maneb and mancozeb

The purpose of this literature review is to document what has already been scientifically published about the pesticide Mancozeb and its potential systemic complications.. Data were collected during the months of July, August and September 2020, from the Medline and PubMed databases, in the Portuguese, English and Spanish, covering articles written in the last 20 years. Twenty-one studies were selected for analysis.. The results found in this review study, indicate that Mancozeb is potentially damaging to health, appearing as an increase in ethylethiourea (ETU) dosages in most studies.. About the widespread use of Mancozeb, the studies found show that this fungicide is a potential cause of several health problems, mainly hepatic, renal and genotoxic, demonstrating with an increase in ETU dosages, as well as liver enzymes in most studies, corroborating the idea that the deliberate use of the product can induce potential systemic complications, and is a public health problem.

Topics: Animals; Fungicides, Industrial; Humans; Maneb; Zineb

Mancozeb is a widely used fungicide approved for use in agriculture in many countries with long persistence in the environment and consequent bioaccumulation in tissues and biological fluids. Despite the large amount of studies published in recent years, the relationship between mancozeb exposure and female reproductive health is not fully elucidated. In order to summarize current evidence on mancozeb exposure and female reproductive disease, we performed a systematic review of literature. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to make this review. An adapted version of the National Toxicology Program's Office of Health and Assessment and Translation (OHAT) framework was used to evaluate the risk of bias. Electronic search on two databases (PubMed and Scopus) was used to find experimental studies (in vitro and in vivo) on mancozeb exposure. The database search identified 250 scientific articles, 20 of which met our inclusion criteria. Selected data were then reviewed and summarized in tables. Overall, mancozeb represents a hazard for female reproductive health, with different mechanisms of action. Undoubtedly more experimental and epidemiological studies are required to definitively validate mancozeb as reproductive toxicant.

Topics: Animals; Cattle; Chick Embryo; Female; Fungicides, Industrial; Humans; Maneb; Mice; Models, Theoretical; Pregnancy; Rabbits; Rats; Rats, Wistar; Reproduction; Reproductive Health; Zineb

The potential adverse reproductive and developmental effects of Mancozeb, especially in sensitive subpopulations, have not been fully reviewed for this widely used fungicide.. To review the experimental and epidemiologic evidence for the association between exposure to Mancozeb and reproductive and developmental health outcomes using an adaptation of the National Toxicology Program's Office of Health Assessment and Translation (OHAT) systematic review framework.. Four databases (PubMed, TOXNET, Web of Science, Google Scholar) were searched for published studies on Mancozeb. Of 403 identified articles, 30 met our inclusion criteria for systematic review.. Results from in vitro studies provide evidence that Mancozeb may indirectly disrupt or impair reproduction at the cellular level and should be regarded as a reproductive toxicant. Animal studies confirm reproductive and developmental toxicity in mammals and suggest that males chronically exposed to Mancozeb experience significant changes in physiological, biochemical, and pathological processes that may lead to infertility. Epidemiological studies were limited to indirect methods of exposure assessment and examined the effect of fungicides more broadly during pre-conception, pregnancy, and birth, yielding mixed results.. High confidence ratings from in vitro and animal studies, in combination with moderate confidence ratings from epidemiologic studies employing indirect methods of exposure assessment, provide evidence that Mancozeb should be regarded as a suspected developmental hazard and a presumed reproductive hazard in humans. More population-based studies linking direct measures and/or biomarkers of exposure to adverse effects on male and female fertility, as well as in utero and early life development, are needed to improve the quality of the evidence base concerning the human reproductive and developmental consequences of Mancozeb exposure.

Topics: Animals; Environmental Exposure; Female; Fertility; Fetal Development; Fungicides, Industrial; Humans; Legislation, Drug; Male; Maneb; Pregnancy; Reproduction; Zineb

Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroidogenic effects have been extensively studied and the mechanisms of toxicity clarified also at molecular level. For many others, information is restricted to few epidemiological data and in vivo/in vitro experiments with animal models. This is the case of the dithiocarbamates, and in particular of the fungicide mancozeb, an ethylenedithiocarbamate widely used to protect fruit and vegetables, ginseng included, because of its low acute toxicity in humans. Although the mechanism(s) by which mancozeb may specifically act on female reproductive organs are largely unknown, data on experimental animals in vivo have demonstrated that the fungicide can induce several disturbances on estrus cycle. When used in vitro at concentrations considered too low to cause human health injuries, the fungicide impairs mouse embryo development and meiotic spindle assembly. The possibility that the female germ cell (the oocyte) could be a specific target of mancozeb suggests a role for this fungicide as probable inductor of infertility also in exposed human populations.

Topics: Animals; Endocrine Disruptors; Environmental Exposure; Female; Humans; Infertility, Female; Maneb; Ovary; Thiocarbamates; Zineb

The worldwide and intensive use of phytosanitary compounds results in environmental and food contamination by chemical residues. Human exposure to multiple pesticide residues is a major health issue. Considering that the liver is not only the main organ for metabolizing pesticides but also a major target of toxicities induced by xenobiotics, we studied the effects of a mixture of 7 pesticides (chlorpyrifos-ethyl, dimethoate, diazinon, iprodione, imazalil, maneb, mancozeb) often detected in food samples. Effects of the mixture was investigated using metabolically competent HepaRG cells and human hepatocytes in primary culture. We report the strong cytotoxicity of the pesticide mixture towards hepatocytes-like HepaRG cells and human hepatocytes upon acute and chronic exposures at low concentrations extrapolated from the Acceptable Daily Intake (ADI) of each compound. Unexpectedly, we demonstrated that the manganese (Mn)-containing dithiocarbamates (DTCs) maneb and mancozeb were solely responsible for the cytotoxicity induced by the mixture. The mechanism of cell death involved the induction of oxidative stress, which led to cell death by intrinsic apoptosis involving caspases 3 and 9. Importantly, this cytotoxic effect was found only in cells metabolizing these pesticides. Herein, we unveil a novel mechanism of toxicity of the Mn-containing DTCs maneb and mancozeb through their metabolization in hepatocytes generating the main metabolite ethylene thiourea (ETU) and the release of Mn leading to intracellular Mn overload and depletion in zinc (Zn). Alteration of the Mn and Zn homeostasis provokes the oxidative stress and the induction of apoptosis, which can be prevented by Zn supplementation. Our data demonstrate the hepatotoxicity of Mn-containing fungicides at very low doses and unveil their adverse effect in disrupting Mn and Zn homeostasis and triggering oxidative stress in human hepatocytes.

Topics: Apoptosis; Ethylenes; Fungicides, Industrial; Hepatocytes; Homeostasis; Humans; Maneb; Manganese; Oxidative Stress; Pesticides; Zinc; Zineb

Topics: Animals; Carnitine; Male; Maneb; Rats; Rats, Wistar; Reflex, Startle

The high abundance of antibiotic resistance genes (ARGs) in the fungicide residual environment, posing a threat to the environment and human health, raises the question of whether and how fungicide promotes the prevalence and dissemination of antibiotic resistance. Here, we reported a novel mechanism underlying bidirectional regulation of a typical heavy-metal-containing fungicide mancozeb on the horizontal transfer of ARGs. Our findings revealed that mancozeb exposure significantly exerted oxidative and osmotic stress on the microbes and facilitated plasmid-mediated ARGs transfer, but its metallic portions (Mn and Zn) were potentially utilized as essential ions by microbes for metalating enzymes to deal with cellular stress and thus reduce the transfer. The results of transcriptome analysis with RT-qPCR confirmed that the expression levels of cellular stress responses and conjugation related genes were drastically altered. It can be concluded mancozeb bidirectionally regulated the ARGs dissemination which may be attributed to the diverse effects on the microbes by its different portions. This novel mechanism provides an updated understanding of neglected fungicide-triggered ARGs dissemination and crucial insight for comprehensive risk assessment of fungicides.

Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Fungicides, Industrial; Genes, Bacterial; Humans; Maneb; Metals, Heavy; Zineb

The toxic potential of dithiocarbamates fungicides widely used in world agriculture is well known, among which Mancozeb is one of the most used. This study aimed to evaluate the toxicity of Mancozeb, determining the LC50% of the product and the behavioral and histological changes observed in fish of the Pacamã species through acute and sublethal toxicity tests. The first experiment was carried out on Pacamã fingerlings exposed to dosages of 0.5, 1, 2, 4, and 8mg/L of Mancozeb under the form ManzateWG®, for a total period of 96 hours in the acute experiment, and in the second experiment, fish were subjected to concentrations of 1/10 of those used in the acute experiment (0.05, 0.1, 0.2, 0.4 and 0.8mg/L, respectively), for 15 days in total. The 50% lethal concentration of ManzateWG® was calculated at the end of the acute experiment, presenting a value of 2.29mg/L at 96h for Pacamã fingerlings. A behavioral assessment was carried out through daily observation of the fish during both experiments, and an increase in mucus production was observed, as well as atypical social behavior in those exposed to the toxic agent. Histopathological evaluation was performed on livers collected after the end of the sublethal experiment, and the main hepatic alterations observed were cytoplasmic vacuolization, inflammatory infiltrate, and necrosis. Mancozeb has toxic potential and is capable of generating behavioral changes, as well as increasing the risk of liver damage in Pacamãs exposed to this compound.

Topics: Animals; Catfishes; Fungicides, Industrial; Maneb; Toxicity Tests; Zineb

Topics: Colorimetry; Fluorescein; Fluorometry; Maneb; Metal Nanoparticles; Silver; Zineb

A novel, rapid and simple reverse-phase high performance liquid chromatography (RP-HPLC) method for the simultaneous determination of three pesticides - mancozeb, azoxystrobin and difenoconazole by derivatization with ethyl iodide is presented. Analysis was performed on a C18 column (Agilent Eclipse plus, 150 mm × 4.6 mm; 5 μ) with the mobile phase consisting of acetonitrile + methanol (90 + 10 v/v) - water (0.1% v/v trifluoroacetic acid) (60 : 40, v/v) pumped isocratically at a flow rate of 1.0 mL min

Topics: Chromatography, High Pressure Liquid; Dioxolanes; Maneb; Pesticides; Pyrimidines; Strobilurins; Triazoles; Zineb

Mancozeb is a fungicide of the ethylene bisdithiocarbamate (EBDC) class complexed to the metals manganese and zinc. Nabam is the sodium salt of the EBDC backbone. The purpose of this study was to determine if these EBDC compounds alter essential metal homeostasis and glutathione status in Sprague-Dawley rats. Our findings indicate EBDCs caused accumulation of copper in kidneys, but not liver. EBDC compounds also increased glutathione reductase activity in liver, but not kidneys, whereas only mancozeb increased glutathione peroxidase activity in the liver. Mancozeb and nabam increased total glutathione in liver, but only mancozeb increased total glutathione in the kidney. Neither mancozeb nor nabam altered glutathione ratio in either liver or kidney compared to control. Our data suggest that the EBDC backbone of mancozeb, and not the zinc or manganese moieties, is responsible for changes in glutathione status and alteration of essential metal homeostasis in rat liver and kidney.

Topics: Animals; Ethylenebis(dithiocarbamates); Ethylenes; Fungicides, Industrial; Glutathione; Kidney; Liver; Maneb; Manganese; Metals; Rats; Rats, Sprague-Dawley; Zinc; Zineb

Mancozeb (MCZ) is widely used as a protective fungicide. This study aimed to explore the effects of low level MCZ exposure on ovary in mice. Twenty Kunming mice were randomly divided into control and MCZ groups (10 mice each). The mice in the MCZ group were given 100 mg/kg MCZ daily via gavage. The mice were sacrificed to collect serum and ovaries on day 31. The experimental indicators were then assessed. The weight of MCZ-exposed mice significantly reduced while ovarian index significantly increased compared with the control group. The FSH, LH, E2, P, CAT, SOD and MDA contents in the serum were significantly decreased and the content of estradiol significantly increased after MCZ exposure. Histological observation showed that the ovarian structure of mice exposed to MCZ was damaged, and the apoptosis was increased. Immunohistochemistry and RT-qPCR showed that the expression of Bax, caspase-3 and caspase-9 significantly increased in the MCZ- group. Conversely, Bcl-2 expression significantly decreased. Transcriptome sequencing showed that the expression of NADH dehydrogenase ND3, ND4L, ND6 subunits, Cyt b, and SDHC genes in mitochondria were down-regulated after MCZ exposure, similar to real-time PCR analysis. These results collectively indicate that the MCZ can affect the abnormal function of mitochondrial respiratory chain, lead to oxidative phosphorylation decoupling, produce oxidative stress, and finally cause ovarian injury and apoptosis in mice.

Topics: Animals; Apoptosis; Female; Maneb; Mice; Ovary; Oxidative Stress; Zineb

Mancozeb is a broad-spectrum fungicide used extensively in agriculture to protect plants from numerous diseases. Hemolysis of human erythrocytes on exposure to mancozeb has been reported. In the present study, we investigated the interaction of mancozeb with human hemoglobin (Hb) using multi-spectroscopic techniques, molecular docking and molecular dynamic simulation. UV-visible spectroscopy studies suggested intimate binding of mancozeb to Hb. Mancozeb quenched the intrinsic fluorescence of Hb and Stern-Volmer plots revealed that the quenching mechanism was of static type. Evaluation of thermodynamic parameters indicated that the binding of Hb to mancozeb was spontaneous, with van der Waals forces and hydrogen bonding being the key contributors in the binding reaction. Synchronous fluorescence experiments demonstrated that mancozeb altered the microenvironment around tryptophan residues, whereas polarity around tyrosine residues was not changed. Circular dichroism studies showed a decrease in the α helical content of Hb upon interaction with mancozeb. The inhibition of esterase activity showed that mancozeb can impair the enzymatic functions of Hb. Molecular docking study revealed that strong binding affinity existed between mancozeb and Hb, with hydrophobic forces playing a crucial role in the interaction. Molecular dynamic simulation showed that mancozeb formed a stable complex with Hb resulting in slight unfolding of the protein. To sum up, the results of this study show that mancozeb binds strongly to Hb, induces conformational changes in Hb and adversely affects its function.

Topics: Binding Sites; Circular Dichroism; Hemoglobins; Humans; Maneb; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Binding; Spectrometry, Fluorescence; Thermodynamics; Zineb

To evaluate the histopathological, immunohistochemical, and biochemical effects of liver changes after mancozeb administration.. Rats were divided into groups-the control group (n=7) and the mancozeb group (n=7)-, given 500 mg/kg mancozeb dissolved in corn oil daily for four weeks by an orogastric tube. Caspase-3 and tumor necrosis factor-alpha (TNF-α) primary antibodies were used for immunohistochemical analysis.. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the mancozeb group increased significantly than ones of the control group. Venous dilatation, inflammation, hepatocyte degeneration, TNF-α, and caspase-3 expression scores increased significantly in the mancozeb group. In the mancozeb group, intensive caspase-3 expression was observed in hepatocyte cells around the central vein in the center of the liver lobule, and there was an increase in TNF-α expression in the inflammatory cells around the enlarged central vein and Kupffer cells and apoptotic hepatocyte cells.. Subacute mancozeb exposure in rats leads to elevated toxicity with impaired liver function, increased inflammation in tissue and increased apoptosis due to cellular damage in the liver, and decreased liver regeneration ability due to congestion and degeneration of blood vessels.

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; Caspase 3; Fungicides, Industrial; Inflammation; Liver; Liver Diseases; Maneb; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Zineb

Fungicides make up the largest part of total pesticide use, with the dithiocarbamate mancozeb being widely applied as a nonsystemic contact pesticide to protect a wide range of field crops against fungal diseases. Although nematodes are key drivers of soil functioning, data on effects of fungicides, and especially mancozeb, on these nontarget organisms are scarce. Therefore, the effects of mancozeb on a soil nematode community from a natural grassland were assessed in small-scale soil microcosms. Nematodes were exposed to mancozeb-spiked soil in six nominal concentrations (7-133 mg/kg dry soil) and analyzed after 14, 56, and 84 days in terms of densities, genus composition, and functional traits. Because this fungicide is known to quickly degrade in soils (50% degradation time <1 day), mancozeb concentrations were analyzed for all sampling occasions. Chemical analysis revealed considerably lower measured concentrations compared with the aimed nominal soil concentrations at the beginning of the exposure (1-18 mg/kg dry soil), suggesting fast degradation during the spiking process. Nevertheless, the native nematode community responded sensitively to the fungicide mancozeb, revealing lower no-observed-effect concentration and 10% effect concentration (EC10) values than reported for other soil invertebrates such as springtails and earthworms. Using the EC10 for the most sensitive nematode community endpoint (percentage of predators and omnivores: 1.2 mg/kg dry soil), the risk assessment exhibited a toxicity exposure ratio of 0.66 and, thus, a high risk of mancozeb for soil nematodes. Keeping in mind their abundance and their central roles in soil food-web functioning, the demonstrated sensitivity to a widely applied fungicide underscores the relevance of the inclusion of nematodes into routine risk-assessment programs for pesticides. Environ Toxicol Chem 2022;41:2420-2430. © 2022 SETAC.

Topics: Animals; Fungicides, Industrial; Grassland; Maneb; Nematoda; Soil; Zineb

Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p < 0.05). Our results suggest that AMPK and mitogen‑activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ.

