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1.
Toxicol Lett ; 325: 62-66, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32109533

RESUMO

Risk assessment for mixtures of chemicals requires to investigate the magnitude of their potential adverse effects on living organisms. This is usually done by assessing how experimental toxicological mixture data depart from the model of Loewe additivity. Several recent scientific studies propose to perform this task using an ad hoc method known as model deviation ratio (MDR) method. Moreover, the first official European regulatory document for the study of combined exposures explicitly recommends the use of the MDR method (EFSA Scientific Committee et al. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. EFSA Journal, 2019). We show here that the MDR method is not rooted in statistical principles and can lead to erroneous claims. We show however that the distribution of the MDR can be evaluated by simulations and show how this allows us to devise and carry out a bona fide statistical test. The proposed method accounts for uncertainty in the estimation of ED/EC50 and does not require a minimum sample size. The computer code developped in this study is made available as an R package called MDR.


Assuntos
Misturas Complexas/toxicidade , Relação Dose-Resposta a Droga , Modelos Estatísticos , Toxicologia/métodos , Animais , Humanos , Medição de Risco , Toxicologia/estatística & dados numéricos
2.
Chemosphere ; 239: 124802, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31521933

RESUMO

Pesticides are usually present as mixtures in water environments. Evaluating the toxic effects of individual pesticide may not be enough for protecting ecological environment due to interactions among substances. In this study, we aimed to examine the lethal doses and gene expression changes in zebrafish (Danio rerio) upon exposure to individual and mixture pesticides [malathion (MAL), chlorpyrifos (CHL) and lambda-cyhalothrin (LCY)]. Individual pesticide toxicity evaluation manifested that the toxicity of the three pesticides to D. rerio at various developmental stages (embryonic, larval, juvenile and adult stages) followed the order of LCY > CHL > MAL. On the contrary, the least toxicity to the animals was discovered from MAL. Most of the tested pesticides displayed lower toxicities to the embryonic stage compared with other life stages of zebrafish. Synergistic effects were monitored from two binary mixtures of LCY in combination with MAL or CHL and ternary mixture of MAL + CHL + LCY. The expressions of 16 genes involved in oxidative stress, immunity system, cell apoptosis and endocrine disruption at the mRNA level revealed that embryonic zebrafish were influenced by the individual or mixture pesticides. The expressions of Tnf, P53, TRα, Crh and Cyp19a exerted greater variations upon exposure to pesticide mixtures compared with their individual compounds. Collectively, the transcriptional responses of these genes might afford early warning biomarkers for identifying pollutant exposure, and the data acquired from this study provided valuable insights into the comprehensive toxicity of pesticide mixtures to zebrafish.


Assuntos
Misturas Complexas/toxicidade , Larva/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Clorpirifos/toxicidade , Interações de Medicamentos , Disruptores Endócrinos/toxicidade , Estágios do Ciclo de Vida/efeitos dos fármacos , Malation/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo
3.
Chemosphere ; 240: 124973, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726602

RESUMO

Pesticides are the chemicals of increased concern regarding their adverse environmental effects. In particular, the reports on their joint toxicity effects are scarce in the literature. Therefore, this paper describes the experiments on toxicities of four pesticides: alachlor, chlorfenvinphos, diuron, and isoproturon, toward Vibrio fischeri. In particular, the joint toxicity effects for all possible binary combinations of the pesticides were analyzed. The analysis included the application of concentration addition and independent action models at two toxicity levels: EC10 and EC50. The analysis revealed additive behavior between all pesticide pairs. The only exception was isoproturon and chlorfenvinphos whose combination resulted in synergistic toxic activity. The original form of the logistic function was given preference over the linearized form in describing the response-dose relationships of investigated pesticides.


