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1.
Chemosphere ; 242: 125293, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896202

RESUMO

The effects produced by the ethyl-carbamates: ethyl-4-bromophenyl carbamate (LQM 919) and ethyl-4-chlorophenyl carbamate (LQM 996) on the mortality and behavior of Apis mellifera were evaluated by the acute oral toxicity test and the acute contact toxicity test. The oral lethal dose, 50% of the ethyl-carbamates was >145.24 µg per bee, and the oral lethal dose, 50% of propoxur was 0.072 µg per bee. Therefore, according to the OECD criteria, the ethyl-carbamates were classified as relatively nontoxic orally; meanwhile, propoxur was classified as highly toxic orally. In the contact test, lethal concentrations 50% of the ethyl-carbamates were 4.83 and 2.23 µg/cm2 for LQM 919 and LQM 996, respectively; therefore, they were at least 10-fold less lethal (p < 0.05) than propoxur (0.22 µg/cm2). The ethyl-carbamates reduced the activity of A. mellifera acetylcholinesterase by up to 30%. The ki and kd values of both ethyl-carbamates were lower (p < 0.05) than those of propoxur and indicated that they are weak inhibitors and with low affinity to A. mellifera acetylcholinesterase, which along with the absence of behavioral alterations suggests that the mortality caused by ethyl carbamates is not related to damage to the nervous system. According to these results, the evaluated ethyl-carbamates can be considered a low ecotoxic risk for A. mellifera.


Assuntos
Acetilcolinesterase/metabolismo , Abelhas/efeitos dos fármacos , Carbamatos/toxicidade , Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Animais , Abelhas/enzimologia , Comportamento Animal/efeitos dos fármacos , Exposição Dietética/efeitos adversos , Exposição Ambiental/efeitos adversos , Dose Letal Mediana , Testes de Toxicidade Aguda
2.
Ecotoxicol Environ Saf ; 191: 110175, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954924

RESUMO

Prosulfocarb (PSC) is a thiocarbamate herbicide mainly used in winter cereals and a relevant aerosol precursor under OH radicals (OH) photooxidation conditions. We investigated the environmental risks, mechanisms, kinetics and products for the PSC withOH by employing theoretical chemical calculations. Two reaction types of H-abstraction andOH-addition reactions were taken into account. Whether in the atmosphere or aqueous particles, the most favorable pathway was the H-abstraction in the N-alkyl groups close to nitrogen atom. Subsequent reactions of primary intermediates were considered at different conditions. The total rate constants were determined as 2.62 × 10-10 cm3 molecule-1 s-1 and 4.96 × 10-11 cm3 molecule-1 s-1 at 298 K in atmosphere and aqueous particles, respectively. In natural water with theOH concentration of 10-15-10-18 mol l-1, the half-lives (t1/2) of PSC in theOH-initiated reactions were calculated as t1/2 = 2.40 × 104-2.40 × 107 s. With regard to the influence on human health and the ecosystem, oxidized products of PSC were estimated to be mutagenicity negative and had no obvious bioaccumulation potential. The aquatic toxicity of PSC and its degradation products was evaluated and the assessment results showed that the degradation of PSC was a toxicity-reduced process but they were still at toxic and harmful levels.


Assuntos
Aerossóis/química , Carbamatos/química , Poluentes Ambientais/química , Herbicidas/química , Radical Hidroxila/química , Aerossóis/toxicidade , Carbamatos/toxicidade , Poluentes Ambientais/toxicidade , Meia-Vida , Herbicidas/toxicidade , Cinética , Oxirredução , Medição de Risco
3.
Ecotoxicol Environ Saf ; 188: 109908, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706243