Topics: AMP-Activated Protein Kinases; Animals; Liver; Maneb; Metabolomics; Mice; Transcriptome; Zineb

Mancozeb (MNZ) is a fungicide commonly employed in many countries worldwide. This study assesses MNZ absorption dynamics in 19 greenhouse farmers, specifically following dermal exposure, aiming to verify the efficacy of both preventive actions and protective equipment. For data collection, a multi-assessment approach was used, which included a survey to record study population features. MNZ exposure was assessed through the indirect measurement of ethylene thiourea (ETU), widely employed as an MNZ biomarker. The ETU concentration was measured with the patch method, detecting environmental ETU trapped in filter paper pads, applied both on skin and working clothes, during the 8 h work shift. Urine and serum end-of-shift samples were also collected to measure ETU concentrations and well-known oxidative stress biomarkers, respectively, namely reactive oxygen metabolites (ROMs), advanced oxidation protein products (AOPPs), and biological antioxidant potential (BAP). It was observed that levels of ETU absorbed and ETU excreted were positively correlated. Additionally, working clothes effectively protected workers from MNZ exposure. Moreover, following stratification of the samples based on the specific working duty (i.e., preparation and spreading of MNZ and manipulation of MNZ-treated seedlings), it was found that the spreading group had higher ETU-related risk, despite lower chronic exposure levels. AOPP and ROM serum levels were higher in MNZ-exposed subjects compared with non-exposed controls, whereas BAP levels were significantly lower. Such results support an increase in the oxidative stress upon 8 h MNZ exposure at work. In particular, AOPP levels demonstrated a potential predictive role, as suggested by the contingency analysis results. Overall, this study, although conducted in a small group, confirms that ETU detection in pads, as well as in urine, might enable assessment of the risk associated with MNZ exposure in greenhouse workers. Additionally, the measurement of circulating oxidative stress biomarkers might help to stratify exposed workers based on their sensitivity to MNZ. Pivotally, the combination of both ETU measurement and biological monitoring might represent a novel valuable combined approach for risk assessment in farmhouse workers exposed to pesticides. In the future, these observations will help to implement effective preventive strategies in the workplace for workers at higher risk, including greenhouse farmers who are exposed to pesti

Topics: Advanced Oxidation Protein Products; Biomarkers; Ethylenethiourea; Farmers; Humans; Maneb; Occupational Exposure; Oxidative Stress; Pesticides; Zineb

We developed phospho-ERK1/2 ELISA for human and rainbow trout liver cells, employing HepG2 and RTL-W1 cell lines as models. The assay was applied to detect changes in ERK1/2 activity for nine chemicals, added over a wide concentration range and time points. Cell viability was measured to separate ERK1/2 regulation from cytotoxicity. Perfluorooctane sulfonate and carbendazim did not change ERK1/2 activity; influence on ERK1/2 due to cytotoxicity was indicated for tributyltin and cypermethrin. Mancozeb, benzo[a]pyrene, and bisphenol A stimulated ERK1/2 up to ∼2- (HepG2) and 1.5 (RTL-W1)-fold, though the kinetics differed between chemicals and cell lines. Bisphenol A and benzo[a]pyrene were the most potent concentration-wise, altering ERK1/2 activity in pM (HepG2) to nM (RTL-W1) range. While atrazine and ibuprofen increased ERK1/2 activity by ∼2-fold in HepG2, they did not initiate an appreciable response in RTL-W1. This assay proved to be a sensitive, medium- to high-throughput tool for detecting unrecognized ERK1/2-disrupting chemicals.

Topics: Alkanesulfonic Acids; Animals; Atrazine; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Carbamates; Cell Line; Cell Survival; Fluorocarbons; Humans; Ibuprofen; Liver; Maneb; MAP Kinase Signaling System; Oncorhynchus mykiss; Phenols; Phosphorylation; Pyrethrins; Trialkyltin Compounds; Water Pollutants, Chemical; Zineb

Mancozeb (MZ), an antibacterial pesticide, has been linked to reproductive toxicity, neurotoxicity, and endocrine disruption. However, whether MZ has cardiactoxicity is unclear. In this study, the cardiotoxic effects of exposure to environment-related MZ concentrations ranging from 1.88 μM to 7.52 μM were evaluated at the larval stage of zebrafish. Transcriptome sequencing predicted the mechanism of MZ-induced cardiac developmental toxicity in zebrafish by enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Consistent with morphological changes, the osm, pfkfb3, foxh1, stc1, and nrarpb genes may effect normal development of zebrafish heart by activating NOTCH signaling pathways, resulting in pericardial edema, myocardial fibrosis, and congestion in the heart area. Moreover, differential gene expression analysis indicated that cyp-related genes (cyp1c2 and cyp3c3) were significantly upregulated after MZ treatment, which may be related to apoptosis of myocardial cells. These results were verified by real-time quantitative RT-qPCR and acridine orange staining. Our findings suggest that MZ-mediated cardiotoxic development of zebrafish larvae may be related to the activation of Notch and apoptosis-related signaling pathways.

Topics: Animals; Embryo, Nonmammalian; Gene Expression Profiling; Maneb; Transcriptome; Water Pollutants, Chemical; Zebrafish; Zineb

Mancozeb (MZB) is a worldwide fungicide for the management of fungal diseases in agriculture and industrial contexts. Human exposure occurs by consuming contaminated plants, drinking water, and occupational exposure. There are reports on MZB's reprotoxicity such as testicular structure damage, sperm abnormalities, and decrease in sperm parameters (number, viability, and motility), but its molecular mechanism on apoptosis in testis remains limited. To investigate the molecular mechanisms involved in male reprotoxicity induced by MZB, we used primary cultures of mouse Sertoli-germ cells. Cells were exposed to MZB (1.5, 2.5, and 3.5 μM) for 3 h to evaluate viability by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, reactive oxygen species (ROS) generation, and oxidative stress parameters (lipid peroxidation). Cell death and mitogen-activated protein kinase (MAPK) signaling were measured in these cells using flow cytometry and western blotting. In addition, some groups were exposed to

Topics: Animals; Apoptosis; Germ Cells; Male; Maneb; Mice; Mitogen-Activated Protein Kinases; Oxidative Stress; Sertoli Cells; Zineb

As agriculture expands to provide food and wellbeing to the world's growing population, there is a simultaneous increasing concern about the use of agrochemicals, which can harm non-target organisms, mainly in the aquatic environment. The fungicide Mancozeb (MZ) has been used on a large-scale and is a potent inducer of oxidative stress. Therefore, there is an urgent need for the development of more sensitive biomarkers designed to earlier biomonitoring of this compound. Here we tested the hypothesis that behavioral changes induced by sublethal MZ concentrations would occur first as compared to biochemical oxidative stress markers. Embryos at 4 h post-fertilization (hpf) were exposed to Mancozeb at 5, 10 and 20 μg/L. Controls were kept in embryo water only. Behavioral and biochemical parameters were evaluated at 24, 28, 72, and 168 hpf after MZ exposure. The results showed that MZ significantly altered spontaneous movement, escape responses, swimming capacity, and exploratory behavior at all exposure times. However, changes in ROS steady-stead levels and the activity of antioxidant enzymes were observable only at 72 and 168 hpf. In conclusion, behavioral changes occurred earlier than biochemical alterations in zebrafish embryos exposed to MZ, highlighting the potential of behavioral biomarkers as sensitive tools for biomonitoring programs.

Topics: Animals; Embryo, Nonmammalian; Maneb; Oxidation-Reduction; Oxidative Stress; Zebrafish; Zineb

Mancozeb is a metal-containing ethylene bis-dithiocarbamate fungicide widely used in agriculture. Ethylene thiourea (ETU) is the primary metabolite of Mancozeb. Mancozeb has been associated with spontaneous abortions and abnormal menstruation in women. However, the effects of Mancozeb and ETU on embryo attachment remain unknown. The human blastocyst surrogate trophoblastic spheroids (JEG-3), endometrial epithelial surrogate adenocarcinoma cells (Ishikawa), or human primary endometrial epithelial cells (EECs) monolayer were used in the spheroid attachment models. Ishikawa and EECs were pretreated with different concentrations of Mancozeb or ETU for 48 h before the attachment assay. Gene expression profiles of Ishikawa cells were examined to understand how Mancozeb modulates endometrial receptivity with Microarray. The genes altered by Mancozeb were confirmed by qPCR and compared with the ETU treated groups. Mancozeb and ETU treatment inhibited cell viability at 10 μg/mL and 5000 µg/mL, respectively. At non-cytotoxic concentrations, Mancozeb at 3 μg/mL and ETU at 300 μg/mL reduced JEG-3 spheroid attachment onto Ishikawa cells. A similar result was observed with human primary endometrial epithelial cells. Mancozeb at 3 μg/mL modified the transcription of 158 genes by at least 1.5-fold in Microarray analysis. The expression of 10 differentially expressed genes were confirmed by qPCR. Furthermore, Mancozeb decreased spheroid attachment possibly through downregulating the expression of endometrial estrogen receptor β and integrin β3, but not mucin 1. These results were confirmed in both overexpression and knockdown experiments and co-culture assay. Mancozeb but not its metabolite ETU reduced spheroid attachment through modulating gene expression profile and decreasing estrogen receptor β and integrin β3 expression of endometrial epithelial cells.

Topics: Blastocyst; Cell Adhesion; Cell Line, Tumor; Cell Survival; Coculture Techniques; Down-Regulation; Endometrium; Epithelial Cells; Estrogen Receptor beta; Female; Fungicides, Industrial; Gene Expression; Gene Knockdown Techniques; Humans; Integrin beta3; Maneb; Pregnancy; Spheroids, Cellular; Zineb

Ethylene bisdithiocarbamate pesticides, including Mancozeb (MZ), are used as fungicides. Effects of MZ on apoptosis induction and mitochondrial activity of HT-29 colon cells were investigated. MZ exposed cells exhibited blebbing and cellular membrane disruption in scanning electron micrographs. Positive fluorescent staining with Annexin V at doses of 60-140 μM supports apoptosis as the mechanism of cell death. Activity of all electron transport chain complexes were evaluated. Mitochondrial Complex I activity was decreased in 100 μM treated cells. Mitochondrial Complex III activity was decreased in 60 and 100 μM MZ treated cells. Mitochondrial Complex II and Complex IV activities were decreased in cells treated with 60, 100, and 140 μM. Cells treated with 60 μM exhibited a decrease in Complex V enzyme activity. It is concluded that MZ exposure inhibits all mitochondrial complexes of HT-29 cells and that positive fluorescent microscopy and blebbing support previous studies of cell death via apoptosis.

Topics: Apoptosis; Cell Survival; Colon; Electron Transport Chain Complex Proteins; Fungicides, Industrial; HT29 Cells; Humans; Maneb; Mitochondria; Zineb

Multiple and consecutive application of fungicide might damage the rhizosphere bacterial community of citrus. In order to evaluated effect of mancozeb on the chemical properties of citrus-cultivated soil and the richness and diversity of rhizosphere bacterial community. The abundance response of rhizosphere bacterial groups without application or with application of 1.333 g mg

Topics: Bacteria; Citrus; Maneb; Rhizosphere; Soil; Soil Microbiology; Zineb

Antifungal activity of Monotheca buxifolia methanolic extract and its various fractions were assessed against Macrophomina phaseolina, a soil-borne fungal pathogen of more than 500 vegetal species as well as rare and emerging opportunistic human pathogen. Different concentrations of methanolic extract (3.125 to 200 mg mL

Topics: Antifungal Agents; Ascomycota; Humans; Maneb; Mycoses; Opportunistic Infections; Pentacyclic Triterpenes; Plant Extracts; Zineb

Negative impacts on amphibians have been reported due to contamination by agrochemicals. However, until now, no study has tested the effect of the fungicide mancozeb (MZ) on thermal tolerance and its relationship with the expression of heat shock proteins (HSPs). MZ is the best-selling broad-spectrum fungicide in the world, which negatively affects non-target organisms. Here, we tested for the first time the effects of MZ on critical thermal maximum (CTmax) and its relationship to the expression of heat shock protein 70 (HSP70) in tadpoles of Physalameus henselii, a colder-adapted species in southernmost of the Neotropical region. A sublethal concentration of 2 mg/L was used. We found that the CTmax of the MZ-treated group was lower than that of the control group. In addition, there was an increase in HSP70 expression in tadpoles exposed to MZ and in tadpoles that underwent heat treatment. However, tadpoles subjected to MZ and heat treatment showed no induced HSP70 protein expression. Our results demonstrated that sublethal doses of the fungicide MZ negatively affected the thermal physiology and heat shock protein expression in tadpoles of P. henselii by inducing an increase in HSP70 concentration and by reducing the critical CTmax supported by tadpoles. It is important to understand the relationship between environmental contamination and physiological thermal limits in our current scenario of high rates of habitat conversion associated with unrestricted use of agrochemicals, as well as the challenging environmental changes induced by global warming.

Topics: Animals; Anura; Fungicides, Industrial; HSP70 Heat-Shock Proteins; Larva; Maneb; Reptilian Proteins; Thermotolerance; Zineb

Apple scab is one of the most economically important diseases of apple in temperate production regions. In the absence of durable host resistance in commercially preferred cultivars, considerable applications of fungicides are needed to manage this disease. With the sequential development of resistance to nearly all classes of single-site fungicides in the apple scab pathogen

Topics: Ascomycota; Bacillus subtilis; Biological Control Agents; Captan; Fungicides, Industrial; Malus; Maneb; Norbornanes; Plant Diseases; Pyrazoles; Zineb

Mancozeb is classified as an endocrine disruptor; thus the present study was carried out to investigate the impact of mancozeb on mammalian ovarian functions using in vitro caprine oocyte maturation and granulosa cell culture models. Caprine cumulus oocyte complexes (COCs) and granulosa cells were cultured under standard culture conditions and treated with mancozeb concentrations of 0.3, 3, and 30 μg/ml along with a control for 24 h and assessed. Granulosa cell viability and progesterone concentration in spent culture media after treatments were also assessed. Mancozeb significantly decreased (P < 0.05) the oocytes cumulus expansion and the maturation of caprine oocytes. Marked changes in granulose cell morphology were observed with 30 μg/ml mancozeb and significantly reduced (P < 0.05) cell viability. Interestingly, the same concentrations significantly increased (P < 0.05) the progesterone secretion by the cells. Significant reduction of granulosa cells viability and reduction of cumulus expansion and suppression of metaphase plate formation in oocyte can impair the fertilization ability and developmental potential of the oocytes. High progesterone concentration due to mancozeb treatment may suppress LH surge and suppress ovulation. In conclusion, mancozeb suppresses granulosa cells viability, reduces cumulus expansion, and suppresses metaphase plate formation but induces progesterone secretion from granulosa cells that may inhibit LH surge for ovulation process.

Topics: Animals; Female; Fungicides, Industrial; Goats; Granulosa Cells; Maneb; Oocytes; Zineb

Mancozeb (MZ) and zoxamide (ZOX) are fungicides commonly used in pest control programs to protect vineyards. Their toxic and genotoxic potential were investigated in vitro on HepG2 and A549 cell lines at environmentally relevant concentrations. Cytotoxicity, apoptosis, necrosis and intracellular reactive oxygen species (ROS), comet assay and a micronucleus test with CREST immunofluorescence were used. The expression of a panel of genes involved in apoptosis/necrosis (

Topics: Amides; Comet Assay; DNA Damage; Fungicides, Industrial; Maneb; Oxidative Stress; Reactive Oxygen Species; Zineb

Apple scab, caused by

Topics: Ascomycota; Benchmarking; Malus; Maneb; Plant Diseases; Plant Leaves; South Africa; Zineb

The cross regulation between neuroendocrine system, particularly Hypothalamus-Pituitary-Thyroid (HPT) axis and immune system during embryonic/early neonatal developmental stages shapes the functional attribute of immune response throughout the life. Thus, disruption of immune system was anticipated on exposure to thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and fipronil (FPN) during critical windows of early postnatal days (PND) development.. Mice were exposed to MCZ and FPN as individual (0.5% LD 50 each) and as mixtures (0.25% and 0.5% LD 50 each) from PND 31 (initiation phase of immune response) till PND 60 (Maturation phase). Thyroxine (T4) supplementation was given from PND 51 to PND 60. Assessment was done at PND 61 as well as at PND 91 (adults).. Plasma level of thyroid hormones (T3 and T4) was reduced but pituitary hormone (TSH) increased till adulthood on exposure to mixture pesticides but not on individual exposure. Mixture pesticides also increased body weight gain and reduced survival rate in adults. Exposure of individual pesticides exert immunotoxicity but more pronounced immune suppression was observed in mixture pesticides exposed group as reflected in reduced relative weight and cellularity in spleen and thymus, reduced in vitro mitogenic (Con A/LPS) response of splenocytes and thymocytes (reduced proliferative index and increased apoptotic/necrotic death). T4 supplementation ameliorated thyroid disruptive and immunotoxic effect of pesticides.. The additive/synergistic toxicity as well as hypothyroidism induced by mixture pesticides has produced pronounced immune suppression that reflected till adulthood. Supplementation of T4 prevented thyroid axis disruption mediated immunosuppression.

Topics: Animals; Body Weight; Endocrine Disruptors; Female; Fungicides, Industrial; Immune System; Insecticides; Male; Maneb; Mice; Organ Size; Pesticides; Pyrazoles; Spleen; Survival Analysis; Thymus Gland; Thyroxine; Zineb

Dithiocarbamates (DTCs) like mancozeb (MZ) and disulfiram (DS) are used throughout agriculture and medicine and have been implicated in neurotoxicity. Little research has been studied on the reported myopathies caused by these compounds. Their pathogenesis and mechanism of muscle toxicity has not been fully studied. The aim of this study is to investigate if DTCs alter striated muscle tissues in vivo. Long-Evans rats were treated with either MZ or DS followed by analysis of muscle biomarkers and metal levels. DS resulted in increases in serum lactate dehydrogenase (LDH), cardiac troponin, and myoglobin levels. Creatine kinase-MB serum levels decreased. Mancozeb only showed an increase in serum LDH. Both MZ and DS-treatment resulted in altered metal levels in the myocardium but not skeletal muscle. Ultrastructural alterations included damaged mitochondria and myofibril splitting. The presence of multivesicular bodies, and alterations of the intercalated disc were also seen.

