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1.
Sci Total Environ ; 703: 135551, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31767300

RESUMO

Ten grouper species grouper (n = 584) were collected throughout the Gulf of Mexico (GoM) from 2011 through 2017 to provide information on hepatobiliary polycyclic aromatic hydrocarbon (PAH) concentrations in the aftermath of the Deepwater Horizon (DWH) oil spill. Liver and bile samples were analyzed for PAHs and their metabolites using triple quadrupole mass spectrometry (GC/MS/MS) and high-performance liquid chromatography with fluorescence detection (HPLC-F), respectively. Data were compared among species and sub-regions of the GoM to understand spatiotemporal exposure dynamics in these economically and ecologically important species. Significant differences in the composition and concentrations of PAHs were detected spatially, over time and by species. The West Florida Shelf, Cuba coast and the Yucatan Shelf had a greater proportion of the pyrogenic PAHs in their livers than the other regions likely due to non-oil industry related sources (e.g., marine vessel traffic) in the regional composition profiles. Mean liver PAH concentrations were highest in the north central region of the GoM where DWH occurred. Biliary PAH concentrations and health indicator biometrics initially decrease during the first three years following the DWH oil spill but significantly increased thereafter. Increased exposures are likely explained by the resuspension of residual DWH oil as well as continued inputs from natural (e.g., seeps) sources and other anthropogenically derived sources (e.g., riverine runoff, other oil spills, and leaking oil and gas infrastructure). The increasing trend in PAH concentrations in the bile and liver of grouper species in the north central region of the GoM post-DWH suggest continued chronic exposures, however the critical stage at which permanent, irreparable damage may occur is unknown. Long-term monitoring of PAH levels and associated fish health biomarkers is necessary to evaluate impacts of chronic exposures, particularly in regions subject to intensive oil extraction activities.


Assuntos
Monitoramento Ambiental , Peixes/fisiologia , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Golfo do México , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade
2.
Sci Total Environ ; 700: 134500, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31627045

RESUMO

Flumethrin is a typical pyrethroid varroacide widely used for mite control in beekeeping worldwide. Currently, information on the toxicological characteristics of flumethrin on bees at sublethal concentrations is still lacking. To fill this gap in information, we performed a 48-h acute oral and 14-day chronic toxicity testing of flumethrin in newly emerged adult honey bees under laboratory conditions. Results showed that flumethrin had high acute toxicity to honey bees with a 48-h LD50 of 0.47 µg/bee (95% CI, 0.39 ∼ 0.57 µg/bee), which is higher than that of many other commercial pyrethroid insecticides, but lower than that of tau-fluvalinate. After 14 days of chronic exposure to flumethrin at 0.01, 0.10, and 1.0 mg/L, significant antioxidant response, detoxification, immune reaction, and apoptosis were observed in the midguts. These findings indicated that flumethrin had potential risks to bees, and it can disturb the homeostasis of bees at sublethal concentrations under longer exposure conditions. Flumethrin is highly lipophilic and easy to accumulate in beeswax; thus, careless practices might pose risks to colony development in commercial beekeeping and native populations. This laboratory study can serve as an early warning, and further studies are required to understand the real residual level of flumethrin in bees and the risks of flumethrin in field condition.


Assuntos
Abelhas/fisiologia , Inseticidas/toxicidade , Piretrinas/toxicidade , Animais , Criação de Abelhas , Dose Letal Mediana , Testes de Toxicidade Crônica
3.
Sci Total Environ ; 688: 1348-1358, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726564