RESUMO

Pesticides have been extensively produced and used to help the agricultural production which leads to the contamination of the environment, soil, groundwater sources, and even foodstuffs. Fungicides carbendazim (CBZ) and chlorothalonil (Chl) are widely applied in agriculture and other aspects. CBZ or Chl have been reported to disrupt spermatogenesis and decrease semen quality. However, it is not understood the effects of pubertal exposure to low doses of CBZ and Chl together, and the underlying mechanisms. Therefore, the aim of current investigation was to explore the negative impacts of pubertal exposure to low doses of CBZ and Chl together on spermatogenesis and the role of epigenetic modifications in the process. We demonstrated that CBZ and Chl together synergize to decrease sperm motility in vitro (CBZ 1.0 + Chl 0.1, CBZ 10.0 + CHl 1.0, CBZ 100.0 + Chl 10 µM in incubation medium for 24 h) and sperm concentration and motility in vivo with ICR mice (CBZ 0.1 + Chl 0.1, CBZ 1.0 + CHl 1.0, CBZ 10.0 + Chl 10 mg/kg body weight; oral gavage for five weeks). CBZ + Chl significantly increase reactive oxygen species (ROS) and apoptosis by the increase in the protein level of caspase 8 in vitro. Moreover, CBZ + Chl synergized to disrupt mouse spermatogenesis with the disturbance in sperm production proteins and sperm proteins (VASA, A-Myb, STK31, AR, Acrosin). CBZ + Chl synergized to decrease the protein level of estrogen receptor alpha and the protein level of DNA methylation marker 5 mC in Leydig cells, and to increase the protein levels of histone methylation marker H3K9 and the methylation enzyme G9a in germ cells. Therefore, greater attention should be paid to the use of CBZ and Chl as pesticides to minimise their adverse impacts on spermatogenesis.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Epigênese Genética/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Nitrilos/toxicidade , Espermatogênese/efeitos dos fármacos , Animais , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos
4.
Anal Chim Acta ; 1094: 113-121, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761037

RESUMO

Alkaline phosphatase (ALP), an enzyme that catalyzes the hydrolysis of phosphate groups, is closely associated with many diseases, including bone disease, prostate cancer, and diabetes. Thus, new assays for ALP detection in live cells are needed to better understand its role in related biological processes. In this study, we constructed a novel near-infrared ratiometric fluorescent probe for detecting ALP activity with high sensitivity. The probe uses a new self-immolative mechanism that can achieve a rapid response (within 10 min) to ALP, detected as a spectral shift (from 580 to 650 nm). This method effectively avoids issues related to instrument variability, and the near-infrared fluorescence emission (650 nm) makes it more suitable for biological detection. Moreover, the high sensitivity (14-fold enhancement of the fluorescence ratio F650/F580) and low detection limit (0.89 U L-1) for ALP allows the probe to be adapted to complex biological environments. The assay was successfully performed using serum samples with a linear range of ALP of up to 150 U L-1. We used the developed probe to detect and image endogenous ALP in cells with satisfactory results, and we successfully used the probes to detect changes in endogenous ALP levels in zebrafish caused by drug-induced organ damage.


Assuntos
Fosfatase Alcalina/análise , Carbamatos/química , Corantes Fluorescentes/química , Organofosfatos/química , Acetaminofen/farmacologia , Animais , Carbamatos/síntese química , Carbamatos/toxicidade , Tetracloreto de Carbono/toxicidade , Bovinos , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Modelos Químicos , Organofosfatos/síntese química , Organofosfatos/toxicidade , Peixe-Zebra
5.
J Agric Food Chem ; 67(45): 12348-12356, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31638788

RESUMO

Carbosulfan is a carbamate insecticide that has been widely used in agriculture. However, studies showed that carbosulfan could be highly toxic to aquatic organisms. The metabolism of carbosulfan in adult zebrafish is still largely unexplored, and the metabolites in individual or in combination may pose a potential threat to zebrafish. In the present study, the bioaccumulation and metabolism of carbosulfan in zebrafish (Danio rerio) were assessed, and the main metabolites, including carbofuran and 3-hydroxycarbofuran, were determined. The toxicity of carbosulfan and its metabolites individually or in combination to zebrafish was also investigated. The bioaccumulation and metabolism experiment indicated that carbosulfan was not highly accumulated in zebrafish, with a bioaccumulation factor of 18 after being exposed to carbosulfan for 15 days, and the metabolism was fast, with a half-life of 1.63 d. The two main metabolites were relatively persistent, with half-lives of 3.33 and 5.68 d for carbofuran and 3-hydroxycarbofuran, respectively. The acute toxicity assay showed that carbofuran and 3-hydroxycarbofuran had 96-h LC50 values of 0.15 and 0.36 mg/L, showing them to be more toxic than carbosulfan (96-h LC50 = 0.53 mg/L). Combinations of binary or ternary mixtures of carbosulfan and its metabolites displayed coincident synergistic effects on acute toxicity, with additive index (AI) values of 1.9-14.3. In the livers and gills of zebrafish exposed to carbosulfan, carbofuran, and 3-hydroxycarbofuran, activities of catalase, superoxide dismutase, and glutathione-S-transferase were significantly changed in most cases, and the content of malondialdehyde was greatly increased, indicating that carbosulfan and its metabolites induced varying degrees of oxidative stress. The metabolites were more persistent and toxic to zebrafish and exhibit coincident synergistic effects in combination. These results can provide evidence for the potential risk of pesticides and highlight the importance of a systematic assessment for the combination of the precursor and its metabolites.