Topics: Animals; Biomarkers; Disulfiram; Fungicides, Industrial; Maneb; Muscle, Striated; Muscular Diseases; Rats; Rats, Long-Evans; Zineb

Agricultural activity, especially the increasing use of pesticides, is considered one of the main reasons for the decline of amphibian populations. Mancozeb (MCZ) is one of the most used fungicides worldwide, despite its ancient use and toxicity demonstrated in different taxa. However, there is limited information about the effects of MCZ in amphibians, which are keystones of riparian ecosystems. For species conservation purposes, it is essential to identify the most sensitive developmental period(s) of a given species to a xenobiotic. We evaluated the toxicity of a commercial fungicide of mancozeb, (80% active ingredient) on the early development of the common South American toad Rhinella arenarum (Anura, Bufonidae). Embryos from early blastula (S.4) and larvae from complete operculum (S.25) stages were exposed to a wide range of MCZ concentrations during acute, subchronic and chronic exposure (up to 504 h) periods. The toxicity profiles for lethal and sublethal effects were performed. At all exposure times, MCZ was more toxic to embryos, for instance, NOEC 504 h were 0.01 and 0.05 mg MCZ/L for embryos and larvae, respectively. Thus, embryo sensitivity was 5-fold higher than larvae. A Teratogenic Index of 14 indicated the significant teratogenic potential of this fungicide. Among sublethal effects, embryos exhibited a wide range of abnormalities with high incidence. The ecological risk assessment demonstrated that the estimated Risk Quotient value for Rhinella arenarum embryos at chronic exposure was higher than the Level of Concern value, which warns about the potential risk of MCZ for this native species.

Topics: Animals; Bufo arenarum; Bufo bufo; Bufonidae; Ecosystem; Embryo, Nonmammalian; Fungicides, Industrial; Larva; Maneb; Risk Assessment; Zineb

Growing evidence suggests that pesticide exposure may influence respiratory health, but data in young children are very limited. We examined the association of prenatal pesticide exposure with lower respiratory tract infections (LRTIs) and wheeze at one year of age in children from the Infants' Environmental Health (ISA) study in Costa Rica.. We measured seven pesticide metabolites, including ethylenethiourea (ETU, metabolite of mancozeb), in maternal urine samples collected repeatedly during pregnancy. For each woman, we averaged pesticide concentrations during each half of pregnancy (≤20 and >20 weeks of gestation) and across repeated samples collected over the course of pregnancy. We collected information about LRTIs (n = 355) and wheezing (n = 272) during the first year of life from mothers when their children were 11-19 months old. We fit multivariable logistic regression models using high (quartile 4) vs. low (quartiles 1-3) urinary pesticide concentrations as exposures and adjusted models for maternal age, education, parity, gestational age at birth, and child sex.. Ten percent of the children had at least one LRTI and 39% had at least one episode of wheezing during their first year of life. Median (25-75th percentile) specific gravity-corrected urinary ETU concentrations during the first half, second half, and over the course of pregnancy were 3.4 (2.1-5.0), 3.3 (2.2-4.7), and 3.4 (2.4-5.0) ng/mL, respectively. We observed that high urinary ETU concentrations during the first half of pregnancy were associated with increased odds of LRTI (OR = 2.45; 95% CI: 0.96, 6.26), whereas high urinary ETU concentrations during the second half of pregnancy were associated with decreased odds of wheezing (OR = 0.50; 95% CI: 0.26, 0.96). We found that the association between high urinary ETU concentrations during the first half of pregnancy and LRTIs persisted among mother-child pairs with either high or low ETU concentrations during the second half. In contrast, the association of high urinary ETU concentrations during the second half of pregnancy with wheezing was attenuated when we simultaneously adjusted for urinary ETU concentrations during the first half. We observed null associations between other pesticide metabolites measured during pregnancy and respiratory outcomes.. Our data indicate that exposure to mancozeb/ETU during the first half of pregnancy may be associated with respiratory outcomes in the first year of life.

Topics: Adult; Environmental Pollutants; Ethylenethiourea; Female; Humans; Infant; Infant Health; Male; Maneb; Maternal Exposure; Maternal-Fetal Exchange; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects; Respiratory Sounds; Respiratory Tract Infections; Young Adult; Zineb

Agricultural pesticides are extensively used for weed- and pest control, resulting in residues of these compounds in food. The general population is mainly exposed through dietary intake. Exposure to certain pesticides has been associated with adverse human health outcomes. Our aim was to assess urinary concentrations and temporal trends in the biomarkers of commonly used pesticides. Samples were collected from adolescents (n = 1060) in Scania, Sweden, from 2000 to 2017. Concentrations of 14 pesticide biomarkers were analyzed in urine using LC-MS/MS. Temporal trends in biomarker concentrations (ln-transformed) were evaluated using linear regression. Biomarkers of pyrethroids (3-PBA and DCCA), chlorpyrifos (TCPy), chlormequat (CCC), thiabendazole (OH-TBZ), and mancozeb (ETU) were detected in >90% of the population all sampling years. The biomarkers CCC and TCPy had the highest median concentrations (>0.8 µg/L), whereas the biomarkers of cyfluthrin (4F-3-PBA) and two pyrethroids (CFCA) had the lowest median concentrations (<0.02 µg/L). Increasing temporal trends were found for the biomarkers 3-PBA (3.7%/year), TCPy (1.7%/year) and biomarkers of pyrimethanil (11.9%/year) and tebuconazole (12.2%/year). Decreasing trends were found for CCC (-5.5%/year), OH-TBZ (-5.5%/year), and ETU (-3.9%/year). Our results suggest that Swedish adolescents are commonly exposed to pesticides in low concentrations (median concentrations <3.88 µg/L).

Topics: Adolescent; Agriculture; Benzoates; Biomarkers; Chlorpyrifos; Chromatography, Liquid; Environmental Pollutants; Female; Humans; Male; Maneb; Nitriles; Pesticides; Pyrethrins; Sweden; Tandem Mass Spectrometry; Zineb

The toxicological knowledge of mancozeb (MZ)-containing commercial formulations on non-target species is scarce and limited. Therefore, the objective of this work was to represent a realistic application scenario by evaluating the toxicity of environmental relevant and higher concentrations of a commercial formulation of MZ using zebrafish embryos. Following determination of the 96-h LC

Topics: Animals; Catalase; Embryo, Nonmammalian; Embryonic Development; Maneb; Oxidative Stress; Superoxide Dismutase; Zebrafish; Zineb

The interference in endocrine signaling in particular of hypothyroid-pituitary-thyroid axis during embryonic/neonatal development increases the risk of long-lasting immune dysfunctioning. Anticipating that, environmentally realistic exposure of established thyroid disrupting pesticides of dithiocarbamate group mancozeb and phenylpyrazole fipronil was given to mice as individual and as mixtures (MIX-I/MIX-II) during the critical initiation phase of the immune response from postnatal day (PND) 31 till PND 60 (maturation phase). The direct exposure effect was assessed at PND 61 and the persistent effect was assessed at PND 91. Pronounced oxidative stress/genotoxicity in lymphoid organs at even low dose mixture exposure of pesticides (MIX-I/ MIX-II) continued to suppress the immune system till adulthood; might be due to the synergistic/additive action. The oxidative stress/genotoxicity effect was prevented on T4 supplementation to inhibit immunotoxicity as T4 is an immune enhancer and antioxidants. Oxidative stress/genotoxicity is suggested as a mechanism of thyroid disruption mediated immune suppression.

Topics: Animals; DNA Damage; Female; Male; Maneb; Mice; Oxidative Stress; Pesticides; Pyrazoles; Spleen; Thymus Gland; Thyroid Gland; Zineb

The fungicide Mancozeb is an endocrine-disrupting chemical and the mode of action of Mancozeb on embryo implantation is largely unknown. Mancozeb (1 and 3 μg/ml) significantly reduced Jeg-3 trophoblastic spheroids attachment to endometrial epithelial Ishikawa cells. Mancozeb treatment from gestation day (GD) 1 to GD8 or from GD4 to GD8 significantly lowered the number of implantation sites with higher incidence of morphological abnormalities in the reproductive tissues. However, these were not seen in the treatment from GD1 to GD4. Mancozeb at 30 mg/kg BW/d did not alter the expression of p53, COX-2, or PGFS transcripts in the uterus, but down-regulated the PGES transcript and protein. Mancozeb treatment in human endometrial stromal cells did not alter the decidualization response, but the morphological transformation was impaired. Taken together, exposure to Mancozeb affected embryo implantation probably through the modulation of decidualization and to delineate the exact mode of action needs further investigations.

Topics: Animals; Cell Line; Embryo Implantation; Female; Fungicides, Industrial; Gene Expression Regulation, Developmental; Humans; Male; Maneb; Mice, Inbred ICR; Zineb

Pesticides represent an economical, labor-saving, and efficient tool for pest management, but their intrinsic toxic properties may endanger workers and the general population. Risk assessment is necessary, and biological monitoring represents a potentially valuable tool. Several international agencies propose biological exposure indices (BEI), especially for substances which are commonly absorbed through the skin. Biological monitoring for pesticide exposure and risk assessment seems a natural choice, but biological exposure limits (BEL) for pesticides are lacking. This study aims at establishing equivalent biological exposure limits (EBEL) for pesticides using real-life field data and the Acceptable Operator Exposure Level (AOEL) of mancozeb as the reference. This study included a group of 16 vineyard pesticide applicators from Northern Italy, a subgroup of a more extensive study of 28 applicators. Their exposure was estimated using "patch" and "hand-wash" methodologies, together with biological monitoring of free ethylene-bis-thiourea (ETU) excretion in 24-h pre- and post-exposure urine samples. Modeling was done using univariate linear regression with ETU excretion as the dependent variable and the estimated absorbed dose as the independent variable. The median skin deposition of mancozeb in our study population was 125 μg, leading to a median absorbed dose of 0.9 μg/kg. The median post-exposure ETU excretion was 3.7 μg. The modeled EBEL for mancozeb was 148 μg of free ETU or 697 μg of total ETU, accounting for around 75% of the maximum theoretical excretion based on a mass balance model. Although preliminary and based on a small population of low-exposed workers, our results demonstrate a procedure to develop strongly needed biological exposure limits for pesticides.

Topics: Adult; Biological Monitoring; Ethylenethiourea; Farms; Fungicides, Industrial; Humans; Italy; Male; Maneb; Middle Aged; Occupational Exposure; Risk Assessment; Skin; Skin Absorption; Zineb

The biobed is a purification system, which reduces soil pollution for receiving pesticide residues from handling and washing machinery in agricultural areas. The aims of this study were (1) to assess ecotoxicity effects over time to soil fauna, posed by Lorsban

Topics: Agriculture; Animals; Arthropods; Brazil; Chlorpyrifos; Ecotoxicology; Environmental Pollution; Maneb; Oligochaeta; Pesticide Residues; Pesticides; Soil; Soil Pollutants; Zineb

In this study, the fungicidal activities of the fungicides azoxystrobin, difenoconazole + propiconazole, carbendazim, flutriafol, fluopyram + tebuconazole, mancozeb and thiophanate-methyl against rice blast and dirty panicle pathogens were evaluated under laboratory and field conditions. Mancozeb exhibited the highest level of fungicidal activity against the blast pathogen Pyricularia oryzae, with an EC

Topics: Antifungal Agents; Ascomycota; Benzamides; Benzimidazoles; Carbamates; Dioxolanes; Maneb; Oryza; Plant Diseases; Pyridines; Pyrimidines; Strobilurins; Thailand; Triazoles; Zineb

Cross-resistance, a phenomenon that a pathogen resists to one antimicrobial compound also resists to one or several other compounds, is one of major threats to human health and sustainable food production. It usually occurs among antimicrobial compounds sharing the mode of action. In this study, we determined the sensitivity profiles of Alternaria alternata, a fungal pathogen which can cause diseases in many crops to two fungicides (mancozeb and difenoconazole) with different mode of action using a large number of isolates (234) collected from seven potato fields across China.. We found that pathogens could also develop cross resistance to fungicides with different modes of action as indicated by a strong positive correlation between mancozeb and difenoconazole tolerances to A. alternata. We also found a positive association between mancozeb tolerance and aggressiveness of A. alternata, suggesting no fitness penalty of developing mancozeb resistance in the pathogen and hypothesize that mechanisms such as antimicrobial compound efflux and detoxification that limit intercellular accumulation of natural/synthetic chemicals in pathogens might account for the cross-resistance and the positive association between pathogen aggressiveness and mancozeb tolerance.. The detection of cross-resistance among different classes of fungicides suggests that the mode of action alone may not be an adequate sole criterion to determine what components to use in the mixture and/or rotation of fungicides in agricultural and medical sects. Similarly, the observation of a positive association between the pathogen's aggressiveness and tolerance to mancozeb suggests that intensive application of site non-specific fungicides might simultaneously lead to reduced fungicide resistance and enhanced ability to cause diseases in pathogen populations, thereby posing a greater threat to agricultural production and human health. In this case, the use of evolutionary principles in closely monitoring populations and the use of appropriate fungicide applications are important for effective use of the fungicides and durable infectious disease management.

Topics: Alternaria; China; Dioxolanes; Drug Resistance, Fungal; Fungicides, Industrial; Maneb; Plant Diseases; Solanum tuberosum; Triazoles; Zineb

Mancozeb (Manganese ethylene bis-dithiocarbamate with zinc salt) is a dithiocarbamate fungicide used to control fungal disease in many fruit plants, flowers and the maintenance of field crops. The effect of mancozeb on cell viability of human gastric adenocarcinoma AGS, SNU-1 cells and human normal FHs 74 Int cells were investigated. This study demonstrated that mancozeb was able to inhibit cell proliferation by 56-82% at 5-10 μM concentrations after 48 h. Mancozeb treatment for 48 h resulted in 33% (P < 0.05) and 61% (P < 0.001) increase in apoptotic cells at 5 and 10 μM concentrations in AGS cells, respectively. Treatment with mancozeb did not cause cell cycle arrest, while modulated the expression level of cleaved caspase-3, and cleavage of poly-(ADP-ribose) polymerase. Furthermore, treatment with mancozeb caused a rapid stimulation of reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential. The results also showed that mancozeb-induced apoptosis was accompanied by up-regulation of Bax and down-regulation of Bcl-2 and Bcl-xL. Overall, our data suggested that mancozeb caused ROS generation which induced significant (P < 0.05) apoptosis in AGS cells that was attenuated with pretreatment of NAC. More importantly, same concentration of mancozeb did not show any considerable effect on cell growth, death, cell cycle arrest and ROS generation in normal FHs 74 Int cells. Overall, for the first time these results suggest that mancozeb has selective anticancer activity at lower concentrations against gastric cancer cells.

Topics: Apoptosis; bcl-X Protein; Caspase 3; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cell Survival; Humans; Maneb; Membrane Potential, Mitochondrial; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Stomach Neoplasms; Up-Regulation; Zineb

Black sigatoka is the main disease of banana crop production and is controlled by using either systemic or contact fungicides through spray applications. Biological efficacy is typically assessed on a whole cropping cycle with a natural infestation and periodic spray applications. Developing a faster methodology for assessment of the biological efficacy of a contact fungicide offers promising perspectives for testing current and new fungicides or application techniques.. The methodology is based on the time of occurrence of the first BLSD symptoms. An artificial infestation protocol was optimized by multiplying the infestation spots and by covering the infested plants. Biological efficacy tests were based on a single spray application after infestation combining three mancozeb dose reductions and two nozzle types. Results demonstrated that a 50% reduction in the mancozeb rated dosage gave significant efficacy independently of the nozzle type, with a reduction of the number of lesions of up to 55% compared with control plants.. The described method provides rapid and significant infestation. Further comparison of spray settings and fungicide doses was possible. This methodology will be tested at the plantation scale over a longer period covering the whole crop cycle. © 2018 Society of Chemical Industry.

Topics: Drug Resistance, Fungal; Fungicides, Industrial; Maneb; Musa; Pest Control; Plant Diseases; Zineb

Advanced gold (Au) and silver (Ag) nanostructures were produced by laser techniques on printer paper substrate. Surface-enhanced Raman spectroscopy (SERS) analyses of the fungicide mancozeb (Dithane DG) and insecticide thiamethoxam (Aktara 25 BG) in quantities smaller than usually applied in agricultural medicine were performed for the first time assisted by the structures fabricated. The investigations and results show an easy alternative and cheap way to detect small amounts or residue of harmful environmental pollutants, which has a direct bearing on food quality and thus on human health.

