • Triazophos exhibited higher acute toxicity to the hook snout carps than cadmium. • Combination of cadmium and triazophos showed synergistic acute toxicity. • Cadmium and triazophos exposures induced changes in caspase-9 and MDA levels. • Expressions of ap , klf2α , il-1 , and erα were obviously altered by the co-exposure. [ABSTRACT FROM AUTHOR]

In recent years, microplastics (MPs) pollution has become a hot ecological issue of global concern and MP pollution in soil is becoming increasingly serious. Studies have shown that MPs have adverse effects on soil biology and ecological functions. Although MPs are evident in soils, identifying their source, abundance, and types is difficult because of the complexity and variability of soil components. In addition, the effects of MPs on soil physicochemical properties (PCP), including direct effects such as direct interaction with soil particles and indirect effects such as the impact on soil organisms, have not been reported in a differentiated manner. Furthermore, at present, the soil ecological effects of MPs are mostly based on biological toxicity reports of their exudate or size effects, whereas the impact of their surface-specific properties (such as environmentally persistent free radicals, surface functional groups, charge, and curvature) on soil ecological functions is not fully understood. Considering this, this paper reviews the latest research findings on the production and behavioral processes of MPs in soil, the effects on soil PCP, the impacts on different soil organisms, and the related toxic mechanisms. The above discussion will enhance further understanding of the behavioral characteristics and risks of MPs in soil ecosystems and provide some theoretical basis for further clarification of the molecular mechanisms of the effects of MPs on soil organisms. [Display omitted] • Pollution of microplastics (MPs) in soil has attracted global attention. • Indirect effects of MPs on soil physicochemical properties need attention. • Adequate attention should be paid to the enrichment of MPs by crops. • Lack of research on the health risks of MPs among soil biological chains. • Study of the toxicity mechanism of MPs should focus on their surface properties. [ABSTRACT FROM AUTHOR]

To investigate the toxic effect and mechanism of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in aquatic plants, in vivo and in vitro exposure to BDE-47 were conducted. After 14-d exposure to 5–20 μg/L BDE-47, the growth of Lemna minor plants was significantly suppressed, and the chlorophyll and soluble protein contents in fronds markedly decreased. Accordingly, the photosynthetic efficiency (Fv/Fm, PI) decreased. When the thylakoid membranes isolated from healthy fronds was exposed to 5–20 mg/L BDE-47 directly in vitro for 1 h, the photosynthetic efficiency also decreased significantly. In both the in vitro (5–20 μg/L) and in vivo (5–20 mg/L) experiments, BDE-47 led to an increased plasma membrane permeability. Hence, we concluded that BDE-47 had a direct toxicity to photosynthetic membranes and plasma membranes. However, direct effects on the activities of peroxidase (POD), malate dehydrogenase (MDH) and nitroreductase (NR) were not observed by adding 5–20 mg/L BDE-47 into crude enzyme extracts. The malondialdehyde (MDA) and superoxide anion radical (O 2 − ) contents in the BDE-47 treated fronds were higher than those in the control fronds, suggesting that L . minor can not effectively relieve reactive oxygen species (ROS). The data above indicates that BDE-47 is toxic to L . minor through acting directly on biomembranes, which induces the production of ROS and thus causes remarkable oxidative damage to cells. [ABSTRACT FROM AUTHOR]

Although modes of action (MOAs) play a key role in the understanding of the toxic mechanism of chemicals, the MOAs have not been investigated for antibiotics to green algae. This paper is to discriminate excess toxicity from baseline level and investigate the MOAs of 13 different antibiotics to algae by using the determined toxicity values. Comparison of the toxicities shows that the inhibitors of protein synthesis to bacteria, such as azithromycin, doxycycline, florfenicol and oxytetracycline, exhibit significantly toxic effects to algae. On the other hand, the cell wall synthesis inhibitors, such as cefotaxime and amoxicillin, show relatively low toxic effects to the algae. The concentrations determined by HPLC indicate that quinocetone and amoxicillin can be easily photodegraded or hydrolyzed during the toxic tests. The toxic effects of quinocetone and amoxicillin to the algae are attributed to not only their parent compounds, but also their metabolites. Investigation on the mode of action shows that, except rifampicin, all the tested antibiotics exhibit excess toxicity to Pseudokirchneriella subcapitata ( P. subcapitata) . These antibiotics can be identified as reactive modes of action to the algae. They act as electrophilic mechanism of action to P. subcapitata . These results are valuable for the understanding of the toxic mechanism to algae. [ABSTRACT FROM AUTHOR]

Despite the current efforts to identify the mixtures of chemical pollutants, they are often "binned" into their corresponding pollutant groups. Limited studies have investigated complex mixtures of chemical pollutants co-occurring across different groups. The combined toxic impacts of several substances become a critical consideration in toxicology because chemical combinations can exert a greater deleterious effect than the single components in the mixture. In the current work, we assessed the joint impacts of ochratoxin A and tricyclazole on the zebrafish (Danio rerio) embryos and explored their underlying signaling pathways. Ochratoxin A displayed higher toxicity than tricyclazole, with a 10-day LC 50 of 0.16 mg L−1, whereas that for tricyclazole was 1.94 mg L−1. The combination of ochratoxin A and tricyclazole exhibited a synergistic impact on D. rerio. The activities of detoxification enzymes GST and CYP450, as well as apoptosis-associated enzyme caspase 3, were distinctly changed in most individual and mixture exposures comparing to the untreated group. Upon both individual and mixture exposures, more dramatic variations were detected in the expressions of nine genes, such as the apoptosis genes cas3 and bax , antioxidant gene mn-sod , immunosuppression gene il-1β , and the endocrine system genes trα , dio1 , trβ , ugtlab , and crh , compared with the untreated group. These findings suggested that the simultaneous exposure to low doses of mycotoxins and pesticides in food commodities was more toxic than predicted from the individual chemicals. Considering the frequent co-occurrence of mycotoxins and pesticides in the diet, this synergy should be considered in future assessments. [Display omitted] • Ochratoxin A had a higher toxicity to embryonic zebrafish than tricyclazole. • Ochratoxin A in combination with tricyclazole showed synergistic toxicity. • CarE had an important funcion in the synergism of ochratoxin A and tricyclazole. • Expression levels of 9 genes in mixtures showed greater changes than individuals. [ABSTRACT FROM AUTHOR]

The toxic effect can be affected by pH in water through affecting the degree of ionization of ionizable compounds. Wrong classification of mode of action can be made from the apparent toxicities. In this paper, the toxicity data of 61 compounds to Daphnia magna determined at three pH values were used to investigate the effect of pH on the discrimination of excess toxicity. The results show that the apparent toxicities are significantly less than the baseline level. Analysis on the effect of pH on bioconcentration factor (BCF) shows that the log BCF values are significantly over-estimated for the strongly ionizable compounds, leading to the apparent toxicities greatly less than the baseline toxicities and the toxic ratios greatly less than zero. A theoretical equation between the apparent toxicities and pH has been developed basing on the critical body residue (CBR). The apparent toxicities are non-linearly related to pH, but linearly to fraction of unionized form. The determined apparent toxicities are well fitted with the toxicities predicted by the equation. The toxicities in the unionized form calculated from the equation are close to, or greater than the baseline level for almost all the strongly ionizable compounds, which are very different from the apparent toxicities. The studied ionizable compounds can be either classified as baseline, less inert or reactive compounds in D. magna toxicity. Some ionizable compounds do not exhibit excess toxicity at a certain pH, due not to their poor reactivity with target molecules, but because of the ionization in water. [ABSTRACT FROM AUTHOR]

Recently some novel alternative flame retardants (NFRs), which have been widely applied to meet demands for mandated flame retardation of products, have been detected in various matrices of the environment. However, knowledge on toxic effects and associated molecular mechanisms of these chemicals was limited. Here, toxic mechanisms of action of six NFRs, bis (2-ethylhexyl) phosphate (BEHP), chlorendic acid (Het acid), 2,2-bis (bromomethyl)-1,3-propanediol (BMP), tris (2-butoxyethyl) phosphate (TBEP), triethyl phosphate (TEP), tributyl phosphate (TBP) were investigated by use of a library containing ∼1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from Escherichia coli K12(E.coli) . BEHP, Het acid, BMP, TBEP, TEP, TBP inhibited growth of E. coli with 4 h 10%-inhibition concentrations of 53.0–3102.3 μM. A total of 119, 44, 26, 131, 62, 103 genes out of 336 genes selected during preliminary screening were significantly altered with fold-changes greater than 1.5 by BEHP, Het acid, BMP, TBEP, TEP and TBP, respectively. GO analyses of responsive genes suggested that RNA and primary metabolism process were involved in molecular mechanisms of toxicity. Chemical clustering based on expression of 62 multi-responsive genes showed that BEHP, TBP and TBEP were grouped together, which is consistent with similarity of their chemical structures, especially for BEHP and TBP. Clustering by molecular descriptors and molecular activity by use of the multivariate classification system ToxCast was consistent with that by profiles of multi-responsive genes. The results of this study demonstrated the utility of the E. coli, whole-cell assay for determining mechanisms of toxic action of chemicals. [ABSTRACT FROM AUTHOR]

The toxicity data of 2624 chemicals to fish, Daphnia magna , Tetrahymena pyriformis and Vibrio fischeri were used to investigate the effects of species sensitivity and bioconcentration on excess toxicity. The results showed that 47 chemical classes were identified as having the same modes of action (MOAs) to all four species, but more than half of the classes were identified as having different MOAs. Difference in chemical MOAs is one of the reasons resulting in the difference in toxic effect to these four species. Other important reasons are the difference in sensitivity and bioconcentration of species. Among the four species, V. fischeri has the most compounds identified as reactive MOA. This may be due to some compounds can be easily absorbed into the bacteria, react with the DNA or proteins, disrupt the normal function of the cell and exhibit significantly greater toxicity to the bacteria. On the other hand, the skin and lipid content of aqueous organisms can strongly inhibit the bio-uptake for some reactive compounds, resulting in a less toxic effect than expected. D. magna is the most sensitive species and T. pyriformis is the least sensitive species of the four species. For a comparison of interspecies toxicity, we need to use the same reference threshold of excess toxicity. However, some reactive compounds may be identified as baseline or less inert compounds for low sensitive species from the threshold developed from high sensitive species. The difference in the discrimination of excess toxicity to different species is not only because of the difference in MOAs for some compounds, but also due to the difference in sensitivity and bioconcentration. [ABSTRACT FROM AUTHOR]

Highlights: [•] The mode of toxic action of chemicals is species dependent. [•] Same threshold needs to be used for the discrimination of excess toxicity from narcotic effect. [•] Not all the reactive compounds exhibit excess toxicity. [•] Discrimination of less inert compounds from baseline is difficult for hydrophobic compounds. [•] Bioconcentration and experimental uncertainty can lead to mis-classification of category. [Copyright &y& Elsevier]

Ketamine is a non-competitive antagonist of NMDA glutamate receptor. It is used as an anesthetic, analgesic, sedative, and anti-depressive agent in clinical practice and also an illegal recreational drug. The increasing use has contributed to the measurable levels of ketamine in both wastewaters and hospital effluents, thereby classified as an emergent contaminant. Lately, the potential toxicity of ketamine has raised serious concerns about its iatrogenic or illicit use during pregnancy, neonatal and childhood stages. However, to assess its long-term toxicity potentially by the use of early life stages in human and rodents is limited. In this regard, the zebrafish has been considered as excellent model organism for biosafety assessments of ketamine due to it boasts an in vivo model with the advantages of an in vitro assay. In this review, we summarize the current understanding of the reported toxicity studies with ketamine in early life stage of zebrafish. The adverse effects of ketamine are known to cause overall developmental and multi-organ toxicity, including cardio-, neuro-, and skeletal toxicity. Furthermore, multiple mechanisms are found to be responsible for perpetrating toxicity of ketamine. The current findings confluence to emphasize the zebrafish embryo as an appealing model system for developmental toxicity testing in higher vertebrates. [Display omitted] • Ketamine is a dissociative anesthetic, anti-depressant and illegal recreational drug. • Zebrafish (Danio rerio) is an appealing model organism for toxicity assessment. • Ketamine induces overall developmental and multi-organ toxicities in Danio embryo. • Multiple mechanisms are found to be involved in developmental toxicity of ketamine. • The review highlights concern for the use of ketamine as a pediatric anesthetic. [ABSTRACT FROM AUTHOR]

Strobilurin fungicides are widely used pesticides in the world. They can have toxic effects not only to target organisms, but also to nontarget organisms. To assess their ecological risk, species sensitivity distributions (SSDs) are required for the development of water quality criteria (WQC). In this paper, the acute toxicity of four methoxyacrylate fungicides were experimentally determined and evaluated at 24, 48, 72 and 96 h for the species of Rana chensinensis and Limnodrilus hoffmeisteri , respectively. Acute and chronic HC 5 (5% hazard concentration) values and WQC values were calculated from SSDs based on the toxicity values determined in this paper and compiled from literature. SSDs revealed that aquatic animals were relatively sensitive species and aquatic plants are insensitive species for the four fungicides. However, different orders of species sensitivity in the acute and chronic toxicity indicated that these four fungicides had different toxic mechanisms or mode of action (MOA) to different species. According to toxicity correlation and principal component analysis (PCA), the kresoxim-methyl toxicity was very close to trifloxystrobin as compared with others due to that they are neutral compounds with very similar physicochemical properties. Quantitative structure-activity relationship (QSAR) revealed that toxicity of strobilurin fungicides were dependent both on chemical hydrophobicity and hydrogen bond basicity. These two molecular descriptors reflect the bio-uptake process and interaction of compounds with target receptors in an organism. WQC values and interspecies correlation are valuable for assessing water quality and understanding toxic mechanisms to different species. [Display omitted] • Acute toxicity of four fungicides have been determined and evaluated at 24, 48, 72 and 96 h. • Water quality criteria of acute and chronic toxicity have been developed for four strobilurin fungicides. • Toxicity of strobilurin fungicides is related with chemical hydrophobicity and hydrogen bonding potential. • The toxicity of four fungicides is not only dependent on the species, but also on the chemical structure. • Kresoxim-methyl toxicity is significantly related to trifloxystrobin toxicity because of their similar structure. [ABSTRACT FROM AUTHOR]

Fluoride generally exists in the natural environment, and has been reported to induce serious environmental hazard to animals, plants, and even humans via ecological cycle. Silkworm, Bombyx mori , which showed significant growth and reproductivity reduction when exposed to fluoride, has become a model to evaluate the toxicity of fluoride. However, the detailed mechanism underlying fluoride toxicity and corresponding transport proteins remain unclear. In this study, we performed RNA-seq of the larval midgut and fat body with fluoride exposure and normal treatment. Differential analysis showed that there were 4405 differentially expressed genes in fat body and 4430 DEGs in midgut with fluoride stress. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified several key pathways involved in the fluoride exposure and poisoning. We focused on the oxidative phosphorylation and MAPK signal pathway. QRT-PCR confirmed that oxidative phosphorylation process was remarkably inhibited by fluoride exposure and resulted in the blocking of ATP synthesis. The MAPK signal pathway was stimulated via phosphorylation signal transduction. Moreover, by protein structure analysis combined with the DEGs, we screen 36 potential membrane proteins which might take part in transporting fluoride. Taken together, the results of our study expanded the underlying mechanisms of fluoride poisoning on silkworm larval growth and development, and implied potential fluoride transport proteins in silkworm. Image 1 • 200 mg/L fluoride soaked mulberry leaves exposure inhibits the growth of silkworm larvae. • RNA-seq reveals the toxic mechanism of fluoride exposure in silkworm. • Fluoride damages oxidative phosphorylation process and disturbs MAPK signaling pathway. • The identification of potential transports for fluoride. [ABSTRACT FROM AUTHOR]

Currently, few studies have investigated the joint toxicity mechanism of azole fungicides at different exposure times and mixed at the relevant environmental concentrations. In this study, three common azole fungicides, namely, myclobutanil (MYC), propiconazole (PRO), and tebuconazole (TCZ), were used in studying the toxic mechanisms of a single substance and its ternary mixture exposed to ambient concentrations of Chlorella pyrenoidosa. Superoxide dismutase (SOD), catalase (CAT), chlorophyll a (Chla), and total protein (TP), were used as physiological indexes. Results showed that three azole fungicides and ternary mixture presented obvious time-dependent toxicities at high concentrations. MYC induced a hormetic effect on algal growth, whereas PRO and TCZ inhibit algal growth in the entire range of the tested concentrations. The toxicities of the three azole fungicides at 7 days followed the order PRO > TCZ > MYC. Three azole fungicides and their ternary mixture induced different levels of SOD and CAT activities in algae at high concentrations. The ternary mixture showed additive effects after 4 and 7 days exposure, but no effect was observed at actual environmental concentrations. The toxic mechanisms may be related to the continuous accumulation of reactive oxygen species, which not only affected protein structures and compositions but also damaged thylakoid membranes, hindered the synthesis of proteins and chlorophyll a , and eventually inhibited algal growth. These findings increase the understanding of the ecotoxicity of azole fungicides and use of azole fungicides in agricultural production. Image 1 • The toxic mechanisms can be explained by the levels of SOD and CAT activities. • The growth inhibition ratios of TP and Chla increase with the increasing chemical concentrations. • The ternary mixture showed additive effect at 4 and 7 days exposure. • The environmental concentration of ternary mixture had little effect on the four physiological indexes. [ABSTRACT FROM AUTHOR]

This study aimed to determine the chronic toxicity of the ionic liquid (IL) 1-methyl-3-octylimidazolium bromide ([C 8 mim]Br) on silver carp to further study the toxicological mechanism of ILs. For this purpose, 60-d chronic exposure at concentrations of 1.09 or 4.38 mg L -1 [C 8 mim]Br in silver carp was conducted. The results of biochemical assays revealed that [C 8 mim]Br-treatment remarkably promoted serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), acid phosphatase (ACP), and alkaline phosphatase (AKP) activities, indicating that [C 8 mim]Br-exposure caused fish organ damage. Long-term exposure of [C 8 mim]Br also altered the activities of superoxide dismutase (SOD) and catalase (CAT) and the glutathione (GSH) level but increased malondialdehyde (MDA) levels in fish brain, gill, intestine, kidney, liver, and muscle, suggesting that [C 8 mim]Br-treatment may cause oxidative stress in fish organs. Further work revealed that [C 8 mim]Br-treatment increased the activities of erythromycin-N-demethylase (ERND) and glutathione S-transferases (GST), which may participate in the metabolism of [C 8 mim]Br in fish liver. Moreover, chronic [C 8 mim]Br-exposure remarkably promoted the expression of inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB) and altered the levels of transforming growth factor-β (TGF-β), suggesting that long-term exposure of [C 8 mim]Br might promote the inflammatory response in fish liver. Additionally, [C 8 mim]Br-exposure altered succinate dehydrogenase (SDH) activity and promoted caspase-9 and caspase-3 activities in fish liver, suggesting that chronic [C 8 mim]Br-exposure also induces hepatocellular apoptosis via the mitochondrial pathway. The results presented here may be helpful to illuminate the chronic toxicity mechanism of imidazolium-based ILs and safe use of ILs in the future., (Copyright © 2018 Elsevier Ltd. All rights reserved.)