Assuntos
Carbamatos/metabolismo , Carbamatos/toxicidade , Inseticidas/metabolismo , Inseticidas/toxicidade , Peixe-Zebra/metabolismo , Animais , Carbofurano/análogos & derivados , Carbofurano/metabolismo , Carbofurano/toxicidade , Catalase , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Dose Letal Mediana , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
6.
Environ Sci Pollut Res Int ; 26(30): 31133-31141, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31463752

RESUMO

To improve crop yielding, a large amount of fungicides is continuously applied during the agricultural management, while the effects of fungicides residues on microbial processing of N in soil need further study. In the present study, two broad spectrum fungicides, chlorothalonil and carbendazim, were applied at the rates of 5, 10, and 50 mg of active ingredient (A.I.) per kg of dry soil combined with urea with 200 mg of N per kg of dry soil under laboratory conditions. The results showed that chlorothalonil obviously retarded the hydrolysis of urea, whereas carbendazim accelerated it in 4 days after the treatments (P < 0.05). Chlorothalonil reduced denitrification, nitrification, and N2O production (P < 0.05), but not for carbendazim. Further analysis on N-associated microbial communities showed chlorothalonil reduced nitrosomonas populations at the rates of 10 and 50 mg of A.I. per kg and autotrophic nitrifying bacterial populations at three application rates (P < 0.05), but Carbendazim decreased nitrosomonas populations only at the rate of 50 mg of A.I. per kg and also autotrophic nitrifying bacterial populations at three rates and heterotrophic nitrifying bacterial populations at the rates of 10 and 50 mg of A.I. per kg. The reasons for this difference were ascribed to arrest urea hydrolysis and impediment of denitrification and nitrification processes by chlorothalonil. In conclusion, to improve crop yielding, chlorothalonil might be more beneficial to conserve soil N by improving soil N fertility, compared with carbendazim.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Nitrilos/toxicidade , Nitrogênio/metabolismo , Microbiologia do Solo , Ureia/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Desnitrificação/efeitos dos fármacos , Fertilizantes , Fungicidas Industriais/toxicidade , Hidrólise , Nitrificação/efeitos dos fármacos , Nitrogênio/química , Solo/química , Ureia/química
7.
J Steroid Biochem Mol Biol ; 194: 105457, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31454535

RESUMO

Breast cancer is the most prevalent cancer in women affecting about 12% of world's female population. It is a multifactorial disease, mostly invasive in nature. Diosgenin and related compounds are potent antiproliferative agents. Carbamate derivatives have been synthesized at C26 of furostene ring after opening spiroketal bond (F-ring) of diosgenin. Compound 10 possessed significant antiproliferative activity against human breast cancer cells by arresting the population at G1 phase of cell division cycle and induced apoptosis. Induction of apoptosis was observed through the caspase signalling cascade by activating caspase-3. Moreover, carbamate 10 exhibited moderate antiinflammatory activity by decreasing the expression of cytokines, TNF-α and IL-6 in LPS-induced inflammation in primary macrophage cells. Furthermore, compound 10 significantly reduced Ehrlich ascites carcinoma significantly in mice. It was well tolerated and safe in acute oral toxicity in Swiss albino mice. The concomitant anticancer and antiinflammatory properties of carbamate 10 are important and thus, can further be optimized for a better anti-breast cancer candidate.