Topics: Environmental Pollutants; Food Analysis; Fungicides, Industrial; Gold; Insecticides; Maneb; Metal Nanoparticles; Silver; Spectrum Analysis, Raman; Thiamethoxam; Zineb

Soil microorganisms exhibit varying levels of metal tolerance across a diverse range of environmental conditions. The use of metal-based fungicides such as mancozeb and copper oxychloride could potentially result in increased levels of manganese, zinc and copper which may adversely affect soil mesofauna. Under standardized earthworm bioassay conditions (temperature, pH, soil type and water content), we investigated the effect of Bacillus cereus on mancozeb and copper oxychloride ecotoxicity towards Eisenia andrei. A metal-tolerant Bacillus cereus strain previously isolated from a gold mining site was introduced into fungicide spiked soils. Earthworms were exposed to bacterial inoculated and non-inoculated substrates of mancozeb (8, 44, 800 and 1250 mg kg

Topics: Animals; Bacillus cereus; Copper; Environmental Monitoring; Fungicides, Industrial; Maneb; Oligochaeta; Soil; Soil Pollutants; Zineb

Mancozeb is a fungicide widely used in agriculture, mostly against the pathogen Glomerella cingulata responsible for the rot of ripe grape, but presents high toxicity. Strategies are sought to reduce the toxicity of this fungicide and alternative treatments are welcome. An alternative could be the use of clove oil, which has Eugenol as its major compound, and has antifungal potential against G. cingulata, however, Eugenol is susceptible to degradation processes which may compromise its efficacy. The nanoencapsulation of Mancozeb and Eugenol is a possible strategy to overcome the limitations of toxicity, solubility and instability of these compounds. Therefore, the objective of this study is to develop nanoemulsions containing Mancozeb (0.1 mg/mL) and Eugenol (33 mg/mL), isolated or associated, and evaluate the safety of these formulations through cytotoxicity, genotoxicity and ecotoxicity tests. Nanoemulsions were developed by the spontaneous emulsification method, cytotoxicity and genotoxicity were evaluated in healthy human cells through MTT, Dichlorofluorescein diacetate and Picogreen tests, and ecotoxicity assessment was carried out using the chronic toxicity test in springtails. After preparation, the physicochemical characterization of the nanoemulsions were performed which presented mean particle size between 200 and 300 nm, polydispersity index less than 0.3, negative zeta potential and acid pH. The nanoencapsulation was able to avoid the reduction of the cell viability caused by Mancozeb, while Eugenol was shown to be safe for cell use in both free and nanostructured forms, however the association of the two active compounds showed toxicity in the higher doses of Mancozeb. In the ecotoxicity tests, both free Mancozeb and Eugenol forms presented high toxic potential for soil, whereas the nanoencapsulation of these compounds did not cause a reduction in number of springtails. Therefore, from the tests performed, it was possible to observe that nanoencapsulation of Mancozeb and Eugenol is a safe alternative for the application of these compounds mainly in agriculture.

Topics: Animals; Arthropods; Cell Survival; DNA Damage; Drug Synergism; Emulsions; Eugenol; Fungicides, Industrial; Humans; Leukocytes, Mononuclear; Maneb; Nanocapsules; Particle Size; Phyllachorales; Soil; Toxicity Tests; Zineb

The aim of this study was to evaluate the role of apoptosis in the first-generation pups' testicular and ovarian tissue changes following mancozeb (MNZ) administration during intrauterine and lactating periods and also the preventive effect of the co-administration of vitamins E and C on these changes. Naval Medical Research Institute (NMRI) pregnant mice were randomly divided into six groups: control, vehicle, MNZ, vitamin E plus MNZ, vitamin C plus MNZ and vitamins E and C plus MNZ. Administered doses of MNZ and vitamins E and C were 500, 200 and 100 mg/kg of body weight, respectively. These agents were administered to the animals by oral gavage every 2 days. Vitamin treatment was carried out 30 min prior to MNZ administration. Treatment was started on the second day of gestation and continued until weaning. Separated testes and ovaries of animals were prepared for apoptosis detection by terminal deoxynucleotidyl transferase end-labeling (TUNEL) staining. The percentage of TUNEL-positive cells was reported using the 4,6-diamidino-2-phenylindole method. As compared to the control and vehicle groups, MNZ induced a significant increase ( p < 0.001) in the number of TUNEL-positive cells. The administration of both vitamins E and C alone and together significantly ( p < 0.001) prevented the apoptotic impacts of MNZ. The preventive effect of the co-administration of these vitamins on the ovary was greater compared to the single administration of vitamins E ( p < 0.001) or C ( p < 0.001). Meanwhile, the results revealed the stronger preventive effect of vitamin C as compared to E on testicular tissue ( p < 0.05). The apoptotic impact of MNZ exposure during intrauterine and lactating periods on first-generation testicular and ovarian tissues was significant. The co-administration of vitamins E and C could prevent MNZ-induced testicular and ovarian changes.

Topics: Animals; Animals, Newborn; Apoptosis; Ascorbic Acid; Environmental Exposure; Female; Male; Maneb; Mice; Ovary; Protective Agents; Testis; Vitamin E; Zineb

Absorbed dose assessment from dermal exposure involves multiplying skin contamination by the dermal absorption coefficient, which is usually defined for the standard workday of 8 h. This strategy may suffer from limitations when the duration of exposure is extremely variable, such as in agricultural exposure to pesticides.. The aim of this study was to estimate the dose of mancozeb absorbed by agricultural pesticide applicators in a typical working day considering the real duration of exposure, to compare these estimates with those coming from the use of the Fixed Fractional Approach, and to assess the suitability of the dose estimates in the interpretation of biological monitoring results.. In a series of real-life field studies on 29 workers applying mancozeb in vineyards for 38 work days, three sets of data were collected: information regarding work activities for each work day, potential (on clothes) and actual skin exposure using the "patch" methodology, and excretion of ethylenethiourea (ETU) in the 24-h pre-exposure and 24-h post-exposure urine samples. The statistical analyses were done using the R Language and Environment for Statistical Computing.. Accounting for the duration of exposure led to a substantial reduction in the absorbed dose estimates, compared to the estimates coming from the Fixed Fractional Approach. In particular, absorbed dose by the body, hands' and total absorbed dose were reduced by 50%, 81%, and 80% respectively. The body dose estimated considering both approaches still correlated better with post-exposure 24-h urine ETU levels than the hands' dose, although more than 90% of the estimated total absorbed dose comes from the hands.. An accurate estimate of the absorbed dose, carried out considering the real duration of exposure, can result in a higher correlation with a biomarker of occupational exposure, such as urine ETU, or at least yield more accurate results. This can facilitate the interpretation of biological monitoring data in pesticide-exposed agricultural workers despite the absence of biological exposure limits. ETU should be evaluated as a potentially relevant source of exposure due to ethylenebisdithiocarbamates' (EBDCs) degradation in the formulated product or spray mixture.

Topics: Ethylenethiourea; Farmers; Fungicides, Industrial; Humans; Male; Maneb; Models, Theoretical; Occupational Exposure; Personal Protective Equipment; Risk Assessment; Skin Absorption; Zineb

The present study was designed to evaluate genotoxic markers of mancozeb exposure and withdrawal in colon and liver tissues together with histological changes in the gastrointestinal tract of Sprague Dawley rats. Thirty rats were divided into three equal groups; group I: treatment, 250 mg/kg mancozeb dissolved in corn oil administered twice weekly for 7 weeks; group II: withdrawal, the same treatment as group I after which animals were untreated for 5 weeks; group III: control, administered corn oil on the same schedule as group I for 7 weeks. All administrations were by oral gavage. Serum samples were analyzed for biochemical parameters. The comet assay and histopathological examinations were done on liver and colon specimens. The results demonstrated that mancozeb exposure caused significant increases in triglycerides and total cholesterol accompanied by decreases in glucose levels, with extensive DNA damage in liver and colon together with pathological changes in stomach, colon, and liver. Mancozeb withdrawal for 5 weeks improved the lipid and glucose profiles and decreased the degree of DNA damage and changes in the architecture of the stomach, colon, and liver. We concluded that discontinuing exposure to mancozeb fungicide for 5 weeks could ameliorate the adverse effects induced by 7 weeks of exposure to mancozeb. A longer withdrawal time may further reduce the observed genotoxicity.

Topics: Animals; Blood Glucose; Colon; Comet Assay; DNA Damage; Fungicides, Industrial; Lipids; Liver; Male; Maneb; Mutagenicity Tests; Organ Size; Rats; Rats, Sprague-Dawley; Stomach; Zineb

The study aims to evaluate the potential reproductive toxicity induced by mancozeb fungicide in male rabbits and to examine the ameliorative effect of glutathione (GSH), a non-enzymatic antioxidant, against mancozeb reproductive toxicity. Mancozeb is a member of the dithiocarbamates group currently in use in the management of fungal diseases of plants. To achieve these aims, mature male White New-Zealand rabbits of 4-5 months old were randomly assigned to four groups of 9 animals each: control, mancozeb only, mancozeb and GSH, and GSH only. This study discovered a significant reduction in serum FSH, LH, testosterone and testicular LDH, ACP, and ALP levels in the groups of mancozeb-treated rabbits compared with control. The mancozeb-treated groups also showed significant losses in sperm viability, along with a significant increase in the number of abnormal sperms. Finally, an upregulation in steroidogenic 3β-HSD enzyme activity was noted in mancozeb-treated rabbits. Histopathological inspection of the testicles established disruption of the germinal epithelium with vacuolization of Leydig cells and reduced spermatogenic cells. GSH co-administration increased serum concentrations of FSH, LH, testosterone, and levels of the testicular enzymes: LDH, ACP, and ALP. Improved steroidogenesis was indicated in this group by a significant improvement in the testicular 3β-HSD enzyme, by a significant increase in sperm viability, and by a significant decrease in the number of abnormal sperms. The findings of this study suggest that mancozeb exposure has anti-spermatogenic and anti-steroidogenic adverse effects in rabbits and administration of GSH may alleviate the reproductive toxicity.

Topics: Animals; Antioxidants; Fertility; Follicle Stimulating Hormone; Fungicides, Industrial; Glutathione; Luteinizing Hormone; Male; Maneb; Rabbits; Random Allocation; Reproduction; Spermatogenesis; Spermatozoa; Testis; Testosterone; Zineb

Lead and mancozeb are two important chemicals used for different human purposes and activities worldwide. Hazard assessment in different areas of the world is carried out with different but phylogenetically similar species, adapted to different climatic conditions, in order to increase relevance. This study evaluated the sensitivity of two monophyletic species, the tropical species Daphnia similis and the temperate species Daphnia magna, to the two chemicals lead and mancozeb. Standard acute and chronic ecotoxicological tests (reproduction and growth), as well as other sublethal measurements such as the intrinsic rate of population increase (r), feeding rate (FR) and O

Topics: Animals; Biological Assay; Daphnia; Ecotoxicology; Lead; Maneb; Phylogeny; Reproduction; Species Specificity; Toxicity Tests; Water Pollutants, Chemical; Zineb

Mancozeb is a dithiocarbamate non-systemic fungicide widely used to control fungal diseases of plants, commonly applied in apple orchards in Brazil. Instead of its common use, there are no reports about the risk to non-target organisms in Brazilian soils. We studied the risk of Mancozeb (in the commercial formulation Dithane

Topics: Animals; Arthropods; Brazil; Fungicides, Industrial; Invertebrates; Maneb; Oligochaeta; Plants; Reproduction; Soil; Soil Pollutants; Toxicity Tests; Zineb

Early caregiving is one of the strongest influences on children's development, and among the most significant modifiable environmental factor. The aim of this study was to explore the association between quality of caregiver-infant interactions and neurodevelopment of infants living in banana-growing communities in rural Costa Rica characterized as having environmental toxic exposures. Home visits were conducted with 94 caregiver-infant dyads from the Infants' Environmental Health Study (ISA), living within Matina county, Limón province. One-year infant neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development®, Third Edition (Bayley-III). Quality of caregiver-infant interaction was assessed with a standardized observational task: Nursing Child Assessment Satellite Training Teaching scale (NCATS) at around two years of age. Multiple regression analyses examined associations between components of caregiver-infant interactions and neurodevelopmental outcomes, adjusting for mancozeb and manganese exposure and other potential confounders. Compared to NCATS normative data for U.S. Hispanic mothers, 35% of the sample had overall caregiving interaction scores ≤10th percentile cut-off, indicating less than optimal interactions. Higher quality of caregiver-infant interaction was associated with higher expressive communication ability in infants [ß = 0.03 (95% CI: 0.01, 0.06)], controlling for pesticide exposure and confounders. Aspects of caregiving such as stimulation and growth-fostering of infants were most strongly associated with language outcomes. Results suggest an association between positive caregiving on language development for infants living in a rural agricultural area in Costa Rica, and highlight aspects of caregiving that could be targeted to improve resilience of these children who live in vulnerable conditions.

Topics: Adult; Child Development; Child, Preschool; Costa Rica; Environment; Environmental Exposure; Environmental Health; Female; Fungicides, Industrial; Humans; Infant; Infant Care; Infant, Newborn; Language Development; Male; Maneb; Manganese Poisoning; Mothers; Neuropsychological Tests; Pesticides; Resilience, Psychological; Rural Population; Zineb

Mancozeb (MZ), chlorothalonil (CT), and thiophanate methyl (TM) are pesticides commonly used in agriculture due to their efficacy, low acute toxicity to mammals, and short environmental persistence. Although the toxic effects of these pesticides have been previously reported, studies regarding their influence on the immune system are limited. As such, this study focused on the immunomodulatory effect of MZ, CT, and TM pesticides on macrophage cells. RAW 264.7 cells were exposed to a range of concentrations (0.1-100 μg/mL) of these pesticides. CT exposure promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) levels. The MTT and ds-DNA assay results demonstrated that MZ, CT, and TM exposure induced macrophage proliferation. Moreover, MZ, CT, and TM promoted cell cycle arrest at S phase, strongly suggesting macrophage proliferation. The levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) and caspases (caspase 1, 3, and 8) in macrophages exposed to MZ, CT, and TM pesticides increased, whereas the anti-inflammatory cytokine levels decreased. These results suggest that MZ, CT, and TM exert an immunomodulatory effect on the immune system, inducing macrophage activation and enhancing the inflammatory response.

Topics: Animals; Cytokines; Immunomodulation; Interleukin-1beta; Macrophages; Maneb; Nitric Oxide; Nitriles; Pesticides; Reactive Oxygen Species; Thiophanate; Toxicity Tests; Tumor Necrosis Factor-alpha; Zineb

Mancozeb (MZ) is a widely used ethylene-bis-dithiocarbamate fungicide in agriculture causing hepatoxic and genotoxic effects in rats. Curcumin (CUR) has various pharmacological effects including antioxidant and anti-inflammatory properties. This study investigated the efficacy of CUR in mitigating MZ-induced hepatotoxicity and genotoxicity in rats. Twenty-four male rats were divided into four equal groups; group I (control) was given carboxymethyl cellulose, group II was orally administered CUR (100 mg/kg b.wt), group III was gavaged with MZ (750 mg/kg b.wt), and group IV was co-treated with MZ and CUR at the same doses daily for 10 weeks. As a result, the concurrent treatment with CUR and MZ minimized the increased levels of liver function markers in serum, lipid peroxidation, pro-inflammatory mediators and DNA damage parameters in liver. In addition, CUR administration improved the depleted markers of hepatic antioxidant status in MZ-treated rats. Moreover, CUR protected the liver against the histological alterations elicited by MZ exposure and also, reduced the immunopositive reactivity of pro-apoptotic p53 in cytoplasm of hepatocytes. The present findings suggest that CUR exerts a significant protective effect against MZ-induced hepatotoxicity and genotoxicity.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury; Curcumin; DNA Damage; Hepatocytes; Lipid Peroxidation; Male; Maneb; Oxidative Stress; Rats; Zineb

Grapevine is a vulnerable crop to several fungal diseases often requiring the use of ethylenebisdithiocarbamate (EBDC) fungicides, such as mancozeb. This fungicide has been reported to have goitrogenic, endocrine disrupting, and possibly immunotoxic effects. The aim of this study was to assess workers' exposure in two scenarios of mancozeb application and analyse the main determinants of exposure in order to better understand their mechanism of influence. Environmental monitoring was performed using a modified Organisation for Economic Co-operation and Development (OECD) "patch" methodology and by hand-wash collection, while mancozeb's metabolite, ethylenethiourea (ETU), was measured in 24-h preexposure and postexposure urine samples. Liquid chromatography-mass spectrometry was used for determination of mancozeb and ETU in different kinds of samples. Closed tractor use resulted in 40 times lower potential exposure compared with open tractor. Coveralls reduced skin exposure 4 and 10 times in case of open and closed tractors, respectively. Gloves used during application resulted in 10 times lower hand exposure in open but increased exposure in closed tractors. This study has demonstrated that exposure to mancozeb is low if safe occupational hygiene procedures are adopted. ETU is confirmed as suitable biological marker of occupational exposure to mancozeb, but the absence of biological exposure limits significantly reduces the possibility to interpret biological monitoring results in occupationally exposed workers.

Topics: Adult; Agriculture; Biomarkers; Environmental Monitoring; Ethylenethiourea; Farms; Fungicides, Industrial; Gloves, Protective; Humans; Italy; Male; Maneb; Middle Aged; Occupational Exposure; Protective Clothing; Risk Assessment; Surveys and Questionnaires; Zineb

Nigella sativa oil (NSO) possesses antioxidant activity. However, its protective role against the hazards of fungicides has been poorly studied. Therefore, the present work aimed at determining the ameliorative potential of NSO against hepatotoxicity induced by carbendazim (CBZ) and/or mancozeb (MNZ) in female rats. In the present study, about 120 adult female Sprague-Dawley rats were randomly divided into eight equal groups. One group of animals was kept as a negative control (Gp. 1); groups 2, 3 and 4 orally received CBZ (200 mg/kg body wt) and/or MNZ (300 mg/kg body wt) daily for 2 weeks (positive groups). In order to assess the hepatoprotective potential of NSO, in comparison with NSO-treated rats (Gp. 5), groups 6, 7 and 8 were CBZ- and/or MNZ-exposed groups pre-treated orally with NSO (2 ml/kg body wt) daily for 2 weeks (prophylactic groups). All groups were kept further for 15 days without medications to observe the withdrawal effect. At the end of exposure and withdrawal periods, the body weight of all experimental rats was recorded and blood samples were collected for hematological, clinico-biochemical, and micronucleus assays. The animals were then sacrificed, and the liver and bone marrow were harvested for oxidative stress bioassay, chromosomal aberrations, DNA fragmentation, and histopathological examinations. The results suggested that pre-treatment with NSO remarkably diminished CBZ- and MNZ-induced macrocytic hypochromic anemia, leukocytosis, lymphocytosis, eosinophilia, and neutropenia. Besides, it also minimized the elevated liver enzymes, lipid peroxidation, micronucleus incidence, DNA damage, and chromosomal aberration frequency. Conversely, NSO significantly stimulated the CBZ- and/or MNZ-induced antioxidant system suppression. The NSO also normalized the hepatic structural architecture. As far as withdrawal effect is concerned, there was almost disappearance of the bad effects of these fungicides and the values were close to the normal range especially with the use of NSO. Ultimately, the results revealed that N. sativa oil is an effective hepatoprotective agent due to its genoprotective and free radical scavenging activities.