Assuntos
Misturas Complexas/toxicidade , Praguicidas/toxicidade , Acetamidas/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Clorfenvinfos/toxicidade , Diurona/toxicidade , Interações de Medicamentos , Compostos de Fenilureia/toxicidade
4.
Ecotoxicol Environ Saf ; 187: 109823, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31639641

RESUMO

Time-dependent cross-phenomenon in which the cross between the actual concentration-response curve (CRC) for mixture crosses the CRCs for reference model varies with time has been frequently reported in previous studies, expressed as a heterogeneous pattern of joint toxic action. However, the variation tendency of time-dependent cross-phenomenon is rarely addressed. In this study, the joint toxic actions of binary antibacterial mixtures (i.e., two quorum sensing inhibitors, tetracycline hydrochloride, erythromycin, and chloramphenicol with sulfonamides) were judged using independent action (IA) model to find the variation tendency of time-dependent cross-phenomenon. The results show that the time-dependent cross-phenomena of the test binary antibacterial mixtures follow a unified variation tendency and the corresponding joint toxic actions change regularly with an increase of both concentration and time. Through investigating the relationship between the stimulatory and inhibitory modes of action for the single agents and the time-dependent cross-phenomena of binary mixtures, the regular time-dependent cross-phenomena is speculated to be derived from the hormetic effects of the components in the mixtures. This study offers an advance for the variation tendency and mechanistic explanation of time-dependent cross-phenomenon, which will provide a support for the future development in the exploration of time-dependent cross-phenomenon and environmental risk assessment of pollutant mixtures.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Antibacterianos/toxicidade , Poluentes Ambientais/toxicidade , Hormese , Aliivibrio fischeri/metabolismo , Antibacterianos/farmacocinética , Misturas Complexas/farmacocinética , Misturas Complexas/toxicidade , Poluentes Ambientais/farmacocinética , Modelos Biológicos , Percepção de Quorum/efeitos dos fármacos , Fatores de Tempo
5.
J Chem Ecol ; 45(11-12): 914-925, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31802386

RESUMO

Frogs in the genus Phyllobates are known for the presence of batrachotoxin, a highly toxic alkaloid, in their skin. Nevertheless, Phyllobates frogs from Costa Rica and Panama (P. lugubris and P. vittatus) are considered non-toxic, as they have been reported to harbor low concentrations of this alkaloid. However, the potential toxicity of Central American Phyllobates has not been assessed experimentally. Our goal was to determine the toxicity of the whole skin of P. vittatus, an endemic species from the Southeastern Pacific region of Costa Rica. We performed median lethal dose (LD50) tests in mice to determine general toxicity, and an irritant assay based on the behavioral responses of mice to subcutaneous injection, to determine differences in irritability, as a measure of toxicity, among three study localities. Using UPLC-ESI-QTOF, we obtained chemical profiles of the methanolic extract of frog skins. Due to the absence of mortality at the studied doses, we were unable to estimate LD50. However, we recorded a list of toxicity symptoms in mice that are consistent with cardiotoxic effects, and found that mice presented more symptoms at higher concentrations of skin extracts during the first hour of the LD50 assays, recovering completely at all doses by the end of the assay. On the other hand, we did not detect differences in irritability among studied localities. Additionally, we putatively identified three toxic alkaloids (Batrachotoxinin A, DHQ 251A and Lehm 275A). This study provides the first experimental data on the toxicity and associated symptoms in mice, as well as the chemical profile of the skin of P. vittatus. We suggest that the skin alkaloids of P. vitattus may confer a chemical defense towards predators.


Assuntos
Alcaloides/análise , Alcaloides/toxicidade , Anuros/fisiologia , Misturas Complexas/análise , Misturas Complexas/toxicidade , Pele/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Simulação por Computador , Costa Rica , Bases de Dados de Compostos Químicos , Feminino , Dose Letal Mediana , Camundongos Endogâmicos ICR , Venenos/análise , Venenos/toxicidade , Espectrometria de Massas em Tandem/métodos
6.
Aquat Toxicol ; 216: 105315, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561138

RESUMO

Blooms of cyanobacteria, a common event in eutrophic environments, result in the release of potentially toxic substances into the water. The cyanobacterium Radiocystis fernandoi produces microcystin (MC) and other peptides that may disturb homeostasis. This study evaluated the effect of intraperitoneal injections containing the crude extract (CE) of R. fernandoi strain R28 on the gills and kidneys of neotropical fish, Piaractus mesopotamicus, 3, 6 and 24 h post-injection. CE contained MC-RR, MC-YR and minor other oligopeptides. Plasma ions and the activities of the enzymes PP1 and PP2A, Na+/K+-ATPase (NKA), H+-ATPase (HA) and carbonic anhydrase (CA) were determined and morphological changes in both the gills and kidneys were characterized. Compared to controls, the concentration of Na+ within the plasma of P. mesopotamicus decreased after treatment with CE 3 h post treatment and increased after 24 h; the concentration of K+ decreased after 6 h. The activity of the endogenous PP1 and PP2A was unchanged in the gills and was inhibited in the kidneys 6 h after i.p. injection. In the gills, NKA activity increased after 3 h and decreased 6 h post i.p. exposure. Further, NKA activity did not differ from the controls 24-h post injection. In the kidneys, NKA, HA and CA activities were unaffected by treatment. The mitochondria-rich cell (MRC) density in the gills decreased after 3 h in the filament and 3 and 6 h in the lamellae and was restored to the control levels 24 h post-exposure. Filament epithelial hyperplasia and hypertrophy, lamellar atrophy and rupture of the lamellar epithelium were the most common effects of treatment in the gills. No histopathological changes occurred in the kidneys. This study demonstrates that a single dose of toxic CE from R. fernandoi can cause a transitory ion imbalance in P. mesopotamicus which is related to the changes in MRC levels and NKA activity. Ionic balance was recovered 24 h post i.p. injection, however, morphological changes that occurred in the gills took a longer amount of time to return to normal. To conclude, the effects of components contained within the CE of R. fernandoi may be harmful to P. mesopotamicus. In particular, the recovery of ionic regulation depends on MRC responses and histopathological changes produced by CE may affect gas exchange and other gill functions.


Assuntos
Caraciformes/fisiologia , Misturas Complexas/toxicidade , Cianobactérias/metabolismo , Exposição Ambiental , Osmorregulação , Animais , Caraciformes/sangue , Cloretos/sangue , Creatinina/sangue , Brânquias/efeitos dos fármacos , Brânquias/enzimologia , Brânquias/patologia , Íons/sangue , Rim/efeitos dos fármacos , Rim/enzimologia , Rim/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Osmorregulação/efeitos dos fármacos , Potássio/sangue , ATPases Translocadoras de Prótons/metabolismo , Sódio/sangue , ATPase Trocadora de Sódio-Potássio/metabolismo , Poluentes Químicos da Água/toxicidade
7.
Sci Total Environ ; 694: 133471, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400679

RESUMO

Stress in fish can be caused by a variety of factors and has the potential to evoke stress responses leading to a reduction of physical condition and of health. The river Werra (Germany) presents a severe case of secondary salinisation caused by potash mining activities. The model organism Danio rerio was exposed to different ion-concentrations depicting current (HT) and future (LT) threshold values of the Werra, as well as to solutions with single-exceeding ions (Mg2+ + K+ (KMg), Mg2+ (Mg) and K+ (K)). After a six-week exposure period, cortisol levels, growth and weight were measured, gills and gonads were histologically analysed and mRNA expression of follicle stimulating hormone (FSH), luteinising hormone (LH), growth hormone (GH) and prolactin (PRL) were determined. Cortisol was still elevated in fish in the HT and K group, indicating moderate stress. However, gills revealed structural changes in zebrafish in all exposure groups, size of oocytes differed in the LT and K group, male FSH mRNA levels were elevated in the HT and LT group whereas PRL mRNA levels were lower in HT and LT for both, male and female fish. These results suggest that ion-stress induces moderate effects on a variety of biological parameters that mainly serve to adapt to elevated ion concentrations. For these reasons current and even future thresholds should be reconsidered, including thresholds for total as well as single ion concentrations. Future research looking at the effects on local fish species is needed, along with regular and long-term monitoring of environmental conditions, species abundance and diversity.


Assuntos
Misturas Complexas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Testes de Toxicidade
8.
Ecotoxicol Environ Saf ; 180: 733-741, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31152987

RESUMO

A present ecological issue causing secondary salinization in different countries is the discharge of effluents by the potash mining industry. In Germany, the River Werra is used as a sink for potash mining discharges containing high concentrations of ions, predominantly Cl-, K+, Na+, and Mg2+ resulting in a strong decline of the biodiversity and abundance of local species. However, hardly anything is known about the acute and chronic physiological effects of high concentrations and imbalances of ions being prevalent in potash mining effluents in fish. Therefore, the stress response and selected immune and growth parameters were investigated in standardized laboratory experiments. A native freshwater fish species, Rutilus rutilus, was exposed to concentrations of the high currently allowed (HT) and lowered future thresholds (LT) and three different ion solutions (containing high Mg2+ (Mg), high K+ (K) and high Mg2++K+ (Mg+K) concentrations) for four different exposure times (24 h, 7 d, 21 d, 8 wk). Tank water (additionally after 9 and 12 h) and plasma cortisol, glucose and protein, hematocrit and hemoglobin were determined after each exposure time. Furthermore, plasma lysozyme and head kidney leucocyte respiratory burst activity (only after 21 d) were evaluated as well as growth parameters. A transient stress response was induced in almost all groups. Tank water cortisol was elevated after 9 h in HT, LT and Mg+K and in HT after 12 h, whereas glucose concentrations increased after 24 h in all exposure groups except K. HT led to enhanced hematocrit and hemoglobin content after 24 h. Plasma protein, immune system and growth were not affected in any group. None of the ion solutions induced acute toxicity but most triggered typical acute stress reactions. Rather the sum of high ion concentrations than single ions challenged the fish. Even though the effects observed in adult roach were only transient and indicate acclimatization under laboratory conditions, adverse effects observed in the river are evident and further research on physiological endpoints including reproductive parameters and impacts on younger life stages seem to be needed to scientifically base protective thresholds.


Assuntos
Misturas Complexas/toxicidade , Cyprinidae/fisiologia , Íons/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Aclimatação , Animais , Misturas Complexas/análise , Alemanha , Íons/análise , Mineração , Rios/química , Poluentes Químicos da Água/análise
9.
Chemosphere ; 233: 292-299, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176130

RESUMO

The exposure reality of chemicals is usually in mixtures, the effects of which are usually extrapolated from individual results. Yet, such extrapolation is challenged by the alteration between monotonic concentration-response curves (CRCs) and non-monotonic hormetic CRCs in individual and mixture effects. In the present study, we aimed to investigate the occurrence of such alterations using 1-alkylimidazolium bromide ([amim]Br) and 1-alkylpyridinium bromide ([apyr]Br) ionic liquids (ILs) as model chemicals. Effects of four [amim]Br, four [apyr]Br, and their quaternary mixtures designed by uniform design were measured on Aliivibrio fischeri in a time-dependent fashion. Results showed that the individual [amim]Br showed monotonic CRCs. Their inhibition increased over the length of the side-chain and decreased over the exposure time. The [amim]Br mixtures showed non-monotonic hormetic CRCs, where the stimulations increased over exposure time. The individual [apyr]Br had non-monotonic hormetic CRCs, and their stimulation increased over the length of the side-chain. Meanwhile, the [apyr]Br mixtures had monotonic CRCs without any stimulation. Notably, the positive contributors to the mixture effects were [emim]Br or [epyr]Br which had the shortest side-chain among the components. The findings can facilitate accurate prediction on the environmental effects of ILs with specific considerations on hormetic and mixture effects.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Líquidos Iônicos/toxicidade , Misturas Complexas/química , Misturas Complexas/toxicidade , Hormese/efeitos dos fármacos , Imidazóis/química , Imidazóis/toxicidade , Líquidos Iônicos/química , Testes de Toxicidade/métodos
10.
Toxicol Lett ; 310: 70-91, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30999039

RESUMO

The aim of the current study was to evaluate the effects of a mixture of thirteen common chemicals on rats, after a one-year exposure to doses around the acceptable daily intake (ADIs), using blood and urinary tests. The influence of low doses of the mixture on weight gain, water consumption, feed consumption and feed efficiency, biochemistry parameters, haematological parameters, blood lymphocytes subsets, serum inflammation profile and urine parameters was evaluated. Our mixture caused a moderate monotonic increase of the males' appetite and a non-monotonic increase of anabolism and a monotonic increase of appetite for the females. Regarding biochemical parameters, the exposure to the test mixture caused non-monotonic increases of AST and ALT, a decrease of PChE in males and plausibly a monotonic biliary obstruction in both sexes. Monocytes significantly increased in low dose groups of both sexes. A significant decrease of all the lymphocytes subclasses and an increased expression of TNF-α protein associated with an increased expression of IFN-γ protein observed in various groups. It became apparent that after twelve months of exposure very low doses of the tested mixture had both non-monotonic and monotonic harmful effects on different levels on rats.