Assuntos
Anti-Inflamatórios , Antineoplásicos , Carbamatos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Carbamatos/toxicidade , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Caspase 3/metabolismo , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Simulação de Acoplamento Molecular , Carga Tumoral/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
8.
Environ Pollut ; 252(Pt A): 51-61, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146238

RESUMO

Melatonin (Mel) serves as an important signalling molecule in various aspects of stress tolerance in plants. However, the function of Mel in pesticide metabolism remains unknown. Here, selecting the widely used fungicide carbendazim (MBC) as the model, we found that exogenous Mel had the ability to alleviate pesticide phytotoxicity and residues in tomato as well as in some other vegetables. Additionally, overexpression of the Mel biosynthetic gene caffeic acid O-methyltransferase 1 (COMT1) significantly enhanced the capacity of the tomato to reduce MBC phytotoxicity and residue. This outcome was mainly because of the Mel-induced antioxidant capability, as well as the key detoxification process. Indeed, levels of reactive oxygen species (ROS) and lipid peroxides significantly decreased after applying exogenous Mel or overexpressing COMT1, which resulted from direct ROS scavenging, and increased Mel levels significantly enhanced antioxidant enzymatic activity. More importantly, Mel activated the ascorbate-glutathione cycle to participate in glutathione S-transferase-mediated pesticide detoxification. A grafting experiment showed that rootstocks from COMT1 transgenic plants increased the Mel accumulation of wild-type scions, resulting in MBC metabolism in the scions. To our knowledge, this is the first report providing evidence of Mel-induced pesticide metabolism, which provides a novel approach for minimizing pesticide residues in crops by exploiting plant self-detoxification mechanisms.


Assuntos
Benzimidazóis/metabolismo , Carbamatos/metabolismo , Fungicidas Industriais/metabolismo , Inativação Metabólica/fisiologia , Lycopersicon esculentum/metabolismo , Melatonina/metabolismo , Metiltransferases/metabolismo , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Fungicidas Industriais/toxicidade , Glutationa Transferase/metabolismo , Peróxidos Lipídicos/metabolismo , Melatonina/biossíntese , Metiltransferases/biossíntese , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
J Agric Food Chem ; 67(24): 6683-6690, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31140797

RESUMO

Fungicides are frequently detected in natural water and have gained increasing attention as a result of their potential toxicity to non-target aquatic organisms. Carbendazim (CAR), a commonly used fungicide, was selected to explore its toxicity and biodegradation in a typical freshwater diatom Navicula sp. Results showed that the growth of Navicula sp. was inhibited by CAR, with a 24 h EC50 value of 2.18 mg L-1. Although the algal growth rate was recovered after 72 h of exposure, the chlorophyll a content remained significantly decreased when the concentration of CAR was above 0.5 mg L-1. Moreover, Navicula sp. had a negative effect on the removal of CAR, and the acute toxicity by CAR was likely due to its rapid accumulation in algal cells. Mass spectrometric data revealed the transformation products of CAR from hydroxylation, methylation, decarboxylation, demethylation, and deamination in algal cultures. These results provide a better understanding of the environmental risks of CAR in water and point to the need for additional studies on the potential adverse biological effects of its intermediates.


Assuntos
Benzimidazóis/metabolismo , Carbamatos/metabolismo , Diatomáceas/metabolismo , Fungicidas Industriais/metabolismo , Poluentes Químicos da Água/metabolismo , Benzimidazóis/química , Benzimidazóis/toxicidade , Carbamatos/química , Carbamatos/toxicidade , Diatomáceas/química , Diatomáceas/efeitos dos fármacos , Diatomáceas/crescimento & desenvolvimento , Água Doce/análise , Fungicidas Industriais/química , Fungicidas Industriais/toxicidade , Espectrometria de Massas , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade
10.
Environ Sci Pollut Res Int ; 26(16): 16289-16302, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30980366

RESUMO

Aquatic organisms might be exposed episodically or continuously to chemicals for long-term periods throughout their life span. Pesticides are one example of widely used chemicals and thus represent a potential hazard to aquatic organisms. In addition, these chemicals may be present simultaneously in the environment or as pulses, being difficult to predict accurately how their joint effects will take place. Therefore, the aim of the present study was to investigate how Daphnia magna (clone k6) exposed throughout generations to a model pesticide (the fungicide carbendazim) would react upon an exposure to another chemical compound (triclosan) and to a mixture of both chemicals (carbendazim and triclosan). Responses of daphnids continuously exposed to carbendazim and kept in clean medium will be compared using immobilization tests and the comet assay (DNA integrity). The results showed that triclosan presented similar toxicity to daphnids exposed for 12 generations (F12) to carbendazim (similar 48-h-LC50 values for immobilization data), when compared with daphnids kept in clean medium. However, at subcellular level, daphnids previously exposed to carbendazim for 12 generations (F12) showed different responses than those from clean medium, presenting a higher toxicity; a general higher percentage of DNA damage was observed, after exposure to a range of concentrations of triclosan and to the binary combination of triclosan + carbendazim. The patterns of toxicity observed for the binary mixture triclosan + carbendazim were generally similar for daphnids in clean medium and daphnids exposed to carbendazim, with a dose level deviation with antagonism observed at low doses of the chemical mixture for the immobilization data and a dose ratio deviation with synergism mainly caused by triclosan for DNA damage. With this study, we contributed to the knowledge on long-term induced effects of carbendazim exposure, while looking at the organismal sensitivity to another chemical (triclosan) and to a mixture of carbendazim and triclosan using lethality as an endpoint at the individual level and DNA damage as a subcellular endpoint.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Daphnia/efeitos dos fármacos , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Daphnia/fisiologia , Ecotoxicologia/métodos , Fungicidas Industriais/toxicidade , Praguicidas/toxicidade , Testes de Toxicidade Crônica
11.
Environ Toxicol Pharmacol ; 69: 51-56, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30953934