Topics: Animals; Antioxidants; Benzimidazoles; Carbamates; Chromosome Aberrations; DNA Fragmentation; Female; Fungicides, Industrial; Liver; Maneb; Micronuclei, Chromosome-Defective; Plant Oils; Protective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Zineb

Mancozeb, an ethylene bis-dithiocarbamate, is widely used as a fungicide and exerts reproductive toxicity in vivo and in vitro in mouse oocytes by altering spindle morphology and impairing the ability to fertilize. Mancozeb also induces a premalignant status in mouse granulosa cells (GCs) cultured in vitro, as indicated by decreased p53 expression and tenuous oxidative stress. However, the presence and extent of ultrastructural alterations induced by mancozeb on GCs in vitro have not yet been reported. Using an in vitro model of reproductive toxicity, comprising parietal GCs from mouse antral follicles cultured with increasing concentrations of mancozeb (0.001-1 µg/ml), we sought to ascertain the in vitro ultrastructural cell toxicity by means of transmission (TEM) and scanning (SEM) electron microscopy. The results showed a dose-dependent toxicity of mancozeb on mouse GCs. Ultrastructural data showed intercellular contact alterations, nuclear membrane irregularities, and chromatin marginalization at lower concentrations, and showed chromatin condensation, membrane blebbing, and cytoplasmic vacuolization at higher concentrations. Morphometric analysis evidenced a reduction of mitochondrial length in GCs exposed to mancozeb 0.01-1 µg/ml and a dose-dependent increase of vacuole dimension. In conclusion, mancozeb induced dose-dependent toxicity against GCs in vitro, including ultrastructural signs of cell degeneration compatible with apoptosis, likely due to the toxic breakdown product ethylenethiourea. These alterations may represent a major cause of reduced/delayed/missed oocyte maturation in cases of infertility associated with exposure to pesticides.

Topics: Animals; Apoptosis; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Granulosa Cells; Maneb; Mice; Oxidative Stress; Zineb

The present experiment was designed to monitor the morphotoxic, cytotoxic and genotoxic potential of Mancozeb (fungicide) in non-target plants using bulbs of Allium cepa. Mancozeb is classified as a contact fungicide and is registered for use on a variety of crop plants. In the present monitoring, Allium cepa bulbs were exposed to different concentrations of mancozeb viz., 10, 30, 50, 70, 90, 110, 130 and 150 ppm for 24 and 48 h. The potential morphotoxic and cytotoxic effects of mancozeb were examined by determining the average root number, average root length, mitotic index, relative abnormality rate (%) and frequency of abnormalities (%). A progressive significant concentration and time dependent inhibition of the average root number, average root length indicated the morphotoxic nature. The cytotoxic effect was significantly increased for 48 h treatment as compared to 24 h treatment time, by reducing the mitotic index of meristematic cells. The results indicated an indirect genotoxic effect by inducing different types of chromosomal abnormalities, likely sticky, disoriented and fragmented chromosomes. Thus indicating that the investigated fungicide have genotoxic potential due to abnormal DNA condensation and chromosome coiling by spindle inactivation. The observations of cyto and genotoxic effects suggest that the fungicide mancozeb is clastogenic agent. Thus the different concentrations used in the field could be harmful for the end-receptors of food-chain and needs constant monitoring and management for the better development of crop plants.

Topics: Biological Assay; Chromosome Aberrations; DNA Damage; Fungicides, Industrial; Maneb; Meristem; Mutagens; Onions; Plant Roots; Zineb

In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb-induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo-osmotic swelling-tail swelled sperm was observed in mancozeb-treated rats. The activity levels of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase and circulatory testosterone levels were significantly decreased in mancozeb-treated rats. Exposure to mancozeb resulted in a significant decrease in glutathione levels and superoxide dismutase and catalase activity levels with an increase in lipid peroxidation levels in the testes and epididymis. Coadministration of forskolin mitigated the mancozeb-induced oxidative toxicity and suppressed steroidogenesis and spermatogenesis.

Topics: 17-Hydroxysteroid Dehydrogenases; Animals; Antioxidants; Colforsin; Epididymis; Fungicides, Industrial; Glutathione; Lipid Peroxidation; Male; Maneb; Oligospermia; Organ Size; Oxidative Stress; Progesterone Reductase; Random Allocation; Rats, Wistar; Sperm Motility; Spermatogenesis; Testis; Testosterone; Zineb

The exposure to pesticides by nontarget soil biota has long been regarded as a serious downside of modern agricultural regimes and the subject of heated debate. Of utmost relevance is the exposure to pesticide mixtures because their effects have been shown to not necessarily reflect the individual toxicity of their components, and even the simple addition of effects may lead to consequences not clearly anticipated. In the present study, a multiple biomarker approach was employed to identify the mechanistic and time effects underlying several single and mixture treatments of chlorpyrifos (CPF) and mancozeb (MCZ) in juveniles and adults of the terrestrial isopod Porcellionides pruinosus. The effects of the individual pesticides and the mixtures at recommended doses were mostly transitory under these controlled conditions and one-pulse exposure. Whereas imbalances were identified on detoxification and oxidative stress-related enzymes, the isopods generally showed the ability to recover through the end of the experiment. However, juveniles displayed greater vulnerability than adults. Most of the differences between life stages occurred in energy-related parameters where distinct performances and stress-handling behaviors were observed, suggesting higher metabolic costs to juveniles. Our results stress that understanding the time dependence of the underlying mechanisms governing the joint effects of the pesticides can help in assessing and anticipating the effects of the pesticide mixtures. Moreover, we emphasize the importance of taking life stage-related differences into consideration when evaluating the environmental risks of pesticides and pesticide mixtures. Environ Toxicol Chem 2018;37:1446-1457. © 2018 SETAC.

Topics: Acetylcholinesterase; Animals; Biomarkers; Catalase; Chlorpyrifos; Energy Metabolism; Glutathione Transferase; Inactivation, Metabolic; Isopoda; Life Cycle Stages; Maneb; Oxidative Stress; Pesticides; Zineb

Topics: Alanine; Animals; Cattle; Cells, Cultured; Female; Fungicides, Industrial; Luteal Cells; Maneb; Progesterone; Triazoles; Zineb

Manganese (Mn)-containing dithiocarbamates such as Mancozeb (MZ) have been shown to induce oxidative stress-related toxicity in rodents and humans. However, little is known about the neurotoxic effects induced by MZ in fish. In this study, carp (Cyprinus carpio) were exposed to non-lethal waterborne concentrations of MZ, and oxidative stress parameters as well as metal accumulation in fish brains were evaluated. The experimental groups were as follows: control, MZ 5 mg/L, and MZ 10 mg/L. Fish were exposed for 7 days, and then brain was removed and prepared for subsequent analysis of antioxidant enzymes, reactive oxygen species (ROS), and expression of Nrf2 and phosphoNrf2. In parallel, manganese (Mn) levels were evaluated in blood and brain tissues. Mn levels were significantly increased in blood and brain of MZ-exposed carps. In addition, a concentration-dependent increase (p < 0.05) in ROS levels was observed in parallel to increments (p < 0.05) in the activity of major antioxidant enzymes, such as GPx, GR, and GST. On the other hand, significant decreases (p < 0.05) in CAT and SOD activities were observed. The expression of total and phosphorylated forms of Nrf2 was significantly (p < 0.05) upregulated in the brain of carps exposed to Mz when compared to the control, indicating an activation of the Nrf2 antioxidant pathway. Our study showed for the first time the activation of the Nrf2/ARE pathway and bioaccumulation of Mn induced by MZ exposure in fish species, highlighting important mechanisms of action and its toxicological impacts to aquatic organisms.

Topics: Animals; Antioxidants; Brain; Carps; Dose-Response Relationship, Drug; Fish Proteins; Fungicides, Industrial; Maneb; Manganese; NF-E2-Related Factor 2; Water Pollutants, Chemical; Zineb

Food intake ensures energy resources sufficient for basic metabolism, immune system and reproductive investment. It is already known that food-seeking performances, which are crucially controlled by orexins (ORXs), may be under the influence of environmental factors including pollutants. Among these, mancozeb (mz) is becoming an environmental risk for neurodegenerative diseases. Due to few studies on marine fish exposed to mz, it was our intention to correlate feeding latency, food intake and feeding duration to potential neurodegenerative processes in key diencephalic sites and expression changes of the ORX neuroreceptor (ORXR) in the ornate wrasses (Thalassoma pavo). Hence, fish exposed for 4 days (d) to mz 0.2 mg/l (deriving from a 0.07, 0.14, 0.2, 0.3 mg/l screening test) displayed a significant reduction (p < 0.05) of food intake compared to controls as early as 1d that became more evident (p < 0.01) after 3d. Moreover, significant enhancements of feeding latency were reported after 1d up to 3d (p < 0.001) and even feeding duration was enhanced up to 3d (p < 0.001), which instead moderately increased after 4d (p < 0.05). A reduction (-120%; p < 0.001) of mean body weight was also detected at the end of exposure. Likewise, a notable (p < 0.001) activation of ORXR protein occurred together with mRNA up-regulations in diencephalic areas such as the diffuse nucleus of the inferior lobe (+48%) that also exhibited evident degenerative neuronal fields. Overall, these results highlight an ORX role as a vital component of the neuroprotective program under environmental conditions that interfere with feeding behaviors.

Topics: Animals; Feeding Behavior; Female; Fishes; Fungicides, Industrial; Gene Expression; Maneb; Neurodegenerative Diseases; Orexin Receptors; Paraventricular Hypothalamic Nucleus; Zineb

This study determined the function of thioredoxin and glutaredoxin systems in the phytopathogenic fungus

Topics: Alternaria; Antifungal Agents; Biphenyl Compounds; Citrus; Drug Resistance, Fungal; Gene Deletion; Gene Expression Regulation, Fungal; Glutaredoxins; Glutathione Reductase; Hydrogen Peroxide; Maneb; NADPH Oxidases; Niacinamide; Nitriles; Oxidative Stress; Peroxiredoxins; Plant Leaves; Reactive Oxygen Species; Sulfhydryl Compounds; Thioredoxin-Disulfide Reductase; Thioredoxins; Zineb

Arbuscular mycorrhizal fungi (AMF) are mutualistic symbionts considered a key group in soil systems involved in the provision of several ecosystem services. Recently they have been listed by EFSA as organisms to be included in the test battery for the risk assessment of plant protection product (PPPs). This study aimed to contribute to improve the ISO Protocol (ISO 10832: 2009) by assessing the feasibility of using other AMF species under different test conditions. Overall, results showed that AMF species Gigaspora albida and Rhizophagus clarus (selected out of five AMF species) are suitable to be used in spore germination tests using the ISO protocol (14 days incubation with sand or artificial soil as substrate) to test PPPs. However, several modifications to the protocol were made in order to accommodate the use of the tested isolates, namely the incubation temperature (28 °C instead of 24 °C) and the change of reference substance (boric acid instead of cadmium nitrate). The need for these changes, plus the results obtained with the three fungicides tested (chlorothalonil, mancozeb and metalaxyl-M) and comparisons made with literature on the relevance of the origin of AMF isolates in dictating the adequate test conditions, emphasize the importance of adjusting test conditions (AMF species/isolates and test temperature) when assessing effects for prospective risk assessment targeting different climatic zones. So, further studies should be conducted with different AMF species and isolates from different climatic regions, in order to better define which species/isolate and test conditions should be used to assess effects of a particular PPP targeting a given climatic zone.

Topics: Alanine; Fungicides, Industrial; Glomeromycota; Maneb; Mycorrhizae; Nitriles; Risk Assessment; Soil; Soil Microbiology; Temperature; Time Factors; Toxicity Tests; Zineb

Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited.. We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica.. We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1-3 times during pregnancy from mothers enrolled in the Infants' Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure-outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment.. Median (P25-P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3 μg/L (2.4-4.9; specific gravity-corrected), 1.7 μg/g (0.9-4.1), and 24.0 μg/L (20.3-28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [β per 10-fold increase=-7.4 points (95% CI: -15.2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [-3.0 (-6.1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [-4.6 (-8.5, -0.8)]. We observed null associations for blood Mn, language, and motor outcomes.. Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955.

Topics: Environmental Exposure; Environmental Health; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Infant; Male; Maneb; Manganese; Maternal Exposure; Neurodevelopmental Disorders; Pregnancy; Zineb

Mancozeb (MZB) is one of the fungicides used in pest control programs that might affect human health including reproductive system. The aim of this study was to demonstrate the mechanisms through which MZB induces testicular tissue damage and the probable protective effect of N-acetylcysteine (NAC), a modified amino acid, with antioxidant property, against MZB toxicity in an animal model. Male albino mice ( n = 8) were exposed to different doses of MZB (250 and 500 mg/kg/day) by oral gavage without or with NAC (200 mg/kg, twice/week) for 40 days. Sub-chronic MZB dose-dependently decreased sperm motility and count. Exposure to MZB increased lipid peroxidation and protein carbonyl, while it reduced antioxidant enzymes activities, total antioxidant capacity, and glutathione content. The histopathological examination clearly showed deleterious changes in the testicular structure. At the molecular levels, the results of quantitative real time-poly chain reaction (qRT-PCR) showed that MZB upregulated oxidative stress markers inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX4) and downregulated expression of the glutathione peroxidase 1 (Gpx1) gene as one of the most important antioxidant enzymes. MZB also induced apoptosis dose-dependently in the testes as determined by the terminal dUTP nick-end labeling assay and immunoblotting. NAC administration decreased the mRNA levels of both iNOS and NOX4 with a concomitant increase in Gpx1 expression. It also significantly decreased MZB-induced oxidative stress and apoptosis. Collectively, the present study showed MZB-induced oxidative damage in testes leading to apoptosis. It revealed that antioxidants such as NAC can mitigate oxidant injury induced by the dithiocarbamate pesticides in the reproductive system.

Topics: Acetylcysteine; Animals; Antioxidants; Apoptosis; Male; Maneb; Mice; Oxidative Stress; Spermatogenesis; Testis; Zineb

The 1,2,3-triazole ring fused with pyridine/pyrimidine was explored as new template for the identification of potential antimicrobial agents. The regioselective synthesis of these pre-designed N-heteroarenes was achieved via exploring the application of Buchwald's strategy (i.e. C-N bond formation/reduction/diazotization/cyclization sequence) to the N-heteroarene system. Two of them showed promising antibacterial (comparable to streptomycin) and several showed potent antifungal (comparable to mancozeb) activities.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacillus subtilis; Cyclization; Drug Design; Escherichia coli; Fusarium; Maneb; Microbial Sensitivity Tests; Molecular Structure; Oxidation-Reduction; Pyridines; Pyrimidines; Streptomycin; Triazoles; Zineb

Mancozeb, a dithiocarbamate widely used in agriculture, is considered a developmental hazard in humans; however, more evidences are still needed concerning the consequences of chronic exposure to this pesticide. Mancozeb neurotoxicity in developing mouse hypothalamus was evaluated by subchronic exposure of male Mus musculus mice to low and high doses of mancozeb (30 and 90 mg/kg body weight, respectively) from late neonatal until adolescence. Variations in hypothalamic amino acid neurotransmitter levels and changes in histological as well as cytological characteristics were analyzed in young adult experimental mice and compared with control. A dose-dependent increase in excitation/ inhibition ratio was observed in mancozeb-exposed hypothalamus, indicating an overall state of excitoxicity. Histopathological and ultrastructural studies showed increased apoptosis, neuroinflammation and demyelination, demonstrating mancozeb-induced cytotoxicity in hypothalamic neurosecretory cells. In summary, both neurochemical and morphological data revealed mancozeb-induced alterations during development of hypothalamic circuitry that are critical for maturation of the neuroendocrine system.

Topics: Animals; Fungicides, Industrial; Hypothalamus; Male; Maneb; Mice; Microscopy, Electron, Transmission; Neurotransmitter Agents; Zineb

The pesticide mancozeb (mz) is recognized as a potent inducer of oxidative stress due to its ability to catalyze the production of reactive oxygen species plus inhibiting mitochondrial respiration thus becoming an environmental risk for neurodegenerative diseases. Despite numerous toxicological studies on mz have been directed to mammals, attention on marine fish is still lacking. Thus, it was our intention to evaluate neurobehavioral activities of ornate wrasses (Thalassoma pavo) exposed to 0.2mg/l of mz after a preliminary screening test (0.07-0.3mg/l). Treated fish exhibited an evident (p<0.001) latency to reach T-maze arms (>1000%) while exploratory attitudes (total arm entries) diminished (-50%; p<0.05) versus controls during spontaneous exploration tests. Moreover, they showed evident enhancements (+111%) of immobility in the cylinder test. Contextually, strong (-88%; p<0.01) reductions of permanence in light zone of the Light/Dark apparatus along with diminished crossings (-65%) were also detected. Conversely, wrasses displayed evident enhancements (160%) of risk assessment consisting of fast entries in the dark side of this apparatus. From a molecular point of view, a notable activation (p<0.005) of the brain transcription factor pCREB occurred during mz-exposure. Similarly, in situ hybridization supplied increased HSP90 mRNAs in most brain areas such as the lateral part of the dorsal telencephalon (Dl; +68%) and valvula of the cerebellum (VCe; +35%) that also revealed evident argyrophilic signals. Overall, these first indications suggest a possible protective role of the early biomarkers pCREB and HSP90 against fish toxicity.

Topics: Animals; Behavior, Animal; Brain; Cyclic AMP Response Element-Binding Protein; Exploratory Behavior; Female; Fish Proteins; Fishes; Fungicides, Industrial; HSP90 Heat-Shock Proteins; Maneb; Motor Activity; Nerve Degeneration; Neurotoxicity Syndromes; Reaction Time; Time Factors; Water Pollutants, Chemical; Zineb

The effect of two thyroid disrupting pesticides (TDPs) mancozeb (MCZ) and imidacloprid (IMI) on the hypothalamic-pituitary-gonadal/testicular (HPG) axis of a seasonally breeding bird, Amandava amandava has been evaluated. Male birds (n=8/group) were exposed to each of the pesticide (0.25% LD

Topics: Animals; Endocrine Disruptors; Estradiol; Hypothalamus; Male; Maneb; Neonicotinoids; Nitro Compounds; Passeriformes; Peptide Hormones; Pesticides; Pituitary Gland; Testis; Testosterone; Thyroid Gland; Zineb

Topics: Chromatography, Liquid; Fruit; Fungicides, Industrial; Limit of Detection; Maneb; Reference Standards; Reproducibility of Results; Tandem Mass Spectrometry; Zineb

The increasing use of pesticides such as malathion and dithane in agriculture causes environmental mutagenicity. However, their genotoxicity in edible crops is seldom assessed. In this study, the genotoxic potential of malathion and dithane was evaluated in the roots of Vicia faba L. All three concentrations (0.05, 0.1, and 0.2%) of malathion and dithane tested resulted in a significant decrease in root length and inhibited seed germination. Cytological observations showed that the mitotic frequency in the root meristematic cells decreased parallel to the increase in concentrations, and the increase in chromosome aberrations and micronuclei frequency was concentration dependent. Alkaline comet assay revealed significant onset of DNA damage at all tested concentrations. For the randomly amplified polymorphic (RAPD)-polymerase chain reaction (PCR) analyses, 10 random RAPD primers were found to produce 116 unique polymorphic RAPD band fragments of 223-3139 bp. Each primer generated 3-15 RAPD bands on an average. The percentage of polymorphic DNA fragments was higher in malathion-exposed plants than dithane ones. The changes in RAPD profiles included disappearance and/or appearance of DNA bands in malathion and dithane treatment. Hence, DNA damage observed by the cytogenetic endpoints and comet assay corroborated with RAPD-PCR analysis. A total of 15 new protein bands of molecular weight ranging 11.894-226.669 kDa were observed in roots of Vicia plants that were exposed to the pesticides. The number of new protein bands was higher in malathion-treated DNA samples than in dithane-treated ones. Based on the results, we conclude that the pesticides can alter genomic template stability and change protein profiles. Malathion was more genotoxic than dithane. Therefore, RAPD assays can be useful in determining genotoxicity of pesticides in V. faba and other crops along with other quantitative parameters.

Topics: Chromosome Aberrations; Comet Assay; Crops, Agricultural; DNA Damage; Fungicides, Industrial; Gene Expression Profiling; Gene Expression Regulation, Plant; Genomic Instability; Germination; Insecticides; Malathion; Maneb; Micronuclei, Chromosome-Defective; Micronucleus Tests; Mutagenicity Tests; Mutagens; Osmolar Concentration; Plant Proteins; Plant Roots; Random Amplified Polymorphic DNA Technique; Seeds; Vicia faba; Zineb

Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

Topics: Animals; Antioxidants; Apoptosis; Cells, Cultured; Cytoprotection; Epigenesis, Genetic; Female; Fertility; Fungicides, Industrial; Gene Expression Regulation, Developmental; Maneb; Mice, Inbred ICR; Oocytes; Ovarian Follicle; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Stilbenes; Zineb

Italy is still characterized by a mild iodine deficiency and is among the most intensive users of chemical products for agriculture in Europe. The aim of this study was i) to evaluate thyroid effects of exposure to mancozeb, a fungicide widely used in agriculture, in a sample of Italian grapevine workers, and ii) to verify whether the iodine intake may modulate the risk of thyroid disruption due to the mancozeb metabolite ethylenthiourea (ETU).. One hundred seventy-seven occupationally exposed male workers (29 from Chianti, a mild iodine deficient area, and 148 from Bolzano an iodine sufficient province) and 74 non-occupationally exposed male controls (34 from Chianti and 40 from Bolzano) were enrolled in the study. Serum biomarkers of thyroid function, as well as urinary iodine and ETU concentrations were assessed. Moreover all the recruited subjects underwent clinical examination and thyroid ultrasound.. Multivariate comparisons showed lower mean serum levels of FT4 in Chianti-workers as compared to Bolzano-workers. Moreover, an increased urinary iodine excretion (>250µg/L) was more frequently found among more exposed workers (ETU>20µg/L) than among less exposed ones and this effect was more pronounced in Chianti- than in Bolzano-workers. Chianti-workers also showed a significantly higher frequency of very low thyroid volume (≤6.0ml) as compared to controls.. These findings showed a mild thyroid disrupting effect due to occupational exposure to mancozeb, more pronounced in workers residing in an area characterized by a mild to moderate iodine deficiency as compared to workers residing in an area covered by a long-lasting iodine prophylaxis program.

Topics: Adult; Aged; Agricultural Workers' Diseases; Case-Control Studies; Ethylenethiourea; Farmers; Fungicides, Industrial; Humans; Iodine; Italy; Male; Maneb; Middle Aged; Nutritional Status; Occupational Exposure; Thyroid Diseases; Thyroid Function Tests; Zineb

Mancozeb is a dithiocarbamate non-systemic agricultural fungicide with multi-site, protective action. It helps to control many fungal diseases in a wide range of field crops, fruits, nuts, vegetables, and ornamental plants. We have investigated the stability profiles of mancozeb in aqueous solutions to determine the effect of pH, temperature and light on the degradation process of mancozeb. In addition, the toxicological risk for humans associated with the joint intake of mancoze7b and its final degradation product, ethylenethiourea (ETU), was calculated and modelled as a function of the experimental conditions. Stability study results showed a very low stability profile of mancozeb in all the aqueous solutions with rapid degradation that varied with experimental conditions. The process followed first order kinetics. The study of the degradation kinetics showed a significant effect of pH*temperature interaction on the degradation process. The results also expressed that light has a greater impact on the stability of mancozeb and the formation of ETU. The current study concludes that mancozeb is unstable in aqueous solutions, particularly at an acid pH, in addition to presenting both severe light and lower temperature sensitivity. The toxicological risk associated with mancozeb degradation increases with time and temperature, being higher at basic pH and in absence of light.

Topics: Ethylenethiourea; Fungicides, Industrial; Half-Life; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Light; Maneb; Photolysis; Temperature; Time Factors; Water; Zineb

Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In this study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29, and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various end-points studied. Brain weight was significantly decreased in the mixture-exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture-exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture-exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture-exposed group offspring. Testosterone level was significantly decreased only at PND 29, but corticosterone level was increased at both PND 29 and PND 63 in mixture-exposed offspring. T-maze task performance revealed significantly increased time duration and reduced path efficiency in mixture-exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization.

Topics: Animals; Animals, Newborn; Brain; Endocrine Disruptors; Female; Hippocampus; Lactation; Male; Maneb; Maternal Exposure; Maze Learning; Memory, Short-Term; Mice; Neonicotinoids; Nitro Compounds; Pesticides; Pregnancy; Prenatal Exposure Delayed Effects; Pyramidal Cells; Testosterone; Zineb

Non-target organisms, including human and wildlife, are susceptible to deleterious effects of pesticide mixtures in their environment. Present study demonstrated the disruption of the hypothalamic-pituitary-thyroid (HPT) axis in a seasonally breeding wildlife bird Amandava amandava on co-exposure to dithiocarbamate mancozeb/MCZ and neonicotinoid imidacloprid/IMI, at concentrations even lower than respective environmentally realistic exposure level of each of the pesticide. Adult male birds (n=8/group) were exposed individually to 0.25% LD

Topics: Animals; Endocrine Disruptors; Environmental Exposure; Epithelial Cells; Fungicides, Industrial; Hypothalamo-Hypophyseal System; Insecticides; Male; Maneb; Neonicotinoids; Nitro Compounds; Passeriformes; Thyroid Gland; Thyroxine; Triiodothyronine; Zineb

Cucumbers grown in two different greenhouses were exposed to mancozeb and carbaryl at different times. The effects of 10-day preharvest period, water and detergent washing, peeling, predetermined storage period at 4°C (refrigeration), and fermentation on the reduction of residue levels in the plant tissues were investigated. Mancozeb and carbaryl residues in cucumbers were determined by gas chromatography-electron capture detection. Results showed that residue levels in samples, which were collected after 10 days following the pesticide application, were significantly lower than the samples collected after 2 h subsequent to the pesticide application. The culinary applications were effective in reducing the residue levels of the pesticides in cucumbers. As a result, non-fermentative pickling in sodium chloride and acetic acid was the most effective way to reduce the mancozeb and carbaryl residues of the cucumbers.

Topics: Carbaryl; Cucumis sativus; Fermentation; Food Analysis; Food Contamination; Food Storage; Fruit; Maneb; Pesticide Residues; Zineb

Toxic epidermal necrolysis (TEN) is a life-threatening mucocutaneous disease with high mortality. Dithiocarbamates (DTC) are organosulphur compounds widely used in agriculture, industry and households. We report a case of TEN after exposure to mancozeb in fungicide. A 48-year-old 75 kg b.w. man was admitted with fever and generalized skin/mucous lesions after application of fungicide in a home garden. The patient had necrotic desquamation of gastrointestinal/respiratory tract mucosa, ocular lesion and skin epidermolysis of 90% of body surface. The laboratory findings included elevation of inflammatory parameters, hyperglycaemia, increased urea, creatinine, liver enzymes, hypoalbuminemia and electrolyte disturbances. The treatment included supportive care, management of fluid/electrolyte requirements, analgesics and enteral nutrition. Skin lesions were treated with occlusive non-adhesive biological wound dressings. Due to the proof of Acinetobacter, Escherichia coli and Escherichia faecalis from skin swabs, a combination of meropenem with amikacin was administered. During the next 2 weeks, complete re-epithelialization of skin lesions occurred, mucosal lesions healed and the laboratory parameters returned to normal. The patient was discharged on day 42. TEN is a rare condition that is generally caused by medications. Nevertheless, high attention should be paid to the cases of occupational or household exposure to DTC fungicides widely used in agriculture and home gardens because of their ability to cause TEN after skin and inhalation exposure. Greater emphasis on the hazardous properties of these products is necessary to ensure non-professional users are aware of the necessity of protective clothing during mixing, loading, application and early re-entry into treated fields.

Topics: Environmental Exposure; Fungicides, Industrial; Gardening; Humans; Male; Maneb; Middle Aged; Stevens-Johnson Syndrome; Treatment Outcome; Zineb

A main source of uncertainty currently associated with environmental risk assessment of chemicals is the poor understanding of the influence of environmental factors on the toxicity of xenobiotics. Aiming to reduce this uncertainty, here we evaluate the joint-effects of two pesticides (chlorpyrifos and mancozeb) on the terrestrial isopod Porcellionides pruinosus under different soil moisture regimes. A full factorial design, including three treatments of each pesticide and an untreated control, were performed under different soil moisture regimes: 25%, 50%, and 75% WHC. Our results showed that soil moisture had no effects on isopods survival, at the levels assessed in this experiment, neither regarding single pesticides nor mixture treatments. Additivity was always the most parsimonious result when both pesticides were present. Oppositely, both feeding activity and biomass change showed a higher sensitivity to soil moisture, with isopods generally showing worse performance when exposed to pesticides and dry or moist conditions. Most of the significant differences between soil moisture regimes were found in single pesticide treatments, yet different responses to mixtures could still be distinguished depending on the soil moisture assessed. This study shows that while soil moisture has the potential to influence the effects of the pesticide mixture itself, such effects might become less important in a context of complex combinations of stressors, as the major contribution comes from its individual interaction with each pesticide. Finally, the implications of our results are discussed in light of the current state of environmental risk assessment procedures and some future perspectives are advanced.

Topics: Animals; Chlorpyrifos; Drug Interactions; Feeding Behavior; Isopoda; Maneb; Pesticides; Soil; Soil Pollutants; Water; Zineb

Previous studies in our laboratory have shown that ethylene bisdithiocarbamate (EBDC) fungicides Maneb and Mancozeb are equipotent gastrointestinal toxicants that produce cell loss and metal accumulation within HT-29 and Caco2 colon cells. Nabam, MnCl2, CuCl2 and ZnCl2 exposure produced no loss of viability up to 200 μM and increases in metal levels were noted but not to the same extent as Maneb and Mancozeb. EBDC exposure caused increases in copper levels (20-200 μM). Maneb and Mancozeb treatment also caused increases in manganese and zinc concentrations (20-200 μM). Nabam plus MnCl2 and Nabam and MnCl2 plus ZnCl2 caused decreases in viability and increases in metal levels comparable to Maneb and Mancozeb. Decreases in the ratio of reduced glutathione to glutathione disulfide were observed with Maneb and Mancozeb (20-200 μM). Maneb and Mancozeb treatment results in intracellular metal accumulation leading to the oxidative stress. The metal moiety and the organic portion of EBDCs contribute to toxicity.

Topics: Caco-2 Cells; Cell Survival; Colon; Fungicides, Industrial; HT29 Cells; Humans; Maneb; Metals; Oxidative Stress; Toxicity Tests; Zineb

The widely used fungicide Mancozeb (Man) has been shown to cause genotoxic effects in rodents and toxicological manifestations in different cells, mainly by altering the antioxidant defense in cells. On the other hand, curcumin (Cur), a natural phenolic compound, is thought to possess anti-inflammatory and antioxidant properties. Here, we investigated the possible protective role of Cur on Man-induced toxicity in rat thymocytes and potential mechanism involved. Rat thymocytes were treated with Man(0.01 μg/ml) and/or increasing Cur(0.3, 1, 3 μM) concentrations and levels of cell viability, apoptosis, mitochondrial membrane potential (MMP),Bcl-2, Bax protein expression, caspase-3 and -9 activity and p38 MAPK signaling involvement were examined. Cells treated with Man displayed increased cell toxicity, hypodiploid cells, caspase-3 and -9 activity, Bax protein expression, followed with decreased MMP and Bcl-2 protein expression. Inhibition of p38 MAPK signaling pathway markedly reduced apoptosis rate and caspase-3 activity in thymocytes exposed to Man. Application of increasing Cur (1, 3 μM) concentrations resulted with significantly reduced cytotoxicity, apoptosis, caspase-3, -9 activity, Bax protein expression, together with increased MMP and Bcl-2 protein expression in rat thymocytes. These result suggest that certain Cur concentrations may mediate Man-induced rat thymocytes toxicity through mitochondrial survival pathway, which may be useful in preventing possible secondary immunological consequences induced by Man.

Topics: Animals; Cells, Cultured; Curcumin; Dose-Response Relationship, Drug; Fungicides, Industrial; Male; Maneb; Mitochondria; Rats; Thymocytes; Zineb

Pesticides used for crop protection cause life-threatening diseases affecting the immune system of non-target organisms including birds and mammals. Functionality of immune system is age-dependent; early- as well as old-life stages are more susceptible to toxic exposures because of less competent immune system. Vitamins are so far known to reduce toxic effect of several pesticides and/or xenobiotics. The present in vitro study elucidated immunotoxicity of fungicide mancozeb through comparable stages of immune system maturation in mice (1, 3, and 12months) and chicks (4, 8, and 11weeks). In vitro splenocytes viability on exposure to mancozeb was quantitatively assessed by MTT assay and qualitatively by acridine orange and ethidium bromide (AO/EB) double fluorescence staining. Mancozeb exposure dose dependently (250, 500, 1000, 2500, 5000 and 10,000ng/ml) decreased the splenocytes viability. The in vitro preventive effect of Vitamin E has also been explored on toxicity induced by mancozeb. The increased susceptibility observed both in early and aged groups was due to less/decline competence of the immune system.

Topics: Animals; Cell Survival; Chickens; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Male; Maneb; Mice; Protective Agents; Spleen; Vitamin E; Zineb

The complex immune system displays a coordinated transcriptional response to xenobiotic exposure by altering expression of designated transcription factors that, in turn, trigger immune responses. Despite the identification of several transcription factors that contribute to regulatory response, very little is known about the specific role of factors that are triggered due to exposure to obnoxious pesticides. Here, for the first time, alterations in human peripheral blood lymphocyte expression of transcriptional factors - thrombospondin-1 (THBS-1), secretory phospho-protein-1 (SPP-1), glycoprotein non-metastatic-β (GPNMB) and fasciculation and elongation factor ζ-1 (FEZ-1), due to in vitro exposure to the crop protection chemicals cypermethrin and mancozeb are reported. Results revealed significant changes in expression profiles due to mancozeb exposure, supporting its immune dysfunction potential; in contrast, cypermethrin exposure did not cause significant changes. Based on these effects on gene expression across the doses tested, it was likely key components of immune mechanisms such as proliferation, cell adhesion, apoptosis and cell activation in human PBMC were affected. Although these data are from in vitro experiments, the results point out the potential role for changes in these factors in the etiology of defective T-cell immune function seen in humans occupationally exposed to crop protection chemicals like mancozeb. These studies suggest the involvement of transcription factors in regulation of pesticide-induced immune dysfunction; these studies also represent a novel approach for identifying potential immune-related dysfunctions due to exposure to pesticides. Further studies are needed to better understand the functional significance of these in vitro findings.

Topics: Adaptor Proteins, Signal Transducing; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation; Humans; Leukocytes, Mononuclear; Maneb; Membrane Glycoproteins; Nerve Tissue Proteins; Osteopontin; Pesticides; Pyrethrins; T-Lymphocytes; Thrombospondin 1; Thrombospondins; Transcriptional Activation; Zineb

Mancozeb, a manganese/zinc ethylene-bis-dithiocarbamate, is a fungicide routinely used in pest control programs. However, it has been found to have deleterious effects on human health and on the environment. Indeed, its massive use has raised the issue of possible health risks for agrarian communities; the molecule can also reach human cells via the food chain and alter metabolism, endocrine activity and cell survival. In particular, mancozeb induces many toxic effects on hepatic cell metabolism. For this reason, we investigated its effect in an in vitro model of hepatic damage, namely fatty acid-induced nonalcoholic fatty liver disease in the HepG2 cell line. We found that the hepatic toxicity of the fungicide exacerbated fatty acid-induced steatosis, as manifested by an increase in intracellular lipid droplet accumulation. Furthermore, mancozeb altered cell metabolism and induced cell death through upregulation of lactate dehydrogenase and cytochrome c, respectively, in dose-dependent manners. Therefore, mancozeb may play an important role in the pathogenesis and progression of chronic disease in humans and represents a danger for human health in high doses.

Topics: Cell Survival; Cytochromes c; Fungicides, Industrial; Hep G2 Cells; Humans; L-Lactate Dehydrogenase; Lipid Metabolism; Maneb; Non-alcoholic Fatty Liver Disease; Zineb

The objective of the study was to examine the association between occupational exposure to pesticides and cutaneous melanoma, controlling for all possible confounders.. A pooled analysis of two case-control studies was conducted in two different geographic areas (Italy and Brazil). Detailed pesticides exposure histories were obtained.. Ever use of any pesticide was associated with a high risk of cutaneous melanoma (odds ratio 2.58; 95% confidence interval 1.18-5.65) in particular exposure to herbicides (glyphosate) and fungicides (mancozeb, maneb), after controlling for confounding factors. When subjects were exposed to both pesticides and occupational sun exposure, the risk increased even more (odds ratio 4.68; 95% confidence interval 1.29-17.0).. The study suggests an augmented risk of cutaneous melanoma among subjects with exposure to pesticides, in particular among those exposed to occupational sun exposure.

Topics: Adult; Aged; Brazil; Case-Control Studies; Female; Fungicides, Industrial; Glycine; Glyphosate; Herbicides; Humans; Italy; Male; Maneb; Melanoma; Middle Aged; Occupational Diseases; Occupational Exposure; Odds Ratio; Pesticides; Risk Factors; Skin Neoplasms; Sunlight; Surveys and Questionnaires; Young Adult; Zineb

Mancozeb (MZ), a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Toxicologic studies in mammals and mammalian cells indicate that this fungicide can cause neurological and cytological disorders, putatively associated with pro-oxidant and apoptotic effects. Yeast adaptation to sub-inhibitory concentrations of MZ has been correlated with oxidative response, proteins degradation, and energy metabolism, and its main effect on yeast has been attributed to its high reactivity with thiol groups in proteins. Herein, we show that acute MZ treatments on aerobic exponentially growing yeast of wild type (BY4741) and deletion mutant strains, coupled with multiplex flow cytometry analysis, conclusively demonstrated that MZ displays the typical features of pro-oxidant activity on Saccharomyces, elevating mitochondrial ROS, and causing hyper-polarization of mitochondrial membranes leading to apoptosis. A drastic reduction of cellular viability associated with the maintenance of cell membrane integrity, as well as phosphatidyl serine externalization on yeast cells exposed to MZ, also supports an apoptotic mode of action. Moreover, abrogation of the apoptotic response in yca1 deficient mutants indicates that metacaspase-1 is involved in the programmed cell death mechanism induced by MZ in yeast.

Topics: Apoptosis; Cell Survival; Cysteine Endopeptidases; Fungicides, Industrial; Maneb; Mitochondria; Reactive Oxygen Species; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Zineb

The occurrence of pesticides in groundwater represents an important health issue, notably for population whose drinking water supply source is located in agricultural areas. However, few solutions have been considered with regard to this issue. We tested the efficacy of a vegetal filtering system made of shrub willows planted at a high density (16,000 plants ha(-1)) to filter or degrade pesticides found in the groundwater flowing out of an apple orchard. Ethylene urea (EU), ethylene thiourea (ETU), tetrahydrophthalimide (THPI), atrazine, and desethylatrazine were monitored in the soil solution in willow and control plots over one growing season. ETU and atrazine concentrations were lower in the willow plots relative to the control plots, whereas desethylatrazine concentration was higher in the willow plots. No significant difference was detected for EU and THPI. Furthermore, pesticide concentrations displayed complex temporal patterns. These results suggest that willow filter systems can filter or degrade pesticides, notably ETU and atrazine, and could be used for phytoremediation purposes. Yet, this potential remains to be quantified with further studies using experimental settings allowing more estimation in time and space.

Topics: Biodegradation, Environmental; Captan; Crops, Agricultural; Drinking Water; Fungicides, Industrial; Groundwater; Malus; Maneb; Quebec; Salix; Soil Pollutants; Water Pollutants, Chemical; Zineb

Elevated manganese (Mn) in drinking water has been reported worldwide. While, naturally occurring Mn in groundwater is generally the major source, anthropogenic contamination by Mn-containing fungicides such as mancozeb may also occur. The main objective of this study was to examine factors associated with Mn and ethylenethiourea (ETU), a degradation product of mancozeb, in drinking water samples from villages situated near banana plantations with aerial spraying of mancozeb. Drinking water samples (n = 126) were obtained from 124 homes of women participating in the Infants' Environmental Health Study (ISA, for its acronym in Spanish), living nearby large-scale banana plantations. Concentrations of Mn, iron (Fe), arsenic (As), lead (Pb), cadmium (Cd) and ethylenethiourea (ETU), a degradation product of mancozeb, were measured in water samples. Only six percent of samples had detectable ETU concentrations (limit of detection (LOD) = 0.15 μg/L), whereas 94% of the samples had detectable Mn (LOD = 0.05 μg/L). Mn concentrations were higher than 100 and 500 μg/L in 22% and 7% of the samples, respectively. Mn was highest in samples from private and banana farm wells. Distance from a banana plantation was inversely associated with Mn concentrations, with a 61.5% decrease (95% CI: -97.0, -26.0) in Mn concentrations for each km increase in distance. Mn concentrations in water transported with trucks from one village to another were almost 1000 times higher than Mn in water obtained from taps in houses supplied by the same well but not transported, indicating environmental Mn contamination. Elevated Mn in drinking water may be partly explained by aerial spraying of mancozeb; however, naturally occurring Mn in groundwater, and intensive agriculture may also contribute. Drinking water risk assessment for mancozeb should consider Mn as a health hazard. The findings of this study evidence the need for health-based World Health Organization (WHO) guidelines on Mn in drinking water.

Topics: Adult; Age Factors; Agriculture; Air Pollutants; Costa Rica; Drinking Water; Environmental Health; Environmental Monitoring; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Maneb; Manganese; Musa; Socioeconomic Factors; Young Adult; Zineb

Lup-20(29)-en-3H-ol (Lupeol), a dietary pentacyclic triterpenoid has been shown to possess multiple medicinal activities including anti-inflammatory, anti-oxidant and anti-carcinogenic effects. Mancozeb is a widely used broad-spectrum fungicide with well-known carcinogenic hazards in rodents.. The present study has been designed to investigate the protective effects of lupeol against mancozeb-induced genotoxicity and apoptosis in cultured human lymphocytes (CHLs).. The genotoxic effect of mancozeb was evaluated by chromosomal aberration and micronucleus assays. The cell cycle kinetics and intracellular reactive oxygen species (ROS) generation was measured by flow cytometry. The levels of anti-oxidant enzymes and lipid peroxidation (LPO) were estimated by enzymatic assays. The localization of p65NF-κB was measured by immunocytochemical analysis. The differential expression of genes associated with genotoxicity was measured by qRT-PCR.. Mancozeb exposure (5µg/ml) for 24h caused significant induction of chromosomal aberrations (CAs) and micronuclei (MN) formation in CHLs. Pre-and post-treatment (25 and 50µg/ml) of lupeol for 24h significantly (p<0.05) reduced the frequency of CAs and MN induction, in a dose-dependent manner in mancozeb treated CHLs. Concomitantly, lupeol pre-treatment for 24h significantly increased the levels of anti-oxidant enzymes, superoxide dismutase (SOD) and catalase and decreased ROS generation and LPO. Additionally, lupeol pre-treatment significantly reduced mancozeb-induced apoptosis as shown by Sub-G1 peak analysis and annexin V-PI assay, in a dose dependent manner. Moreover, pre-treatment with lupeol attenuated mancozeb-induced NF-κB activation in CHLs. Furthermore, the results of qRT-PCR showed that lupeol pre-treatment significantly (p<0.05) decreased mancozeb-induced expression of DNA damage (p53, MDM2, COX-2, GADD45α and p21) and increased expression of DNA repair responsive genes (hOGG1 and XRCC1) in CHLs.. Taken together, our findings suggest that lupeol could attenuate mancozeb-induced oxidative stress, which in turn could inhibit NF-κB activation and thus provide protection against mancozeb-induced genotoxicity and apoptosis. So, lupeol could be used as a potent anti-oxidant regimen against pesticide induced genotoxicity in agricultural farm workers.

Topics: Activation, Metabolic; Antimutagenic Agents; Antioxidants; Apoptosis; Cells, Cultured; Chromosome Aberrations; DNA Damage; Fungicides, Industrial; Humans; Lymphocytes; Maneb; Micronucleus Tests; Mutagens; NF-kappa B; Pentacyclic Triterpenes; Zineb

The binding study of pesticides with proteins is of great importance in ecotoxicology. In this study, a comparative interaction mechanism of phytocystatin with three pesticides has been presented, each from a different class-glyphosate herbicide (GPS), chlorpyrifos insecticide (CPF), and mancozeb fungicide (MCZ). The interaction of purified chickpea cystatin (CPC) has been characterized by fluorescence, UV, and circular dichroism (CD) spectroscopic methods. The study revealed association constants (Ka) of 52 M(-1), 1.145 × 10(3) M(-1), and 36.12 M(-1) for the interaction of CPF, MCZ, and GPS with CPC, respectively, signifying the high affinity interaction for MCZ. Structural changes (at tertiary and secondary levels) were confirmed by UV-visible, intrinsic fluorescence and CD spectroscopy. The results showed that the effect on the CPC structure was more pronounced in the case of MCZ, which was followed by CPF and then GPS. The functional analysis of the pesticide treated inhibitor showed a decline in antipapain activity which varied with the time and dose as well as the class of pesticide. MCZ was relatively much more toxic as compared to CPF and GPS. Reactive oxygen species responsible for inhibitor damage were also analyzed. The results obtained implicate that the exposure of plants to pesticides may lead to physicochemical changes in proteins such as phytocystatins leading to physiological damage to the plant system.

Topics: Animals; Chlorpyrifos; Cicer; Cystatins; Glycine; Glyphosate; Maneb; Pesticides; Reactive Oxygen Species; Zineb

Controlled release (CR) nano-formulations of Mancozeb (manganese-zinc double salt of N,N-bisdithiocarbamic acid), a protective fungicide, have been prepared using laboratory-synthesized poly(ethylene glycols) (PEGs)-based functionalized amphiphilic copolymers without using any surfactants or external additives. The release kinetics of the developed Mancozeb CR formulations were studied and compared with that of commercially available 42% suspension concentrate and 75% wettable powder. Maximum amount of Mancozeb was released on 42nd day for PEG-600 and octyl chain, PEG-1000 and octyl chain, and PEG-600 and hexadecyl chain, on 35th day for PEG-1000 and hexadecyl chain, on 28th day for PEG-1500 and octyl chain, PEG-2000 and octyl chain, PEG-1500 and hexadecyl chain, and PEG-2000 and hexadecyl chain in comparison to both commercial formulations (15th day). The diffusion exponent (n value) of Mancozeb in water ranged from 0.42 to 0.62 in tested formulations. The half-release (t

Topics: Alternaria; Basidiomycota; Chemistry Techniques, Synthetic; Delayed-Action Preparations; Diffusion; Fungicides, Industrial; Kinetics; Maneb; Nanocomposites; Polyethylene Glycols; Water; Zineb

Certain pesticides may affect children's neurodevelopment. We assessed whether pesticide exposure was associated with impaired neurobehavioral outcomes in children aged 6-9 years. We conducted a cross-sectional study in 140 children living near banana plantations and plantain farms in the Talamanca County, Costa Rica and assessed their neurobehavioral performance. Exposure was determined by analyzing urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), mancozeb (ethylenethiourea, ETU), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). Repeated urine samples were obtained for 36 children. We estimated associations of pesticide concentrations with neurobehavioral outcomes using multivariable linear and logistic regression models. Median (25th-75th percentiles) TCPy, ETU, and 3-PBA concentrations were 1.4 (.7-3.1), 1.2 (.7-3.0), and .8 (.5-1.5) μg/L, respectively. Intraclass correlation coefficients (ICC) ranged between .32 and .67. After adjustment for potential confounders, higher urinary TCPy concentrations were associated with poorer working memory in boys (n = 59) (β per 10-fold increase in TCPy concentrations = -7.5, 95% CI: -14.4, -.7); poorer visual motor coordination (β = -1.4, 95% CI: -2.7, -.1); increased prevalence of parent-reported cognitive problems/inattention (adjusted OR per 10-fold increase in urinary concentrations = 5.8, 95% CI: 1.6, 22.9), oppositional disorders (aOR = 3.9, 95% CI: 1.0, 16.0), and ADHD (aOR = 6.8, 95% CI: 1.8, 28.6), and; decreased ability to discriminate colors (aOR = 6.6, 95% CI: 1.6, 30.3; the higher the score the worse). Higher ETU concentrations were associated with poorer verbal learning outcomes (β = -7.0, 95% CI: -12.7, -1.3). Higher 3-PBA concentrations were associated with poorer processing speed scores, particularly in girls (β = -8.8, 95% CI: -16.1, -1.4). Our findings indicate that children living near banana and plantain plantations are exposed to pesticides that may affect their neurodevelopment, which for certain domains may differ between boys and girls. We recommend the implementation of measures to reduce pesticide exposure in children living nearby banana plantations.

Topics: Benzoates; Central Nervous System; Child; Child Behavior; Chlorpyrifos; Costa Rica; Cross-Sectional Studies; Female; Humans; Male; Maneb; Pesticides; Pyridones; Zineb

A supervised field trial was conducted at four different agroclimatic locations in India to evaluate the dissipation pattern and risk assessment of carbendazim and mancozeb in mango fruits following foliar application of mixed formulation of carbendazim 12% and mancozeb 63% fungicide (SAAF-75WP) at recommended dose (90 + 472.5) and double the recommended dose (180 + 945 g a.i. ha(-1)). Average initial deposition of carbendazim was in the range of 1.12 to 2.7 and 1.95 to 4.09 mg kg(-1) and for mancozeb in the range of 2.25 to 2.71 and 4.17 to 5.96 mg kg(-1), given at respective doses. Residues of carbendazim and mancozeb were dissipated to the below detectable limit 7 days after spray at recommended dosage in all the locations. The fungicide degradation followed a first order kinetics with half-lives of 1-5 and 1-3 days, for carbendazim and mancozeb, respectively. The TMRC values, calculated from residue data generated from all four locations, were found to be below the MPI in mango fruit, and hence, the fungicide will not cause any adverse effect after consumption of mango fruits. This data could provide guidance for the proper and safe use of this fungicide mixture for managing disease incidence in mango in India.

Topics: Benzimidazoles; Carbamates; Environmental Monitoring; Fruit; Fungicides, Industrial; Half-Life; India; Kinetics; Maneb; Mangifera; Pesticide Residues; Risk Assessment; Zineb

Thyroid is an important homeostatic regulator of metabolic activities as well as endocrine mechanisms including those of reproduction. Present investigation elucidated the thyroid disrupting potential of a neonicotinoid imidacloprid and a dithiocarbamate mancozeb in a seasonally breeding wildlife bird, Red Munia (Amandava amandava) who is vulnerable to these two pesticides through diet (seed grains and small insects). Adult male birds were exposed to 0.5% LD50 mgkg(-1)bwd(-1) of both the pesticides through food for 30days during the preparatory and breeding phases. Weight, volume and histopathology of thyroid gland were distinctly altered. Disruption of thyroid follicles reflected in nucleus-to-cytoplasm ratio (N/C) in epithelial and stromal cells, epithelial cell hypertrophy and altered colloid volume. Impairment of thyroid axis was pesticide and phase specific as evident from the plasma levels of thyroid (T4 and T3) and pituitary (TSH) hormones. In preparatory phase, plasma TSH was increased in response to decrease of T4 on mancozeb exposure showing responsiveness of the hypothalamic-pituitary-thyroid (HPT) axis to feedback regulation. On imidacloprid exposure, however, plasma levels of both T4 and TSH were decreased indicating non-functioning of negative feedback mechanism. Increased plasma T3 in response to both the pesticides exposure might be due to synthesis from non-thyroidal source(s) in a compensatory response to decrease level of T4. In breeding phase, impairment of HPT axis was more pronounced as plasma T4, T3 and TSH were significantly decreased in response to both mancozeb and imidacloprid. Thus, low dose pesticide exposure could affect the thyroid homeostasis and reproduction.

Topics: Animals; Body Weight; Cell Nucleus Size; Environmental Exposure; Environmental Monitoring; Epithelial Cells; Fungicides, Industrial; Imidazoles; Male; Maneb; Neonicotinoids; Nitro Compounds; Organ Size; Passeriformes; Pituitary Gland; Stromal Cells; Thyroid Gland; Thyroid Hormones; Thyrotropin; Zineb

Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological manifestations in different cells, mainly by generation of free radicals which may alter antioxidant defence systems in cells. The effect of mancozeb on the cells of a primary lymphoid organ has not been studied. In the present study, the effects of mancozeb (0.2, 2 and 5 μg/ml) or mancozeb+ascorbic acid (100 μg/ml), or ascorbic acid alone or control medium alone on the levels of cell viability, apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro. Cells treated with mancozeb displayed a concentration-dependent increase of hypodiploid cells and ROS production followed by markedly decreased viability of the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced cytotoxicity in cell cultures treated with 0.2 and 2 μg/ml of mancozeb, together with significantly decreased ROS levels and increased MMP and ATP levels. In cells treated with 5 μg/ml of mancozeb, ascorbic acid failed to reduce toxicity while simultaneously increasing the apoptosis rate of thymocytes. These results suggest that ROS plays a significant role in mancozeb-induced toxicity, through alteration of mitochondrial function. Ascorbic acid administration reduced the toxicity rate in cells treated with lower mancozeb concentrations, while it may have the ability to shift cells from necrosis to apoptosis in the presence of highest mancozeb concentrations.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Apoptosis; Ascorbic Acid; Biomarkers; Cell Survival; Cells, Cultured; Fungicides, Industrial; Male; Maneb; Membrane Potential, Mitochondrial; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Thymocytes; Zineb

Mancozeb (MZ) is a fungicide that belongs to the subclass of metal (Mn/Zn) ethylene-bis-dithiocarbamate pesticides. In mouse and human granulosa cells (GCs) exposed to MZ (0.01 μg/ml), morphological modifications and significant alterations of p53 expression level in comparison with control GCs were recorded.. To investigate if MZ (0.01 μg/ml) induces oxidative stress and alters energy metabolism in exposed mouse GCs.. Following fungicide exposure, GCs showed low p53 content, a depolarized mitochondrial membrane potential (ΔΨm), as well as low ATP and reduced glutathione (GSH) levels associated with increased reactive oxygen species (ROS) generation. No remarkable differences on other parameters such as ATP/ADP ratio, energy charge, as well as induction of apoptosis and DNA damage were found. The activation of AKT and PDK1 kinases in MZ-treated cells was observed. Inhibition of ROS generation by the antioxidant N-acetylcysteine (NAC) restored a normal expression level of p53.. Our results demonstrate that the low dose of MZ here used induces a mild oxidative stress in GCs, and provides evidence for the possible involvement of AKT/PKB signaling pathway in triggering adaptive and survival response.

Topics: Adenosine Triphosphate; Animals; Cells, Cultured; DNA Damage; Female; Fungicides, Industrial; Glutathione; Granulosa Cells; Maneb; Mice; Mitochondria; Oxidation-Reduction; Oxidative Stress; Proto-Oncogene Proteins c-akt; Tumor Suppressor Protein p53; Zineb

The impact of the fungicides mancozeb, myclobutanil, and meptyldinocap on populations of Typhlodromus pyri Scheuten was evaluated under field conditions, when applied following the good agricultural practices recommended for their use. Two complementary statistical models were used to analyze the population reduction compared to the control: a linear mixed model to estimate the mean effect of the fungicide, and a generalized linear mixed model (proportional odds mixed model) to estimate the cumulative probability for those effects being equal or less than a specific IOBC class (International Organization for Biological and Integrated Control of Noxious Animal and Plants). Findings from 27 field experiments in a range of different vine-growing regions in Europe indicated that the use of mancozeb, myclobutanil, and meptyldinocap caused minimal impact on naturally occurring populations of T. pyri. Both statistical models confirmed that although adverse effects on T. pyri can occur under certain conditions after several applications of any of the three fungicides studied, the probability of the effects occurring is low and they will not persist. These methods demonstrated how data from a series of trials could be used to evaluate the variability of the effects caused by the chemical rather than relying on the worst-case findings from a single trial.

Topics: Animals; Dinitrobenzenes; Europe; Fungicides, Industrial; Maneb; Mites; Models, Statistical; Nitriles; Triazoles; Vitis; Zineb

Tattoo belongs to the group of carbamate fungicides and contains Mancozeb (ethylene(bis)dithiocarbamate) as its main constituent. The toxicity of Mancozeb to living organisms, particularly fish, is not resolved. This work investigated the effects of 96 h of exposure to 3, 5, or 10 mg L(-1) of Tattoo (corresponding to 0.9, 1.5, or 3 mg L(-1) of Mancozeb) on the levels of oxidative stress markers and the antioxidant enzyme system of brain, liver, and kidney of goldfish, Carassius auratus). In liver, Tattoo exposure resulted in increased activities of superoxide dismutase (SOD) by 70%-79%, catalase by 23%-52% and glutathione peroxidase (GPx) by 49%. The content of protein carbonyls (CP) in liver was also enhanced by 92%-125% indicating extensive damage to proteins. Similar increases in CP levels (by 98%-111%) accompanied by reduced glucose-6-phosphate dehydrogenase activity (by 13%-15%) was observed in kidney of fish exposed to Tattoo; however, SOD activity increased by 37% in this tissue after treatment with 10 mg L(-1) Tattoo. In brain, a rise in lipid peroxide level (by 29%) took place after exposure to 10 mg L(-1) Tattoo and was accompanied by elevation of high-molecular mass thiols (by 14%). Tattoo exposure also resulted in a concentration-dependent decrease in glutathione reductase activity (by 26%-37%) in brain. The data collectively show that exposure of goldfish to 3-10 mg L(-1) of the carbamate fungicide Tattoo resulted in the development of mild oxidative stress and activation of antioxidant defense systems in goldfish tissues.

Topics: Animals; Antioxidants; Brain; Catalase; Fungicides, Industrial; Glucosephosphate Dehydrogenase; Glutathione Peroxidase; Glutathione Reductase; Goldfish; Kidney; Lipid Peroxides; Liver; Maneb; Oxidation-Reduction; Oxidative Stress; Sulfhydryl Compounds; Superoxide Dismutase; Zineb

The determination of transition metal containing dithiocarbamate fungicides represents a challenging aspect of analytical object. They have a low stability, low solubility and stabilize versatile coordination monomers, dimers, disulfides and/or S-oxidized derivatives. Their diverse biological activities and agricultural implementation encompass plant prevention and crop protection against a variety of plants containing fungi and diseases of 400 pathogens and 70 cultures. Nonetheless, those dithiocarbamates (DTCs) are banned for agricultural use in Europe or have expiration at years 2016-2017 because of their highly toxic degradation products and/or metabolites, in particular ethylene thiourea; they found large-scale implementations in materials research and medicine. Despite the broad interdisciplinary of DTC application, due to the above reasons, they have received little attention in the rapidly growing field of analytical chemistry, and in particular, the analytical mass spectrometry. Therefore, the study reported on qualitative, quantitative and structural analysis of ten DTCs (1-10), using the matrix assisted laser desorption/ionization (UV-MALDI)-Orbitrap-mass spectrometry (MS) contributed considerably to the implementation of the method for environmental and foodstuffs monitoring. Its ultrahigh resolving power and capacity for direct solid-state analysis, at limited number of sample pretreatment steps, at concentration levels of analytes of up to femtogram per gram resulted to achievement of a highly precise analytical information for these non-trivial objects. The presented fully validated method and technique is based on the successful ionization of DTCs embedded in three novel organic salts (M1-M3). In this regard, the reported MS and the single-crystal X-ray diffraction data as well as the quantum chemical one are able to correlate the molecular structures in condense and in the gas phase. Despite the novelty of the fundamental methodological character of the research reported, the promising metrology contributed to the applied aspect of the UV-MALDI-MS as a robust analytical method for environmental and foodstuffs monitoring, which is tested on two commercially available crop protecting products such as Mancozeb® and Antracol®, respectively.

Topics: Environmental Monitoring; Europe; Fungicides, Industrial; Maneb; Mass Spectrometry; Metals; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thiocarbamates; Transition Elements; X-Ray Diffraction; Zineb

To compare the side-effects of chemical versus biofungicides on non-target organisms in agricultural soil, a study of population structure, spatial distribution and fecundity of oribatid mites, a diverse and species-rich group of microarthropods indicative of decomposer activity in soil was done. Plots laid out in agricultural fields of a research station in Egypt, were cultivated with cucumber and treated with two chemical fungicides: Ridomil Plus 50% wp (active ingredients=metalaxyl and copper oxychloride) and Dithane M-45 (active ingredient=mancozeb), and two biofungicides: Plant Guard (containing the antagonistic fungus Trichoderma harzianum) and Polyversum (containing the fungi-parasitic oomycete Pythium oligandrum). All treatments were done using both low-volume and high-volume spraying techniques to check whether any effects were dependent on the method of application. Oribatid mite communities were assessed from soil core samples collected during the growing season. Total abundance of oribatids was not different across the plots, but some species decreased in number, while one species increased. Species diversity and community equitability decreased with the application of chemical and biofungicides especially when using high-volume spraying. In control plots most oribatid species showed a significant degree of aggregation, which tended to decrease under fungicide treatment. Ridomil Plus, Plant Guard and Polyversum had a negative effect on the gravid/ungravid ratio of some species. Egg number averaged over the whole adult population was not directly related to the application of chemical and biofungicides but it showed a species-specific relationship with population density. In general biofungicides had a smaller effect on population size and community structure of oribatid mite species than chemical fungicides. The results indicate that biofungicides may be the preferred option when aiming to prevent side-effects on sensitive groups among the species-rich soil detritivore community.

Topics: Agriculture; Alanine; Animals; Biological Control Agents; Biota; Copper; Cucumis sativus; Egypt; Fungicides, Industrial; Maneb; Mites; Population Dynamics; Pythium; Reproduction; Soil; Trichoderma; Zineb

A sensitive and rugged residue analysis method was validated for the estimation of dithiocarbamate fungicides in a variety of fruit and vegetable matrices. The sample preparation method involved reaction of dithiocarbamates with Tin(II) chloride in aqueous HCl. The CS2 produced was absorbed into an isooctane layer and estimated by GC-MS selected ion monitoring. Limit of quantification (LOQ) was ⩽40μgkg(-1) for grape, green chilli, tomato, potato, brinjal, pineapple and chayote and the recoveries were within 75-104% (RSD<15% at LOQ). The method could be satisfactorily applied for analysis of real world samples. Dissipation of mancozeb, the most-used dithiocarbamate fungicide, in field followed first+first order kinetics with pre-harvest intervals of 2 and 4days in brinjal, 7 and 10days in grapes and 0day in chilli at single and double dose of agricultural applications. Cooking practices were effective for removal of mancozeb residues from vegetables.

Topics: Cooking; Food Contamination; Food Safety; Fruit; Fungicides, Industrial; Gas Chromatography-Mass Spectrometry; Maneb; Pesticide Residues; Time Factors; Vegetables; Zineb

This paper describes a proton high resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) metabolomic study of lettuce (Lactuca sativa L.) leaves to characterise metabolic adaptations during leaf growth and exposure to mancozeb. Metabolite variations were identified through multivariate analysis and checked through spectral integration. Lettuce growth was accompanied by activation of energetic metabolism, preferential glucose use and changes in amino acids, phospholipids, ascorbate, nucleotides and nicotinate/nicotinamide. Phenylalanine and polyphenolic variations suggested higher oxidative stress at later growth stages. Exposure to mancozeb induced changes in amino acids, fumarate and malate, suggesting Krebs cycle up-regulation. In tandem disturbances in sugar, phospholipid, nucleotide and nicotinate/nicotinamide metabolism were noted. Additional changes in phenylalanine, dehydroascorbate, tartrate and formate were consistent with a higher demand for anti-oxidant defence mechanisms. Overall, lettuce exposure to mancozeb was shown to have a significant impact on plant metabolism, with mature leaves tending to be more extensively affected than younger leaves.

Topics: Amino Acids; Antioxidants; Citric Acid Cycle; Lactuca; Magnetic Resonance Spectroscopy; Maneb; Metabolome; Pesticides; Plant Leaves; Zineb

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight.

Topics: Animals; Body Mass Index; Body Weight; Computer Simulation; Feeding Behavior; Female; Hormones; Imidazoles; Lipid Metabolism; Lipids; Male; Maneb; Metabolism; Mice; Molecular Docking Simulation; Neonicotinoids; Nitro Compounds; Pesticides; PPAR gamma; Receptors, Thyroid Hormone; Signal Transduction; Zineb

Manganese (Mn), an essential nutrient, is a neurotoxicant at high concentrations. We measured Mn concentrations in repeated blood and hair samples collected from 449 pregnant women living near banana plantations with extensive aerial spraying of Mn-containing fungicide mancozeb in Costa Rica, and examined environmental and lifestyle factors associated with these biomarkers. Mean blood Mn and geometric mean hair Mn concentrations were 24.4 μg/L (8.9-56.3) and 1.8 μg/g (0.05-53.3), respectively. Blood Mn concentrations were positively associated with gestational age at sampling (β = 0.2; 95% CI: 0.1 to 0.2), number of household members (β = 0.4; 95% CI: 0.1 to 0.6), and living in a house made of permeable and difficult-to-clean materials (β = 2.6; 95% CI: 1.3 to 4.0); and inversely related to smoking (β = -3.1; 95% CI: -5.8 to -0.3). Hair Mn concentrations were inversely associated with gestational age at sampling (% change = 0.8; 95% CI: -1.6 to 0.0); and positively associated with living within 50 m of a plantation (% change = 42.1; 95% CI: 14.2 to 76.9) and Mn concentrations in drinking water (% change = 17.5; 95% CI: 12.2 to 22.8). Our findings suggest that pregnant women living near banana plantations aerially sprayed with mancozeb may be environmentally exposed to Mn.

Topics: Adolescent; Adult; Agriculture; Costa Rica; Environmental Exposure; Female; Fungicides, Industrial; Hair; Humans; Maneb; Manganese; Pregnancy; Young Adult; Zineb

Environmental factors have been implicated in the pathogenesis of neurodegenerative diseases. Maneb (MB) and mancozeb (MZ) have been extensively used as pesticides. Exposure to MB lowers the threshold for dopaminergic damage triggered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MB and MZ potentiate 1-methyl-4-phenylpyridium (MPP(+))-induced cytotoxicity in rat pheochromocytoma (PC12) cells partially via nuclear factor kappa B (NF-κB) activation. RTP801 dramatically increased by oxidative stresses and DNA damage is the possible mechanism of neurotoxins-induced cell death in many studies. This study demonstrated that MB and MZ induced DNA damage as seen in comet assay. The expressions of RTP801 protein and mRNA were elevated after MB and MZ exposures. By knocking down RTP801 using shRNA, we demonstrated that NF-κB activation by MB and MZ was regulated by RTP801 and cell death triggered by MB and MZ was associated with RTP801 elevation. This revealed that the toxic mechanisms of dithiocarbamates are via the cross talk between RTP801 and NF-κB.

Topics: Animals; Cell Death; Cell Survival; Comet Assay; Ditiocarb; DNA Damage; Gene Knockdown Techniques; Luciferases; Maneb; Manganese; NF-kappa B; PC12 Cells; Pesticides; Rats; Repressor Proteins; RNA, Small Interfering; Transcription Factors; Transcription, Genetic; Zineb

Polymerization of citric acid onto the surface of oxidized multiwall carbon nanotubes led to MWCNT-graft-poly(citric acid) (MWCNT-g-PCA) hybrid materials. Because of the presence of conjugated citric acid branches, synthesized MWCNT-g-PCA hybrid materials were not only soluble in water but also able to trap water-soluble chemical species and metal ions. Trapping of pesticides such as zineb and mancozeb in aqueous solution by MWCNT-g-PCA hybrid materials led to encapsulated pesticide (EP) in the polycitric acid shell. Optimum conditions for encapsulation of zineb and mancozeb in hyperbranched polycitric acid such as pH, time of stirring, and temperature were investigated by the UV-vis spectroscopy method. Encapsulation of pesticides on CNT-g-PCA hybrid material was confirmed via TEM analysis. Experiments indicated that new the CNT-g-PCA-EP hybrid material in comparison with bulk pesticide had a superior toxic influence on Alternaria alternata fungi.

Topics: Alternaria; Chemistry, Pharmaceutical; Fungicides, Industrial; Maneb; Nanoparticles; Nanotubes, Carbon; Plant Diseases; Polymers; Zineb

Pesticides are used in large amounts in agriculture and the evaluation of their toxic effects is of major concern to public and environmental health. The aim of the present study was to investigate the genotoxic potential of a commercial formulation of the fungicide mancozeb by the micronucleus test in bone marrow and the comet assay in total blood of Wistar rats. Adult male Wistar rats were treated with a solution of mancozeb at a concentration of 40 mg/kg/day, administered intraperitoneally for 18 consecutive days, and compared to a control group. The results indicate that mancozeb induced significantly higher DNA damage as detected by the comet assay and increased the frequency of micronuclei. The results show that mancozeb is genotoxic and may adversely affect the DNA integrity of exposed organisms.

Topics: Animals; Ditiocarb; DNA Damage; Erythrocyte Count; Erythrocytes; Male; Maneb; Micronuclei, Chromosome-Defective; