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The fish early-life stage sublethal toxicity syndrome – A high-dose baseline toxicity response
2021
Meador, James P.
A large number of toxicity studies report abnormalities in early life-stage (ELS) fish that are described here as a sublethal toxicity syndrome (TxSnFELS) and generally include a reduced heart rate, edemas (yolk sac and cardiac), and a variety of morphological abnormalities. The TxSnFELS is very common and not diagnostic for any chemical or class of chemicals. This sublethal toxicity syndrome is mostly observed at high exposure concentrations and appears to be a baseline, non-specific toxicity response; however, it can also occur at low doses by specific action. Toxicity metrics for this syndrome generally occur at concentrations just below those causing mortality and have been reported for a large number of diverse chemicals. Predictions based on tissue concentrations or quantitative-structure activity relationship (QSAR) models support the designation of baseline toxicity for many of the tested chemicals, which is confirmed by observed values. Given the sheer number of disparate chemicals causing the TxSnFELS and correlation with QSAR derived partitioning; the only logical conclusion for these high-dose responses is baseline toxicity by nonspecific action and not a lock and key type receptor response. It is important to recognize that many chemicals can act both as baseline toxicants and specific acting toxicants likely via receptor interaction and it is not possible to predict those threshold doses from baseline toxicity. We should search out these specific low-dose responses for ecological risk assessment and not rely on high-concentration toxicity responses to guide environmental protection. The goal for toxicity assessment should not be to characterize toxic responses at baseline toxicity concentrations, but to evaluate chemicals for their most toxic potential. Additional aspects of this review evaluated the fish ELS teratogenic responses in relation to mammalian oral LD50s and explored potential key events responsible for baseline toxicity.
Mostrar más [+] Menos [-]Effects of the antineoplastic drug cyclophosphamide on the biochemical responses of the mussel Mytilus galloprovincialis under different temperatures
2021
Queirós, Vanessa | Azeiteiro, Ulisses M. | Barata, Carlos | Santos, Juan Luis | Alonso, Esteban | Soares, Amadeu M.V.M. | Freitas, Rosa
Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy treatments with high consumption rates and that has been detected in the aquatic environment. After being released into the aquatic environment, CP may cause adverse effects on aquatic organisms since antineoplastics are well-known cytotoxic, genotoxic, mutagenic and teratogenic drugs. Moreover, predicted environmental changes, such as the temperature rising, may alter the impacts caused by CP on organisms. Thus, the present study aimed to assess the effects caused by CP chronic exposure in the mussel Mytilus galloprovincialis, under actual and predicted warming scenarios. Organisms were exposed for 28 days to different concentrations of CP (10, 100, 500 and 1000 ng/L) at control (17 ± 1.0 °C) and increased (21 ± 1.0 °C) temperatures. Biochemical responses related to metabolic capacity, energy reserves, oxidative stress and neurotoxicity were assessed. The results showed that the organisms were able to maintain their metabolic capacity under all exposure conditions. However, their antioxidant defense mechanisms were activated mostly at higher CP concentrations being able to prevent cellular damage, even under the warming scenario. Overall, the present findings suggest that temperature rise may not alter the impacts of CP towards M. galloprovincialis.
Mostrar más [+] Menos [-]Disinfection by-products in drinking water: Occurrence, toxicity and abatement
2020
Srivastav, Arun Lal | Patel, Naveen | Chaudhary, Vinod Kumar
Disinfection means the killing of pathogenic organisms (e.g. bacteria and its spores, viruses, protozoa and their cysts, worms, and larvae) present in water to make it potable for other domestic works. The substances used in the disinfection of water are known as disinfectants. At municipal level, chlorine (Cl₂), chloramines (NH₂Cl, NHCl₂), chlorine dioxide (ClO₂), ozone (O₃) and ultraviolet (UV) radiations, are the most commonly used disinfectants. Chlorination, because of its removal efficiency and cost effectiveness, has been widely used as method of disinfection of water. But, disinfection process may add several kinds of disinfection by-products (DBPs) (∼600–700 in numbers) in the treated water such as Trihalomethanes (THM), Haloacetic acids (HAA) etc. which are detrimental to the human beings in terms of cytotoxicity, mutagenicity, teratogenicity and carcinogenicity. In water, THMs and HAAs were observed in the range from 0.138 to 458 μg/L and 0.16–136 μg/L, respectively. Thus, several regulations have been specified by world authorities like WHO, USEPA and Bureau of Indian Standard to protect human health. Some techniques have also been developed to remove the DBPs as well as their precursors from the water. The popular techniques of DBPs removals are adsorption, advance oxidation process, coagulation, membrane based filtration, combined approaches etc. The efficiency of adsorption technique was found up to 90% for DBP removal from the water.