RESUMO

In 2008, 30 active substances from plant protection products were banned from marketing in France. Nevertheless, the French Poison Control Centers continue to see cases of poisoning caused by these active substances that are no longer approved. The aim of this study was to describe the characteristics of the reported cases in mainland France and in overseas French territories, over the period 2012-2016. A total of 408 cases of human exposure were reported during the study period. The most commonly reported substances were dichlorvos (24.8%, n = 108), paraquat (23.8%, n = 97), aldicarb (14.7%, n = 60), diuron (9.6%, n = 39), dinocap (5.1%, n = 21), methomyl (4.2%, n = 17), carbofuran (3.9%, n = 16), anthraquinone (2.9%, n = 12) and carbendazim (2.7%, n = 11). The number of cases of intoxication dropped sharply between 2012 (n = 119) and 2016 (n = 47), except in the overseas French territories. Among the 72 serious cases (severe or life-threatening or with a fatal outcome), the most common substances involved were paraquat (n = 34), aldicarb (n = 24) and carbofuran (n = 7). This study suggests persistent use of carbamate insecticides, the existence of illegal imports of dichlorvos or paraquat-based products, and the use of certain banned fungicides in the professional agricultural sector. Information and collection campaigns are therefore essential after the withdrawal of marketing authorization for the plant protection products.


Assuntos
Exposição Ambiental/efeitos adversos , Praguicidas/toxicidade , Centros de Controle de Intoxicações/tendências , Adolescente , Adulto , Idoso , Carbamatos/toxicidade , Criança , Pré-Escolar , Diclorvós/toxicidade , Exposição Ambiental/legislação & jurisprudência , Exposição Ambiental/prevenção & controle , Feminino , França , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Paraquat/toxicidade , Adulto Jovem
12.
Ecotoxicol Environ Saf ; 176: 242-249, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30939404

RESUMO

Pesticides, fungicides are reportedly involved in a decline in spermatozoa quality, especially motility, and a consequent increase in the rate of infertility. Fungicide carbendazim (CBZ) is widely used in agriculture and other aspects. Although CBZ is known to disrupt spermatogenesis, causing a decrease in spermatozoa concentration and motility, the mechanisms are not fully understood. We aimed to further explore the underlying mechanisms of CBZ disruption of spermatogenesis. Pubertal mice were exposed to low doses (0.1, 1 and 10 mg/kg body weight) of CBZ for 5 weeks, then many factors related to spermatogenesis have been explored. It was found that 0.1-10 mg/kg body weight of CBZ exposure decreased mouse sperm motility and concentration, diminished the important protein factors (VASA, PGK2, B-Amy and CREM) for spermatogenesis, reduced sperm protein acrosin level, disrupted very vital epigenetic factors H3K27, 5 mC and 5 hmC. Furthermore, CBZ exposure damaged estrogen receptor alpha (ERα) pathway by decreased the protein levels of ERα and its targets PI3K and AKT. In summary low doses of CBZ exposure disrupted mouse spermatogenesis through estrogen receptor signaling; and that histone methylation and DNA methylation might play vital roles in CBZ disturbance of spermatogenesis through intertwining with estrogen signaling pathways. CBZ from the contamination in environment or food chain poses a serious threat to the normal development of spermatozoa. Therefore we strongly recommend to minimise the use of CBZ since it causes the severe issues on spermatogenesis.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Metilação de DNA/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Histonas/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Estrogênios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/metabolismo
13.
Environ Int ; 127: 199-205, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30928843

RESUMO

Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14-1.81) compared with never users. Categories using tertiles of duration (<4 yrs., 4-12 yrs., and >12 yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR<4vsUnex = 1.33 (0.88, 2.03), OR4-12vsUnex = 1.42 (1.02, 1.96), OR>12vsUnex = 1.55 (1.05, 2.28, p-trend < 0.01)). In addition, malathion use was statistically significantly associated with FL (OR = 1.58; 95% CI: 1.11-2.27) and DLBCL (OR = 1.61; 95% CI: 1.16-2.22) while there were no apparent associations with SLL or other subtypes, the p-value for heterogeneity across subtypes, however, was not significant. These results support previous studies suggesting an association between insecticide use and NHL overall, and provide new information on associations with NHL subtypes.


Assuntos
Carbamatos/toxicidade , Inseticidas/toxicidade , Linfoma não Hodgkin/induzido quimicamente , Organofosfatos/toxicidade , Idoso , Canadá , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Praguicidas , Fatores de Risco , Estados Unidos
14.
Ecotoxicol Environ Saf ; 176: 219-225, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30933896

RESUMO

The toxicity of the ixodicidal carbamates ethyl-4-bromophenyl carbamate (LQM 919), ethyl-4-chlorophenyl carbamate (LQM 996) and propoxur on Eisenia foetida adults was evaluated to estimate their ecotoxic potential. The earthworm mortality and weight loss produced by the three evaluated carbamates showed a concentration-dependent effect (p < 0.0001) in the contact filter paper test (CFPT). In the artificial soil test (AST), mortality increased in relation to the exposure time (p < 0.0001) and the concentration (p < 0.01) of the carbamates. Only the earthworms exposed in the CFPT showed morphological alterations. According to the LC50 obtained in the CFPT, the three carbamates were classified as very toxic and, according to the LC50 obtained in the AST, the three carbamates were classified as highly toxic for E. foetida. The values of ki and kd indicated that LQM 919 and LQM 996 are weak inhibitors with lower affinity for the acetylcholinesterase of E. foetida than that of propoxur. The concentrations in the CFPT and AST at which 100% mortality was observed in E. foetida were 64- and 4-fold higher, respectively, than the egg hatching inhibitory concentration 99% reported for ticks.


Assuntos
Acetilcolinesterase/metabolismo , Carbamatos/toxicidade , Oligoquetos/efeitos dos fármacos , Propoxur/toxicidade , Poluentes do Solo/toxicidade , Animais , Dose Letal Mediana , Oligoquetos/enzimologia , Solo/química
15.
Toxicol In Vitro ; 58: 78-85, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30851412

RESUMO

The fungicide Carbendazim is widely used in agriculture and preservation of films and fibers. In mammals, it can promote germ cell mutagenicity, carcinogenicity, and reproductive toxicity. However, few data about the effects of this toxicant upon the respiratory system are available. In this work, we evaluated Carbendazim toxicity upon A549 alveolar cells both in monolayer and upon air-liquid interface cell system. Monolayer cell exposed to non-cytotoxic concentrations of this fungicide showed cell arrest at G2/M phase, and did not show additional alterations. On the other hand, alveolar 3D reconstructed epithelial model (air-liquid interface cell system) was characterized and exposed to IC25 of Carbendazim using the Vitrocell® Cloud 12 chamber. Expression of Active Caspase-3, α-tubulin and ROS was significantly increased after such exposure. Mitochondrial activity was also reduced after exposed to Carbendazim. The obtained results indicate that besides the environmental and reproductive toxicity concerns regarding Carbendazim exposure, pulmonary toxicity must be considered for this fungicide. In addition, we observed that the way of exposure impacts considerably on the cell response for in vitro assessment of chemicals inhalation toxicity profile.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Benzimidazóis/toxicidade , Carbamatos/toxicidade , Técnicas de Cultura de Células/métodos , Fungicidas Industriais/toxicidade , Células A549 , Células Epiteliais Alveolares/metabolismo , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo
16.
Chemosphere ; 223: 48-57, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30763915

RESUMO

Insect cytochrome P450 monooxygenase (CYP) plays a key role in the detoxification of insecticides. In this study, four cDNA sequences of CYP6 genes were identified and characterized. Transcription levels of LmCYP6HC1 and LmCYP6HCL1 were high in first- and fourth-instar nymph stages, respectively. LmCYP6HN1 was primarily expressed in the egg to third-instar nymph stages, while LmCYP6HQ1 was predominantly expressed in the stages from fourth-instar nymph to the adult. The four CYP6 genes were predominantly distributed in the antenna, brain, fat body, integument, and hemolymph. Piperonyl butoxide exposure inhibited total CYP activity and synergized the toxicity of carbamates and pyrethroids. Knockdown of LmCYP6HL1, LmCYP6HN1, and LmCYP6HQ1 increased nymph mortality following exposure to carbaryl, and silencing of LmCYP6HC1, LmCYP6HL1, LmCYP6HN1, and LmCYP6HQ1 comprehensively raised nymph mortality following exposure to fluvalinate. Knockdown of LmCYP6HL1 or LmCYP6HN1 significantly increased nymph mortality following exposure to cypermethrin or fenvalerate, respectively. These results suggest that the CYP6 family plays a key role in determining the susceptibility of Locusta migratoria to both carbamates and pyrethroids.


Assuntos
Carbamatos/toxicidade , Família 6 do Citocromo P450/genética , Locusta migratoria/enzimologia , Piretrinas/toxicidade , Animais , Inativação Metabólica , Inseticidas/metabolismo , Locusta migratoria/efeitos dos fármacos , Ninfa/efeitos dos fármacos , Butóxido de Piperonila/toxicidade
17.
Ecotoxicol Environ Saf ; 173: 494-503, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30802738

RESUMO

Estuarine environments gather pollution from large regions including urban and industrial zones. The monitoring of environmental quality in these areas constitutes a real requirement for global sustainable development. Therefore, the aim of this study was to characterize the physicochemical and kinetic parameters of brain acetylcholinesterase (AChE) in the species Centropomus undecimalis, Diapterus auratus and Diapterus rhombeus and to assess the effects (in vitro) of pesticides and metal ions on their respective activities in order to investigate them as potential biomarkers. Physicochemical properties such as thermostability, optimal pH and temperature, as well as kinetic parameters were investigated. AChE was pointed as the predominant cholinesterase (ChE) in the brains of the species under study. The highest optimum pH value was observed for C. undecimalis (8.0), and the lowest for D. rhombeus and D. auratus, with 7.2 and 7.0, respectively. The optimal temperature was 35 °C for the three species. The AChEs of the three species presented moderate thermostability, since they retained 61%, 72% and 67% of the activity up to 45 °C (C. undecimalis, D. auratus and D. rhombeus, respectively). The carbamate carbofuran showed to be the strongest inhibitor even at very low concentrations (IC50: 0.182, 0.174 and 0.203 µmol/L - C. undecimalis, D. auratus and D. rhombeus, respectively), followed by dichlorvos and carbaryl. According to the findings, the AChE of these species may be proposed as in vitro biomarker of exposure to carbofuran and dichlorvos (all three species) and carbaryl (D. auratus and D. Rhombeus), as well as for exceeding limit concentrations of Hg2+ (D. rhombeus) and As3+ (D. auratus) in biomonitoring programs located or not at estuarine environments.


Assuntos
Acetilcolinesterase/metabolismo , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/toxicidade , Proteínas de Peixes/metabolismo , Perciformes/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Arsênico/toxicidade , Encéfalo/enzimologia , Carbamatos/toxicidade , Diclorvós/toxicidade , Cinética , Metais Pesados/toxicidade , Praguicidas/toxicidade
18.
Aquat Toxicol ; 209: 34-41, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30685545

RESUMO

The potential risk and toxic mechanisms of fenobucarb (2-sec-butylphenyl methylcarbamate, BPMC) to animals and humans have not been fully elucidated. In this study, zebrafish embryos were exposed to various concentrations of BPMC from 48 hpf (hour post fertilization, hpf) to 72 hpf. We found that BPMC induced severe heart failure with bradycardia, reduced heart contractions, cardiac output and blood flow dynamics;and myocardial apoptosis. BPMC also induced cerebral hemorrhages and blood erythrocyte reduction in a dose-dependent manner. Also observed were increased ROS production and capase 9 and 3/7 activation. The mRNA levels of the ATPase-related gene (atp2a1l), calcium channel-related gene (cacna1ab), sodium channel-related gene (scn5Lab), potassium channel-related gene (kcnq1), the regulatory gene (tnnc1a) for cardiac troponin C, and several apoptosis-related genes were significantly downregulated in zebrafish following BPMC exposure. These results suggest that exposure to BPMC is a possible risk factor to cardiovascular and cerebrovascular systems in animals.