RESUMO

Proliferating cyanobacterial blooms due eutrophication in reservoirs is a major global problem. The production of cyanotoxins often increases with grazing pressure and temperature while the sensitivity of zooplankton to cyanotoxins is directly related to temperature. Here we evaluate the effect of different concentrations of the crude extract of cyanobacteria from Valle de Bravo reservoir during dry (January) and rainy (September) seasons at 20 and 25 °C on the rotifer Brachionus calyciflorus based on acute and chronic toxicity tests. We filtered 20 or 150 l of lake water, depending on the intensity of the bloom, and estimated the density and diversity of the cyanobacteria. The crude extracts, after 5 cycles of freezing, thawing and sonication at 14 MHz, were filtered and the microcystin concentration quantified based on ELISA. The extracts were used to conduct the acute and chronic toxicity tests, all in quadruplicate. Acute toxicity tests were based on 24 h mortality. Chronic toxicity tests (population growth and life table experiments) were conducted at 5 and 10% of the median lethal concentration. The field samples were dominated by Microcystis sp. (January) or Woronichinia naegeliana (September). The microcystin concentration in lake water was 9.57 µg/l and 0.097 µg/l and the median lethal concentration was 5.34 µg microcystin/L and 0.35 µg microcystin/L in January and September, respectively. Survival and reproduction of B. calyciflorus were lower in the presence of the cyanobacteria crude extract, more so at 20° than at 25 °C. Our results highlight the urgency of regular monitoring based on zooplankton assays for reservoirs in tropical and temperate regions, subject to frequent and dominant cyanobacterial blooms, often as a result of climate change.


Assuntos
Cianobactérias/crescimento & desenvolvimento , Monitoramento Ambiental , Proliferação Nociva de Algas , Microcistinas/toxicidade , Rotíferos/fisiologia , Animais , Eutrofização , México , Testes de Toxicidade Crônica
4.
Ecotoxicology ; 28(9): 1105-1114, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587130

RESUMO

Pyrethroid insecticides are one of the most commonly used pesticide groups, but these compounds have brought risks to non-target species, such as amphibians. This study evaluated the toxicological effects (mortality, swimming activity and oral morphology) caused to a South American species of anuran amphibian, Physalaemus gracilis, exposed to the pyrethroids cypermethrin and deltamethrin. Total spawnings of this anuran were collected in the natural environment and transported to the laboratory where they were kept under controlled conditions. Chronic assays were defined between 0.1 and 0.01 mg L-1 of cypermethrin, and 0.009 and 0.001 mg L-1 of deltamethrin. For cypermethrin, a further chronic toxicity test was performed at 0.05 and 2.0 mg L-1, with hatchlings at stages S.20-S.25. Cypermethrin and deltamethrin were lethal enough to kill over 70% of exposed tadpoles in 1 week at concentrations that can be found in nature (0.01-0.1 mg L-1). The exposure effects also influenced swimming activity and caused changes in oral morphology, which would make it difficult for the animals to survive in their natural habitat. Both pyrethroids presented a risk for P. gracilis, so they should be re-evaluated for non-target wild species.


Assuntos
Anuros/fisiologia , Inseticidas/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Larva/efeitos dos fármacos , Larva/fisiologia , Testes de Toxicidade Crônica/veterinária
5.
Mar Pollut Bull ; 145: 254-259, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590784

RESUMO

Glassfish, Ambassis dussumieri (Cuvier, 1828), was used as a sentinel species to investigate the effects of the ingestion of environmentally relevant microplastic concentrations on juvenile fish growth and survival. Both virgin plastic and plastic collected from an urban harbour were fed to small juvenile fish daily for 95 days. Fish standard length, body depth and mass were recorded at intervals of 20 days, while survival was continuously recorded. All fish were fed tropical flakes, measured at 1.7% of the body mass per tank. Overall, fish in in plastic treatments grew less in body length and body depth compared to those control treatments. Fish mass was also lower in the virgin plastic treatment than control fish; however, the growth in mass was not significantly lower than fish in the harbour plastic treatment. The survival probability of fish in both plastic fed treatments was also lower than fish in controls.


Assuntos
Peixes/crescimento & desenvolvimento , Plásticos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Tamanho Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ecotoxicologia/métodos , Mortalidade , Testes de Toxicidade Crônica
6.
Bull Environ Contam Toxicol ; 103(6): 814-821, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606772

RESUMO

To understand the toxic mechanism of ammonia and identify effective biomarkers on the oxidative stress for the fish Carassius auratus red var., acute and chronic toxicity tests were conducted. The 96-h LC50 of total ammonia nitrogen (TAN) for C. auratus was 135.4 mg L-1, the corresponding unionized ammonia (NH3) concentration was 1.5 mg L-1. The activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione-peroxidase (GSH-Px) and glutathione (GSH) showed an increase with a subsequent falling, while the malondialdehyde (MDA) increased during the chronic test. The SOD, MDA, and GSH could be effective biomarkers to evaluate the TAN oxidative stress, the maximum acceptable toxicant concentration (MATC) was 11.3 mg L-1 for TAN. To our knowledge, this is the first study to propose biomarkers to evaluate potential environmental risk and establish a risk threshold for TAN in C. auratus.