Mostrar más [+] Menos [-]Determination of metals and pharmaceutical compounds released in hospital wastewater from Toluca, Mexico, and evaluation of their toxic impact
2018
Pérez-Alvarez, Itzayana | Islas-Flores, Hariz | Gómez-Oliván, Leobardo Manuel | Barceló, Damià | López De Alda, Miren | Pérez Solsona, Sandra | Sánchez-Aceves, Livier | SanJuan-Reyes, Nely | Galar-Martínez, Marcela
Due to the activities inherent to medical care units, the hospital effluent released contains diverse contaminants such as tensoactives, disinfectants, metals, pharmaceutical products and chemical reagents, which are potentially toxic to the environment since they receive no treatment or are not effectively removed by such treatment before entering the drain. They are incorporated into municipal wastewater, eventually entering water bodies where they can have harmful effects on organisms and can result in ecological damage. To determine the toxicological risk induced by this type of eflluents, eight metals and 11 pharmaceuticals were quantified, in effluent from a hospital. Developmental effects, teratogenesis and oxidative stress induction were evaluated in two bioindicator species: Xenopus laevis and Lithobates catesbeianus. FETAX (frog embryo teratogenesis assay–Xenopus) was used to obtain the median lethal concentration (LC50), effective concentration inducing 50% malformation (EC50), teratogenic index (TI), minimum concentration to inhibit growth (MCIG), and the types of malformation induced. Twenty oocytes in midblastula transition were exposed to six concentrations of effluent (0.1, 0.3, 0.5, 0.7, 0.9, 1%) and negative and positive (6-aminonicotinamide) controls. After 96 h of exposure, diverse biomarkers of oxidative damage were evaluated: hydroperoxide content, lipid peroxidation, protein carbonyl content, and the antioxidant enzymes superoxide dismutase and catalase. TI was 3.8 in X. laevis and 4.0 in L. catesbeianus, both exceed the value in the FETAX protocol (1.2), indicating that this effluent is teratogenic to both species. Growth inhibition was induced as well as diverse malformation including microcephaly, cardiac and facial edema, eye malformations, and notochord, tail, fin and gut damage. Significant differences relative to the control group were observed in both species with all biomarkers. This hospital effluent contains contaminants which represents a toxic risk, since these substances are teratogenic to the bioindicators used. The mechanism of damage induction may be associated with oxidative stress.
Mostrar más [+] Menos [-]Mycotoxins induce developmental toxicity and behavioural aberrations in zebrafish larvae
2018
Khezri, Abdolrahman | Herranz-Jusdado, Juan G. | Ropstad, Erik | Fraser, Thomas WK.
Mycotoxins are secondary metabolites produced by varieties of fungi that contaminate food and feed resources and are capable of inducing a wide range of toxicity. In the current study, we investigated developmental and behavioural toxicity in zebrafish larvae after exposure to six different mycotoxins; ochratoxin A (OTA), type A trichothecenes mycotoxin (T-2 toxin), type B trichothecenes mycotoxin (deoxynivalenol - DON), and zearalenone (ZEN) and its metabolites alpha-zearalenol (α-ZOL) and beta-zearalenol (β-ZOL). Developmental defects, hatching time, and survival were monitored until 96 h post fertilisation (hpf). The EC₅₀, LC₅₀, and IC₅₀ values were calculated. Subsequently, to assess behavioural toxicity, new sets of embryos were exposed to a series of non-lethal doses within the range of environmental and/or developmental concern. Results indicated that all the tested mycotoxins were toxic, they all induced developmental defects, and with the exception of OTA, all affected hatching time. Behavioural effects were only observed following exposure to OTA and ZEN and its metabolites, α ZOL and β ZOL. These results demonstrate that mycotoxins are teratogenic and can influence behaviour in a vertebrate model.
Mostrar más [+] Menos [-]The developmental effect of difenoconazole on zebrafish embryos: A mechanism research
2016
Mu, Xiyan | Chai, Tingting | Wang, Kai | Zhu, Lizhen | Huang, Ying | Shen, Gongming | Li, Yingren | Li, Xuefeng | Wang, Chengju
Difenoconazole is a widely used triazole fungicide and has been reported to have negative impacts on zebrafish embryos. To investigate the mechanism of its developmental toxicity, zebrafish embryos were exposed to 0.5 and 2.0 mg/L difenoconazole for 96 h. The morphological and physiological indicators of embryo development were tested. The total cholesterol (TCHO) level, triglyceride (TG) level and malondialdehyde (MDA) content were measured at 96 hpf (hours post-fertilization). In addition, the transcription of genes related to embryo development, the antioxidant system, lipid synthesis and metabolism was quantified. Our results showed that a large suite of symptoms were induced by difenoconazole, including hatching regression, heart rate decrease, growth inhibition and teratogenic effects. 0.5 mg/L difenoconazole could significantly increase the TG content of zebrafish embryos at 96 hpf, while no apparent change in the TCHO and MDA level was observed post 96 h exposure. Q-PCR (quantitative real-time polymerase chain reaction) results showed that the transcription of genes related to embryonic development was decreased after exposure. Genes related to hatching, retinoic acid metabolism and lipid homeostasis were up-regulated by difenoconazole.
Mostrar más [+] Menos [-]Thyroid hormone-disrupting activity and ecological risk assessment of phosphorus-containing flame retardants by in vitro, in vivo and in silico approaches
2016
Zhang, Quan | Ji, Chenyang | Yin, Xiaohui | Yan, Lu | Lu, Meiya | Zhao, Meirong
In recent years, phosphorus-containing flame retardants (PFRs) have been frequently detected in various environmental media and biota - and in humans - as the result of steady increase in global usage of PFRs. However, studies on the potential health and ecological risks of PFRs are still scarce. In this study, we investigated the thyroid hormone-disrupting activity and ecological risk of nine frequently detected PFRs by in vitro, in vivo and in silico approaches. Results from the dual-luciferase reporter gene assay showed that tributyl phosphate (TNBP), tricresyl phosphate (TMPP), tris(2-chloroisopropyl)phosphate (TCIPP) and tris(2-chloro-1-(chloromethyl)ethyl)phosphate (TDCIPP) exerted thyroid receptor β (TRβ) antagonistic activity, with the values of RIC20 of 5.2 × 10−7, 2.7 × 10−7, 1.2 × 10−6 and 6.8 × 10−6 M, respectively. Molecular docking platform simulations suggested that the observed effects may be attributed to direct binding of PFRs to TR. Results from the T-screen assay indicated that TNBP and TMPP showed T3 antagonistic activity and thus significantly decreased the viability of GH3 cell lines in the presence of T3. The exposure assay using Xenopus tropicalis embryos revealed the potential teratogenic effect of TNBP, TMPP, TCIPP and TDCIPP. In conclusion, our studies revealed that some PFRs were potential thyroid hormone disruptors and may cause health and ecological risks. However, the mode of action of PFRs on TR remains uncertain. The correlation between the predicted affinity and the amplitude of the effect observed in cell based assay is encouraging, but not decisive. Further in vitro binding experiments of TR and PFRs are required. At the same time, the results provided here also demonstrated that multi-model approaches are of great importance to comprehensively evaluate the potential risks of emerging contaminants.
Mostrar más [+] Menos [-]Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats
2013
Pereira, Susana P. | Pereira, Gonçalo C. | Pereira, Cláudia V. | Carvalho, Filipa S. | Cordeiro, Marília H. | Mota, Paula C. | Ramalho-Santos, João | Moreno, António J. | Oliveira, Paulo J.
The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure.
Mostrar más [+] Menos [-]Developmental alterations, teratogenic effects, and oxidative disruption induced by ibuprofen, aluminum, and their binary mixture on Danio rerio
2021
Sánchez-Aceves, Livier M | Pérez-Alvarez, Itzayana | Gómez-Oliván, Leobardo Manuel | Islas-Flores, Hariz | Barceló, Damià
Several studies highlighted the ubiquitous presence of ibuprofen and aluminum in the aquatic environment around the world and demonstrated their potential to induce embryotoxic and teratogenic defects on aquatic species individually. Although studies that evaluate developmental alterations induced by mixtures of these pollutants are scarce; and, since environmental contamination presented in the form of a mixture of toxicants with different chemical properties and toxicity mechanisms capable of generating interactions; the objective of this study was to evaluate the developmental defects, teratogenic alterations, and oxidative stress induced by individual forms and the mixture of ibuprofen (IBU) and aluminum (Al) on zebrafish embryos. Oocytes exposed to environmentally relevant concentrations of IBU (0.1–20 μg L-1) and Al (0.01–8 mg L-1) and one binary mixture. The LC50 and EC50 were obtained to calculate the teratogenic index (TI). The IBU LC50, EC50, and TI were 8.06 μg L-1, 2.85 μg L-1 and 2.82. In contrast, Al LC50 was 5.0 mg L-1with an EC50 of 3.58 mg L-1 and TI of 1.39. The main alterations observed for individual compounds were hatching alterations, head malformation, skeletal deformities, hypopigmentation, pericardial edema, and heart rate impairment. The mixture also showed significant delays to embryonic development. Moreover, oxidative stress biomarkers of cellular oxidation and antioxidant defenses at 72 and 96 hpf significantly increased. Results show that environmentally relevant concentrations of ibuprofen (IBU), aluminum (Al), and their mixture promote a series of developmental defects, teratogenic effects, and oxidative disruption on D. rerio embryos, and the interaction of both substances altered the response. In conclusion, morphological and biochemical tests are suitable tools for assessing the health risk of aquatic wildlife by exposure to individual and mixed pollutants in freshwater bodies.
Mostrar más [+] Menos [-]Heterologous expression of bacterial cytochrome P450 from Microbacterium keratanolyticum ZY and its application in dichloromethane dechlorination
2021
Hu, Jun | Zhang, Yan | Wu, Yuexin | Zheng, Jiajun | Yu, Zhiliang | Qian, Haifeng | Yu, Jianming | Cheng, Zhuowei | Chen, Jianmeng
Dichloromethane (DCM) is a volatile halogenated hydrocarbon with teratogenic, mutagenic and carcinogenic effects. Biodegradation is generally regarded as an effective and economical approach of pollutant disposal. In this study, a novel strain was isolated and its cytochrome P450 was heterologously expressed for DCM degradation. The isolate, Microbacterium keratanolyticum ZY, was characterized as a Gram-positive, rod-shaped and flagella-existed bacterium without spores (GenBank No. SUB8814364; CCTCC M 2019953). After successive whole-genome sequencing, assembly and annotation, eight identified functional genes (encoding cytochrome P450, monooxygenase, dehalogenase and hydrolase) were successfully cloned and expressed in Escherichia coli BL21 (DE3). The recombinant strain expressing cytochrome P450 presented the highest degradation efficiency (90.6%). Moreover, the specific activity of the recombinant cytochrome P450 was more than 1.2 times that of the recombinant dehalogenase (from Methylobacterium rhodesianum H13) under their optimum conditions. The kinetics of DCM degradation by recombinant cytochrome P450 was well fitted with the Haldane model and the value of maximum specific degradation rate was determined to be 0.7 s⁻¹. The DCM degradation might occur through successive hydroxylation, dehydrohalogenation, dechlorination and oxidation to generate gem-halohydrin, formyl chloride, formaldehyde and formic acid. The study helps to comprehensively understand the DCM dechlorination process under the actions of bacterial functional enzymes (cytochrome P450 and dehalogenase).
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