Assuntos
Carbamatos/toxicidade , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/complicações , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/complicações , Peixe-Zebra/metabolismo , Animais , Apoptose/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Caspases/metabolismo , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Dilatação Patológica , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hiperemia/complicações , Espécies Reativas de Oxigênio/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
19.
Environ Toxicol Chem ; 38(2): 412-422, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30508263

RESUMO

Anthropogenic activities such as the use of pesticides may affect aquatic biota populations, due to potential agricultural runoffs or disposals. Carbendazim is one example of a widely used fungicide with a high potential to end up in aquatic ecosystems through runoff. Deleterious effects observed at the individual level are possibly explained by changes in homeostasis at the cellular level, and both factors can then be used to predict effects at the population level. In the present study, an isoclonal population of Daphnia magna (clone K6) was exposed to a concentration that mimics relevant levels of carbendazim in the environment over 12 generations. The effects of carbendazim were assessed in some generations using the following endpoints: biochemical biomarkers (cholinesterase, catalase, and glutathione-S-transferase), lipid peroxidation and energy-related parameters (carbohydrates, lipids, and proteins along with available energy and energy consumption), parental longevity, and population growth (r). Long-term exposure to carbendazim had no effect on the intrinsic rate of natural increase (r) of adult D. magna, but longevity was decreased at the F12 generation compared to that of control. Differences between the exposed and nonexposed populations were found for cholinesterase, glutathione-S-transferase, and lipid peroxidation. However, for catalase and energy-related parameters, no differences were observed between these 2 populations. Natural variability was seen throughout the test period, under control conditions, within the 12 generations. Overall, carbendazim induced some effects at the subcellular level that translated into changes in longevity but these later vanished in terms of population effects. Environ Toxicol Chem 2019;38:412-422. © 2018 SETAC.


Assuntos
Benzimidazóis/toxicidade , Carbamatos/toxicidade , Daphnia/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia/enzimologia , Daphnia/crescimento & desenvolvimento , Ecossistema , Peroxidação de Lipídeos/efeitos dos fármacos , Longevidade , Reprodução/efeitos dos fármacos
20.
Acta Biochim Biophys Sin (Shanghai) ; 51(1): 88-96, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30544157

RESUMO

Propamocarb (PM) is a pesticide that is widely used to protect cucumbers and other plants from downy mildew. Recently, some studies indicated that PM exposure had potential toxic effects in animals. In this study, adult male zebrafish were exposed to 100 and 1000 µg/l PM for 7 days to assess its effects on metabolism and the gut microbiota. We observed a significant decrease in triglyceride (TG) in the livers of zebrafish that were exposed to 1000 µg/l PM for 7 days. At the same time, some genes related to glycolysis and lipid metabolism in the livers of zebrafish, including hexokinase-1 (HK1), pyruvate kinase (PK), acyl-CoA oxidase (Aco), peroxisome proliferator activated receptor alpha (Ppar-α), apolipoprotein A-IV-like (Apo), Acetyl CoA carboxylase-1 (Acc1), diacylglycerol acyltransferase (Dgat), and fatty acid synthase (Fas), were also decreased significantly after PM exposure. Based on GC-MS metabolomics analysis, a total of 48 metabolites changed significantly in the 1000 µg/l PM treatment group in comparison with the control group. These altered metabolites were mainly associated with the glycolysis, amino acid metabolism, and lipid metabolism pathways. Interestingly, we further found that the 1000 µg/l PM treatment group also showed significant elevations in Proteobacteria, Bacteroidetes, and Firmicutes at the phylum level. Sequencing of the 16S rRNA gene in the V3-V4 region also showed a significant change in the abundance and diversity of the gut microbiota in the 1000 µg/l PM treatment group. Our results indicated that exposure to PM for a short time could induce hepatic metabolic disorders and gut microbiota dysbiosis in adult male zebrafish.


Assuntos
Carbamatos/toxicidade , Disbiose/fisiopatologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Doenças Metabólicas/fisiopatologia , Animais , Bactérias/classificação , Bactérias/genética , Disbiose/induzido quimicamente , Disbiose/genética , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/genética , Metabolômica/métodos , RNA Ribossômico 16S/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Tempo , Testes de Toxicidade , Peixe-Zebra
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