Assuntos
Misturas Complexas/toxicidade , Aditivos Alimentares/toxicidade , Praguicidas/toxicidade , Testes de Toxicidade Crônica , Animais , Regulação do Apetite/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/urina , Colestase/induzido quimicamente , Citocinas/sangue , Citocinas/urina , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hormese , Mediadores da Inflamação/sangue , Mediadores da Inflamação/urina , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Ratos Sprague-Dawley , Medição de Risco , Fatores de Tempo , Ganho de Peso/efeitos dos fármacos
11.
Toxicol Lett ; 310: 14-22, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30980910

RESUMO

Mechanism of PAH mixtures, using granulosa tumour cells, was investigated. Cells were exposed to a mixture of all 16 priority PAHs (M1) or a mixture of five PAHs not classified as human carcinogens (M2). The effect of siAHR, siAHRR and siNFKB2 on the expression of CYP1A1, CYP1B1, GSTM1, ERα, AR and cell proliferation was described. M1 decreased AhR and CYP1A1, while increased AhRR and ARNT expression. M2 also decreased AhR and CYP1A1 but had no effect on AhRR expression. siAHRR reversed the inhibitory effect of M1 on AhR and CYP1A1,while inhibitory effect of M2 was still observed. siNFKB2 reversed inhibitory effect of both mixtures on AhR and CYP1A1 expression and stimulatory effect of M1 on AhRR expression. siAHR reversed stimulatory effect of both mixtures on ERα expression. Stimulatory effect of M1 on cell proliferation was not observed in siAHR, was still observed in siESR1 cells. M2 had no effect on cell proliferation, however stimulatory effect was appeared in siAHR and siESR1cells. In conclusion: M1 by activation of AhRR and NFkB p52, but M2 only by activation of NFκB attenuated AhR signalling and ligand-induced CYP1A1 expression. Interaction between AhR and ER following M1 and M2 exposure is primarily initiated through AhR.


Assuntos
Misturas Complexas/toxicidade , Tumor de Células da Granulosa , Células da Granulosa/efeitos dos fármacos , Neoplasias Ovarianas , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Metabolismo Energético/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células da Granulosa/genética , Tumor de Células da Granulosa/metabolismo , Tumor de Células da Granulosa/patologia , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Subunidade p52 de NF-kappa B/genética , Subunidade p52 de NF-kappa B/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
12.
Ecotoxicol Environ Saf ; 179: 135-142, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31035247

RESUMO

Soybean farmers are exposed to various types of pesticides that contain in their formulations a combination of chemicals with genotoxic and mutagenic potential. Therefore, the objective of this paper was to evaluate the genetic damages caused by this pesticide exposure to soybean producers in the state of Mato Grosso (Brazil), regarding biochemical, genetic polymorphic and in silico analyses. A total of 148 individuals were evaluated, 76 of which were occupationally exposed and 72 were not exposed at all. The buccal micronucleus cytome assay (BMCyt) detected in the exposed group an increase on DNA damage and cell death. No inhibition of butyrylcholinesterase (BchE) was observed within the exposed group. The detection of inorganic elements was made through the particle-induced X-ray emission technique (PIXE), which revealed higher concentrations of Bromine (Br), Rubidium (Rb) and Lead (Pb) in rural workers. A molecular model using in silico analysis suggests how metal ions can cause both DNA damage and apoptosis in the exposed cells. Analysis of the compared effect of X-ray Repair Cross-complement Protein 1 (XRCC1) and Paraoxonase 1 (PON1) genotypes in the groups demonstrated an increase of binucleated cells (exposed group) and nuclear bud (non-exposed group) in individuals with the XRCC1 Trip/- and PON1 Arg/- genes. There was no significant difference in the telomere (TL) mean value in the exposed group in contrast to the non-exposed group. Our results showed that soybean producers showed genotoxic effect and cell death, which may have been induced by exposure to complex mixtures of agrochemicals and fertilizers. In addition, XRCC1 Arg/Arg could, in some respects, provide protection to individuals.


Assuntos
Misturas Complexas/toxicidade , Dano ao DNA , Fertilizantes/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Polimorfismo Genético , Adulto , Apoptose/efeitos dos fármacos , Arildialquilfosfatase/efeitos dos fármacos , Brasil , Simulação por Computador , Células Epiteliais/efeitos dos fármacos , Fazendeiros , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/citologia , Exposição Ocupacional/análise , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética
13.
Chemosphere ; 224: 93-102, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30818199

RESUMO

In their environments, aquatic organisms are simultaneously exposed to mixtures of several endocrine disrupting compounds, including hormones. However, most of the toxicity studies so far focused on effects of single contaminants. The available information on the potential toxicity of combined hormones on microalgae is extremely limited. For these reasons the aim of this study was to evaluate the individual and mixture effect of estrone (E1), ß-estradiol (E2), estriol (E3), 17-α-ethinylestradiol (EE2), progesterone (PRO), 5-pregnen-3ß-ol-20-one (PRE), levonorgestrel (LG) and testosterone (TST) on Chlorella vulgaris and Scenedesmus armatus. Green algae cells were exposed to different concentrations (0.1-100 mg L-1) of hormones for 14 days. Biomass in the form of dry weight and chlorophyll a was examined. The decreasing order of toxicity (based on EC50, 14d) to Chlorella vulgaris and Scenedesmus armatus was: EE2>PRO > E2>PRE > TST > E3>LG > E1 and EE2>PRO > TST > E2>PRE > LG > E1>E3, respectively. Chlorella vulgaris was more sensitive to the effects of hormones than Scenedesmus armatus. Although mixed hormones were more toxic to green algae than single hormones, in the ecosystem mixtures can pose higher ecological risk than single pollutants. Therefore, data on the toxicology of both single and mixed hormones is very valuable for assessment of the possibility of adverse ecological effects caused by these pollutants. Furthermore, these results suggest that environmental exposure to hormone mixtures may cause toxicity levels different to the sum of those of the single hormones and provides a basic understanding of their toxic effect on algae.


Assuntos
Clorófitas/efeitos dos fármacos , Misturas Complexas/toxicidade , Hormônios/toxicidade , Chlorella vulgaris/efeitos dos fármacos , Chlorella vulgaris/crescimento & desenvolvimento , Clorófitas/crescimento & desenvolvimento , Disruptores Endócrinos/toxicidade , Microalgas/efeitos dos fármacos , Scenedesmus/efeitos dos fármacos , Scenedesmus/crescimento & desenvolvimento , Poluentes Químicos da Água/farmacologia
14.
Chemosphere ; 225: 565-573, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901651

RESUMO

Antifoulant Irgarol 1051 (2-methythiol-4-tert-butylamino-6-cyclopropylamino-s-triazine) can be photodegraded into M1 (2-methylthio-4-tert-butylamino-6-amino-s-triazine) and M2 (3-4-tert-butylamino-6-methylthiol-s-triazin-2-ylamino]propion-aldehyde). M3 (2-methylthio-4,6-bis-tert-butylamino-s-triazine) was also detected as a side-product in Irgarol. This study aimed to investigate the combined toxicity of a mixture of these s-triazine compounds to eight marine organisms. A degraded mixture of Irgarol in artificial seawater was obtained by photolysis over 42 d and its composition was quantified by HPLC-UV analyses. Based on short-term toxicity tests on eight selected marine species, the mixture posed significant phytotoxic effects to the cyanobacteria (Chroococcus minor and Synechococcus sp.), the diatoms (Skeletonema costatum and Thalassiosira pseudonana), the macroalgae (Ulva lactuca and Caulerpa peltata) and the dinoflagellate (Prorocentrum dentatum), though the mixture was less toxic to the copepod Tigriopus japonicus. Both Independent Action and Concentration Addition models can generate reasonably satisfactory predictions on the overall mixture toxicity to the two diatoms, implying that the four compounds likely share a similar mode of action and resemble an additive effect in the mixture.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Misturas Complexas/toxicidade , Triazinas/toxicidade , Animais , Organismos Aquáticos/metabolismo , Clorófitas/efeitos dos fármacos , Copépodes/efeitos dos fármacos , Copépodes/metabolismo , Cianobactérias/efeitos dos fármacos , Cianobactérias/metabolismo , Diatomáceas/efeitos dos fármacos , Diatomáceas/metabolismo , Dinoflagelados/efeitos dos fármacos , Testes de Toxicidade , Triazinas/análise , Triazinas/química
15.
Toxicol In Vitro ; 57: 117-125, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30776502

RESUMO

Cigarette smoking exerts diverse physiological effects including immune suppression. To better characterize the biological effects of different categories of tobacco products, a genome-wide gene expression study was performed. Transcriptomic profiling was performed in PBMCs treated with different equi-nicotine units of aqueous extracts of cigarette smoke (termed Whole Smoke-Conditioned Medium, or WS-CM), or a single dose smokeless tobacco extract (STE) prepared from reference tobacco products. WS-CM induced dose-dependent changes in the expression of several genes. No significant expression differences between low WS-CM and media control were detected. However, transcripts were significantly affected by medium WS-CM (479), high WS-CM (2, 703), and STE (2, 156). The overlap between medium WS-CM and STE, and high WS-CM and STE, was minimal (34 and 65 transcripts, respectively). Hierarchical clustering revealed that gene expression profiles for STE and medium WS-CM co-clustered, while those affected by the high dose of WS-CM clustered distinctly. Functional analysis revealed that WS-CM, but not STE, uniquely affected genes involved in immune cell development and inflammatory response. Cascades of upstream regulators (e.g., TNF, IL1ß, NFƙB) were identified for the observed gene expression changes and generally suppressed by WS-CM, but not by STE. Collectively, these findings demonstrate that combustible and non-combustible tobacco products elicit distinct biological effects, which could explain the observed chronic immune suppression in smokers.


Assuntos
Misturas Complexas/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Produtos do Tabaco , Células Cultivadas , Humanos , Leucócitos Mononucleares/metabolismo
16.
Chemosphere ; 215: 388-395, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30347356

RESUMO

Empirical data from a 6-month mesocosms experiment were used to assess the ability and performance of two machine learning (ML) models, including artificial neural network (NN) and random forest (RF), to predict temporal bioavailability changes of complex chemical mixtures in contaminated soils amended with compost or biochar. From the predicted bioavailability data, toxicity response for relevant ecological receptors was then forecasted to establish environmental risk implications and determine acceptable end-point remediation. The dataset corresponds to replicate samples collected over 180 days and analysed for total and bioavailable petroleum hydrocarbons and heavy metals/metalloids content. Further to this, a range of biological indicators including bacteria count, soil respiration, microbial community fingerprint, seeds germination, earthworm's lethality, and bioluminescent bacteria were evaluated to inform the environmental risk assessment. Parameters such as soil type, amendment (biochar and compost), initial concentration of individual compounds, and incubation time were used as inputs of the ML models. The relative importance of the input variables was also analysed to better understand the drivers of temporal changes in bioavailability and toxicity. It showed that toxicity changes can be driven by multiple factors (combined effects), which may not be accounted for in classical linear regression analysis (correlation). The use of ML models could improve our understanding of rate-limiting processes affecting the freely available fraction (bioavailable) of contaminants in soil, therefore contributing to mitigate potential risks and to inform appropriate response and recovery methods.


Assuntos
Disponibilidade Biológica , Misturas Complexas/toxicidade , Hidrocarbonetos/toxicidade , Aprendizado de Máquina , Petróleo/toxicidade , Carvão Vegetal , Misturas Complexas/farmacocinética , Poluição Ambiental/análise , Hidrocarbonetos/farmacocinética , Metais Pesados/análise , Medição de Risco , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise
17.
Sci Total Environ ; 655: 70-83, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30469070

RESUMO

Complex chemical mixtures have been widely reported in larger streams but relatively little work has been done to characterize them and assess their potential effects in headwater streams. In 2014, the United States Geological Survey (USGS) sampled 54 Piedmont streams over ten weeks and measured 475 unique organic compounds using five analytical methods. Maximum and median exposure conditions were evaluated in relation to watershed characteristics and for potential biological effects using multiple lines of evidence. Results demonstrate that mixed-contaminant exposures are ubiquitous and varied in sampled headwater streams. Approximately 56% (264) of the 475 compounds were detected at least once across all sites. Cumulative maximum concentrations ranged 1,922-162,346ngL-1 per site. Chemical occurrence significantly correlated to urban land use but was not related to presence/absence of wastewater treatment facility discharges. Designed bioactive chemicals represent about 2/3rd of chemicals detected, notably pharmaceuticals and pesticides, qualitative evidence for possible adverse biological effects. Comparative Toxicogenomics Database chemical-gene associations applied to maximum exposure conditions indicate >12,000 and 2,900 potential gene targets were predicted at least once across all sites for fish and invertebrates, respectively. Analysis of cumulative exposure-activity ratios provided additional evidence that, at a minimum, transient exposures with high probability of molecular effects to vertebrates were common. Finally, cumulative detections and concentrations correlated inversely with invertebrate metrics from in-stream surveys. The results demonstrate widespread instream exposure to extensive contaminant mixtures and compelling multiple lines of evidence for adverse effects on aquatic communities.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Misturas Complexas/toxicidade , Monitoramento Ambiental/métodos , Modelos Teóricos , Rios/química , Poluentes Químicos da Água , Misturas Complexas/análise , Ecossistema , Previsões , Estados Unidos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
18.
Food Chem Toxicol ; 125: 141-149, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30594548

RESUMO

The current study aims to assess the long-term effects of very low dose exposures to a complex chemical mixture on motor performance and behavioural changes in rats. For twelve months (equivalent to thirty years in human terms), four groups of Sprague Dawley rats (five males and five females per group) were exposed to a thirteen chemical mixture (in drinking water) in doses of 0, 0.25, 1 and 5xADI/TDI (acceptable daily intake/tolerable daily intake) (mg/kg body weight/day). After twelve month exposure, the rats' motor performances were assessed by rotarod test, and their behavioural changes were assessed by open field exploratory test and elevated plus maze test. Exposure to the chemical mixture resulted in a statistically significant increase in the locomotor activity quantified by the number of crossings over external squares and in the spatial orientation activity quantified as the number of rearings in the lower dose group (0.25xADI/TDI) compared with the control group (p < 0.05). No significant changes were observed in the two higher dose groups (1xADI/TDI, 5xADI/TDI) compared with the control group. The administration of a very low doses of a cocktail of 13 chemicals led to a dose-dependent stimulation of the nervous system, rather than its inhibition.


Assuntos
Comportamento Animal/efeitos dos fármacos , Misturas Complexas/toxicidade , Hormese , Animais , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ratos , Ratos Sprague-Dawley
20.
Chemosphere ; 219: 89-94, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30529857

RESUMO

Predicting chemical mixture toxicity is an important issue for risk assessment. Loewe's concentration addition (CA) is a major model for predicting such toxicity. The CA is an additivity-based model, and if the results of toxicity test deviate from the CA prediction, it is considered that the toxic effect of the mixture is non-additive, and that "interaction" has played some role. In the present study, using as an example a biotic ligand model (BLM), which predicts metal toxicities, we theoretically investigated the toxic effect of mixture and found that the effects are almost always non-additive if the effects are evaluated by total metal concentrations, and the non-additivity is not derived by interactions among metals but by a combination of processes of metal kinetics. Once non-additive effects are observed in chemical mixture, it is often expected that there should be some complex toxic mechanisms or some toxic interaction. Our results suggest that the expectation may not be always true. Since at least two processes are entrained in the metal toxicity (metal speciation and binding of metals to biotic ligand in BLM framework), there is a possibility that the non-additivity is generated by the combination of processes and interaction is nothing to do with it. Our results imply that toxic effects of metal mixture can be predicted more easily than we generally expected.


Assuntos
Misturas Complexas/toxicidade , Metais/toxicidade , Modelos Teóricos , Animais , Interações de Medicamentos , Ligantes , Metais/química , Medição de Risco
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