Assuntos
Amônia/toxicidade , Aquicultura/métodos , Monitoramento Ambiental/métodos , Carpa Dourada/crescimento & desenvolvimento , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , China , Relação Dose-Resposta a Droga , Carpa Dourada/metabolismo , Dose Letal Mediana , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Urbanização
7.
Ecotoxicol Environ Saf ; 185: 109702, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585394

RESUMO

The purpose of our work was to determine the acute and chronic toxicity of three of the EU's most common herbicides - mesotrione, S-metolachlor, terbuthylazine - and their mixtures by Aliivibrio fischeri ecotoxicological assays. While comparing the sensitivity of the acute (30 min) Microtox® standard assay with the chronic (25 h) test adapted to microtiter plate, joint effects (antagonism, additive effect and synergism) to the bioluminescence inhibition (consequently the metabolic damage) in A. fischeri were also determined by Combination Index (CI) method. 30 min of exposure to mesotrione and S-metolachlor resulted in a relatively low acute toxicity (EC50 values were 118 and 265 mg/L), while terbuthylazine did not cause bioluminescence inhibition at all. Results showed that the chronic toxicity of S-metolachlor and terbuthylazine to A. fischeri (EC5010h = 59.2 and 4.9 mg/L and EC5015h = 54.0 and 9.6 mg/L, respectively) is larger by at least one order of magnitude than that after 30 min of contact time. Considering mesotrione no significant difference was experienced in toxicity. Regarding the EC50 values, all of the mixtures had synergistic joint effects in the acute assay. However, in the chronic test all the mixtures showed antagonistic responses with the exception of mesotrione and S-metolachlor (ratio 1:1) combination, which also had additive and synergistic effects after 10 and 15 h of exposure, similarly to the short-term test. This is also the first report of the joint effects of these herbicides. The chronic test is a more sensitive indicator to the active ingredients; both acute and chronic assays supply valuable data of the toxic properties of the pesticides. Moreover, the short- and long-term joint effects of their mixtures supporting a more accurate and reliable risk assessment.


Assuntos
Acetamidas/toxicidade , Aliivibrio fischeri/efeitos dos fármacos , Cicloexanonas/toxicidade , Herbicidas/toxicidade , Triazinas/toxicidade , Poluentes Químicos da Água/toxicidade , Acetamidas/química , Bioensaio , Cicloexanonas/química , Relação Dose-Resposta a Droga , Ecotoxicologia , Herbicidas/química , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Triazinas/química , Poluentes Químicos da Água/química
8.
Ecotoxicol Environ Saf ; 184: 109638, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31514080

RESUMO

Magnesium (Mg) is a common contaminant in mine water discharges. Although Mg is an essential element in biological processes, increased concentrations from anthropogenic sources can stress aquatic ecosystems. Additionally, studies evaluating the effects of Mg on north Australian freshwater species have indicated that in very soft waters there is a high risk to some species. Freshwater mussels are an ecologically and culturally important taxon in many freshwater environments, but knowledge of their sensitivity to Mg is limited. In the present study, the acute and chronic sensitivity of two freshwater mussel species, Velesunio angasi and an undescribed Velesunio species, to Mg was assessed (using MgSO4) on their early life stages, larval glochidia and post-parasitic juveniles. Acute 24-h exposures with glochidia generated a mean median lethal (LC50) toxicity estimate of 284mg/L for the five tests with V. angasi, and a mean LC50 of 300mg/L for the three tests with Velesunio sp. Mean chronic 14-d toxicity estimates resulting in 50% (EC50) and 10% (EC10) growth rate reductions for juveniles were 241 and 88mg/L respectively for the three tests with V. angasi juveniles, and 232 and 87mg/L respectively for the three tests with Velesunio sp. juveniles. The results represent the first acute and chronic Mg toxicity data for tropical freshwater mussels, and indicated that V. angasi and Velesunio sp. exhibited similar sensitivity and were moderately sensitive to Mg when compared to other tropical species. These results are a valuable contribution to the small existing dataset for Mg toxicity to tropical freshwater species, which can be used to inform water management in areas where Mg is a contaminant of concern, and ensure the protection of these taxa.


Assuntos
Bivalves/efeitos dos fármacos , Água Doce/química , Larva/efeitos dos fármacos , Magnésio/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Austrália , Ecossistema , Dose Letal Mediana , Magnésio/análise , Alimentos Marinhos , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica , Poluentes Químicos da Água/análise
9.
Toxicol Lett ; 316: 49-59, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520698

RESUMO

Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 µg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.


Assuntos
Células Epiteliais/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Pulmão/efeitos dos fármacos , MicroRNAs/genética , Material Particulado/toxicidade , RNA Mensageiro/genética , Transcriptoma/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Biologia Computacional , Bases de Dados Genéticas , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Redes Reguladoras de Genes , Humanos , Pulmão/metabolismo , Pulmão/ultraestrutura , MicroRNAs/metabolismo , Tamanho da Partícula , RNA Mensageiro/metabolismo , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Crônica
10.
Toxicol Lett ; 316: 154-170, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31521832

RESUMO

The present study investigates the genotoxic and cytotoxic effects of long term exposure to low doses of a mixture consisting of methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, buthylparaben, bisphenol A and acacia gum in rats. Four groups of ten Sprangue Dawley rats (5 males and 5 females per group) were exposed for 18 months to the mixture in doses of 0xNOAEL, 0.0025xNOAEL, 0.01xNOAEL and 0.05xNOAEL (mg/kg bw/day). After 18 months of exposure, the rats were sacrificed and their organs were harvested. Micronuclei frequency was evaluated in bone marrow erythrocytes whereas the organs were cytopathologically examined by the touch preparation technique. The exposure to the mixture caused a genotoxic effect identified only in females. Cytopathological examination showed specific alterations of tissue organization in a tissue-type dependent manner. The observed effects were dose-dependent and correlated to various tissue parameters. Specifically, testes samples revealed degenerative and cellularity disorders, liver hepatocytes exhibited decreased glycogen deposition whereas degenerative changes were present in gastric cells. Lung tissue presented increased inflammatory cells infiltration and alveolar macrophages with enhanced phagocytic activity, whereas brain tissue exhibited changes in glial and astrocyte cells' numbers. In conclusion, exposure to very low doses of the tested mixture for 18 months induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Testes de Toxicidade Crônica , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ratos Sprague-Dawley , Medição de Risco , Fatores Sexuais , Fatores de Tempo
11.
Regul Toxicol Pharmacol ; 108: 104476, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31536773

RESUMO

Tildrakizumab (also known as MK-3222), is a high-affinity, humanized, immunoglobin G1κ monoclonal antibody targeting the p19 subunit of interleukin-23 recently approved for the treatment of moderate to severe plaque psoriasis in the US, Europe, and Australia. The safety profile of tildrakizumab was characterized in nonclinical studies using a pharmacologically relevant cynomolgus monkey model. In repeat-dose toxicity studies, cynomolgus monkeys were chronically treated with subcutaneous (SC) injections of 100 mg/kg of tildrakizumab every 2 weeks up to 9 months. Tildrakizumab was well tolerated, with no toxicological findings (including assessment of reproductive organs; hormonal effects; and cardiovascular, respiratory, and central nervous system function) at systemic exposures approximately 90 times higher than the recommended human dose of 100 mg. An embryofetal developmental study conducted in pregnant monkeys revealed no treatment-related effects to the developing fetus following SC administration of tildrakizumab 100 mg/kg. In a pre- and postnatal development study, 2 neonatal deaths due to potential viral infection at 100 mg/kg were considered of uncertain relationship to the treatment based on a lack of historical data on the occurrence of viral infection in neonate cynomolgus monkeys. The results of this comprehensive nonclinical safety program support the safe use of tildrakizumab.


Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Animais , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/farmacocinética , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Subunidade p19 da Interleucina-23/sangue , Subunidade p19 da Interleucina-23/imunologia , Macaca fascicularis , Masculino , Troca Materno-Fetal , Leite/química , Gravidez , Psoríase/tratamento farmacológico , Testes de Toxicidade Crônica
12.
Ecotoxicol Environ Saf ; 183: 109486, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377518

RESUMO

The increasing use of Sertraline (SER) as antidepressant and its consequent presence in the aquatic environment is raising concern about the chronic effects of this pharmaceutical to aquatic organisms. As the current concentrations of SER in surface waters are typically in the low ng/L range, acute toxicity is unlikely to occur. However, prolonged exposure to low concentrations of SER may lead to sub-lethal effects in aquatic organisms, including alterations in important physiological functions like growth, reproduction, behaviour, and also in key biochemical processes, such as those associated with neurotransmission and redox balance. To test this hypothesis, we selected the amphipod Gammarus locusta, a keystone species used in ecotoxicological hazard assessment. In the present study, juveniles' G. locusta from a permanent laboratory culture were chronically exposed to low concentrations of SER (8-1000 ng/L) in a bioassay that lasted for 48 days, allowing for a life-cycle study including effects on reproduction. At the lowest SER concentrations with environmental relevance (8, 40 and 200 ng/L) we detected no significant changes in key ecological endpoints such as survival, growth, reproduction and movement behaviour, or in any of the biochemical markers analysed. However, at 1000 ng/L SER (a concentration one order of magnitude higher than the levels reported in aquatic environments) females showed a significant increase in movement versus control, whereas no activity changes were observed in males. Overall, these findings indicate that G. locusta females are potentially more susceptible to the chronic effects of SER. Moreover, the current environmental SER concentrations are unlikely to affect amphipod's ecological endpoints because only SER concentrations higher than the levels reported in aquatic environments produced effects on the behaviour of G. locusta females. However, the increasing consumption of SER, highlights the importance of monitoring its chronic risk to the aquatic wildlife.


Assuntos
Anfípodes/efeitos dos fármacos , Antidepressivos/toxicidade , Sertralina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Masculino , Reprodução/efeitos dos fármacos , Testes de Toxicidade Crônica
13.
Environ Pollut ; 254(Pt A): 112906, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31374489

RESUMO

Glyphosate is the active ingredient in Roundup, one of the most popular herbicides in the world, and its toxicity has caused increasing concerns. The present study aims to investigate the toxic effects of prenatal exposure to pure glyphosate or Roundup on lipid metabolism in offspring. During gestational days (GDs), ICR mice (from Institute of Cancer Research) were given distilled water, 0.5% glyphosate solution (w/v, 0.5 g/100 ml) or 0.5%-glyphosate Roundup solution orally. The livers and serum samples of the offspring were collected on gestational day 19 (GD19), postnatal day 7 (PND7) and PND21. The results showed a significant decrease in the body weight and obvious hepatic steatosis with excessive lipid droplet formation in offspring. Moreover, the concentrations of lipids such as triglycerides (TGs), total cholesterol (T-CHO), and low-density lipoprotein cholesterols (LDL-C) increased to a significant extent in both the serum and livers. Furthermore, there were significant differences in the expression levels of the genes SREBP1C, SREBP2, Fasn, Hmgcr, Hmgcs and PPARα, which are related to lipid biosynthesis or catabolism in the liver. These results demonstrate that chronic prenatal exposure to glyphosate can result in lipid metabolism disruption in the offspring of mice, as glyphosate exerts a negative influence on the expression of lipogenesis genes.


Assuntos
Glicina/análogos & derivados , Herbicidas/toxicidade , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Testes de Toxicidade Crônica , Animais , Feminino , Glicina/toxicidade , Lipídeos , Camundongos , Camundongos Endogâmicos ICR , Gravidez
14.
Aerosp Med Hum Perform ; 90(9): 807-812, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31426897

RESUMO

INTRODUCTION: The previous Spacecraft Maximal Allowable Concentrations (SMACs) for methanol were established by characterizing minor effects upon cognitive functions as a no-observable adverse effects level (NOAEL). However, an increasing awareness of the risk posed by Space-Associated Neuro-ocular Syndrome (SANS) has caused NASA Toxicology to reexamine SMACs for methanol because exposure to it can also adversely affect ocular health. An updated review of the literature indicates that no adjustments to the SMACs due to SANS complications were required, while confirming that effects upon the central nervous system remain the appropriate basis for the SMACs for methanol. Our review, however, identified several issues that provide justification for modest SMAC reductions. It has recently been recognized that inhaled methanol may reach the brain via the olfactory system and be absorbed there into the highly toxic metabolite formaldehyde. A benchmark dose (BMD) for an extra risk of 10%, derived from an analysis of the incidences of neurological lesions in monkeys chronically exposed to methanol, is an order of magnitude less than the Environmental Protection Agency's (EPA's) reference concentration for chronic inhalation of methanol. Reports calling attention to the relative insensitivity of traditional methods of assessing cognitive function erode confidence that adverse effects at the concentration reported as a NOAEL would have been recognizable. Therefore, an additional modest safety factor of three is applied to SMACs for methanol.Scully RR, Garcia H, McCoy JT, Ryder VE. Revisions to limits for methanol in the air of spacecraft. Aerosp Med Hum Perform. 2019; 90(9):807-812.


Assuntos
Cognição/efeitos dos fármacos , Metanol/toxicidade , Síndromes Neurotóxicas/prevenção & controle , Astronave/normas , Níveis Máximos Permitidos , Animais , Astronautas , Modelos Animais de Doenças , Haplorrinos , Humanos , Incidência , Concentração Máxima Permitida , Síndromes Neurotóxicas/epidemiologia , Síndromes Neurotóxicas/etiologia , Nível de Efeito Adverso não Observado , Exposição Ocupacional/normas , Testes de Toxicidade Crônica
15.
Environ Sci Pollut Res Int ; 26(26): 27444-27456, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327144

RESUMO

Air pollution represents a major health problem in megacities, bringing about 8 million deaths every year. The aim of the study was to evaluate in vivo the ocular and respiratory mucosa biological response after chronic exposure to urban air particles from Buenos Aires (UAP-BA). BALB/c mice were exposed to UAP-BA or filtered air for 1, 6, 9, and 12 months. After exposure, histology, histomorphometry, and IL-6 proinflammatory cytokine level were evaluated in the respiratory and ocular mucosa. Total cell number and differential cell count were determined in the brochoalveolar lavage fluid. In the lung, chronic exposure to UAP-BA induced reduction of the alveolar space, polymorhonuclear cell recruitment, and goblet cell hyperplasia. In the ocular surface, UAP-BA induced an initial mucin positive cells rise followed by a decline through time, while IL-6 level increased at the latest point-time assayed. Our results showed that the respiratory and the ocular mucosas respond differently to UAP-BA. Being that lung and ocular mucosa diseases may be triggered and/or exacerbated by chronic exposure to urban air PM, the inhabitants of Buenos Aires whom are chronically exposed to environmental urban air pollution may be considered a subpopulation at risk. Based on our results, we propose the ocular mucosa as a reliable and more accessible surrogate for pulmonary mucosa environmental toxicity that might also serve as an earlier biomarker for air pollution adverse impact on health.


Assuntos
Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Olho/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Poluição do Ar/análise , Animais , Argentina , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/citologia , Olho/patologia , Feminino , Interleucina-6/análise , Interleucina-6/genética , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Material Particulado/efeitos adversos , Material Particulado/análise , Material Particulado/química , Testes de Toxicidade Crônica , Urbanização
16.
Ecotoxicol Environ Saf ; 182: 109407, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279280

RESUMO

Aflatoxin B1 poses the greatest risk among the mycotoxins to target-organisms particularly human, however, no studies addressed the neurotoxicity of chronic exposure of aflatoxin. The oral dose level 1/600th of LD50 for 30, 60, and 90 days was used for three aflatoxin groups, respective to negative and vehicle control groups. Activity levels of brain antioxidants viz: superoxide dismutase, catalase, glutathione, and glutathione peroxidase significantly decreased in the three experimental durations in time-dependent trend, in contrast, lipid peroxidation showed a significant increase compared to controls. Significantly, chronic-dependent increase trend was noticed in the AF60 and AF90 group for acid phosphatase (16.1%, 35.2%), alkaline phosphatase (32.1%, 50.8%), aspartate aminotransferase (38.7%, 120.0%) and lactate dehydrogenase (30.6%, 42.1%) activities, respectively. However, a significant 23.7% decrease in the brain creatine kinase activity following 90 days of AFB1administration. Chronic administration of aflatoxin also causes alterations in activities of protein carbonyl with a maximum increase (twofold) after 90 days. Further, histopathological and immunohistochemical results confirmed time-related vasodilation, necrosis and astrocytes gliosis by high glial fibrillary acidic protein immunostaining in response to AFB1. These findings infer that long-term exposure to AFB1 results in several pathophysiological circumstances in a duration-dependent manner concerning neurodegeneration especially Alzheimer's disease.


Assuntos
Aflatoxina B1/toxicidade , Astrócitos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Poluentes Ambientais/toxicidade , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Astrócitos/imunologia , Astrócitos/patologia , Encéfalo/patologia , Relação Dose-Resposta a Droga , Proteína Glial Fibrilar Ácida/biossíntese , Imuno-Histoquímica , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Ratos , Ratos Wistar , Fatores de Tempo , Testes de Toxicidade Crônica
17.
Environ Pollut ; 253: 864-871, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349195

RESUMO

It is estimated that 10% of the worldwide population lives in the vicinity of an active volcano. However, volcanogenic air pollution studies are still outnumbered when compared with anthropogenic air pollution studies, representing an unknown risk to human populations inhabiting volcanic areas worldwide. This study was carried out in the Azorean archipelago of Portugal, in areas with active non-eruptive volcanism. The hydrothermal emissions within the volcanic complex of Furnas (São Miguel Island) are responsible for the emission of nearly 1000 tons of CO2 per day, along with H2S, the radioactive gas - radon, among others. Besides the gaseous emissions, metals (e.g., Hg, Cd, Al, Ni) and particulate matter are also released into the environment. We test the hypothesis that chronic exposure to volcanogenic air pollution alters the histomorphology of the bronchioles and terminal bronchioles, using the house mouse, Mus musculus, as bioindicator species. Mus musculus were live-captured at three different locations: two villages with active volcanism and a village without any type of volcanic activity (reference site). The histomorphology of the bronchioles (diameter, epithelium thickness, smooth muscle layer thickness, submucosa thickness and the histological evaluation of the peribronchiolar inflammation) and of the terminal bronchioles (epithelium thickness and classification) were evaluated. Mice chronically exposed to volcanogenic air pollution presented bronchioles with increased epithelial thickness, increased smooth muscle layer, increased submucosa thickness and increased peribronchiolar inflammation. Similarly, terminal bronchioles presented structural alterations consistent with bronchodysplasia. For the first time we demonstrate that chronic exposure to non-eruptive volcanically active environments causes inflammation and histomorphological alterations in mice lower airways consistent with asthma and chronic bronchitis. These results reveal that chronic exposure to non-eruptive volcanic activity represents a risk factor that can affect the health of the respiratory system of humans inhabiting hydrothermal areas.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Testes de Toxicidade Crônica , Erupções Vulcânicas , Poluentes Atmosféricos/análise , Animais , Asma , Bronquíolos/patologia , Gases , Humanos , Inflamação , Metais , Camundongos , Material Particulado , Portugal
18.
Ecotoxicol Environ Saf ; 182: 109389, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31272027

RESUMO

Simvastatin (SV), as an hypocholesterolaemic drug, has been detected in various aquatic environment. However, limited information is available on the effects of SV on freshwater invertebrates. In the present study, we investigated the toxic effects of SV on Daphnia. magna (D. magna) through measuring the physiological changes (e.g., survival, growth rate, and reproduction) in a 21-d chronic toxicity test We also determined the expression of seven detoxification and reproduction-related genes (i.e. HR96, P-gp, CYP360A8, GST, CYP314, EcR and Vtg) and several enzymes (i.e. APND, ERND, GST and CAT) in a acute test (24 h). Results showed that high concentration (e.g. 50 µg L-1) of SV for short time exposure (e.g. 24 h) significantly induced the expression of HR96 and P-gp (e.g. up to 2.5 folds)and enzymes (e.g. increasing 4.0 folds for ERND and GST activity) in D. magna.. The long-term chronic exposure (21 days) may cause the changes of life history parameters such as decreasing total egg production number per individual and intrinsic growth rates etc. SV may act as a potential endocrine disruptor to D. magna and the reproduction parameters were more sensitive endpoints than the survival and growth for evaluating SV exposure.


Assuntos
Daphnia , Disruptores Endócrinos/toxicidade , Sinvastatina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/efeitos dos fármacos , Daphnia/enzimologia , Daphnia/genética , Inativação Metabólica/efeitos dos fármacos , Inativação Metabólica/genética , Reprodução/efeitos dos fármacos , Reprodução/genética , Testes de Toxicidade Crônica
19.
Eur J Pharm Sci ; 137: 104974, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31252051

RESUMO

Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs. Prevention of adverse reactions, increase treatment adherence and success rates, providing better control of tuberculosis (TB). In this regard, obtaining new drugs with low toxicity and high tuberculostatic potential is essential. Thus, in this work, we have designed or synthesized new derivatives of isoniazid (INH), such as new Isonicotinoylhydrazone (INH-a, INH-b and INH-c). These derivatives demonstrated good biocompatibility, antimicrobial property similar to that of parent isoniazid and last but not least, a significantly improved Pharmacotoxicological profile compared to that of isoniazid.


Assuntos
Antituberculosos , Hidrazonas , Isoniazida/análogos & derivados , Animais , Antituberculosos/farmacologia , Antituberculosos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hidrazonas/farmacologia , Hidrazonas/toxicidade , Isoniazida/farmacologia , Isoniazida/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
20.
Chemosphere ; 233: 396-404, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31176903

RESUMO

We determined the effect of acute and chronic toxicity of cadmium (Cd) on Pseudodiaptomus annandalei, according to their developmental and reproductive stages. Firstly, to estimate the 50% lethal concentration (LC50), acute exposure of nauplii and copepodids to 20, 40, 80, 150, and 300 µg/L of Cd was tested, and the effects of 5 µg/L and 40 µg/L of Cd on copepod developmental rate was done. Female lifespan and number of nauplii produced were compared. Secondly, one generation of copepod was exposed to dissolved (WCd) and dietary (DCd) Cd, and sex-specific Cd uptake and population density were estimated. 96 h LC50 was 40 µg/L Cd for nauplii and 120 µg/L Cd for copepodids. Duration of copepod development was 3.5 days and 5.5 days longer than the control when exposed to 5 µg/L and 40 µg/L of Cd, respectively. Female lifespan in both treatments were 9 and 8 days shorter than in the control, respectively. Total number of nauplii produced per female lifespan was 440 (control), 450 (5 µg/L Cd), and 365 (40 µg/L Cd). Cd uptake in copepods increased from nauplii to adults when exposed to dietary Cd and decreased when exposed to dissolved Cd. Dietary uptake of Cd was significantly higher in males than in females and Cd uptake from water was higher in males than in females, but not statistically significant. The total population of copepods were significantly affected by Cd. The toxic effects of Cd in copepods appear to depend on developmental stage, sex, duration and uptake route.


Assuntos
Cádmio/toxicidade , Copépodes/efeitos dos fármacos , Traços de História de Vida , Poluentes Químicos da Água/toxicidade , Animais , Copépodes/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Masculino , Reprodução/efeitos dos fármacos , Fatores Sexuais , Testes de Toxicidade Aguda , Testes de Toxicidade Crônica
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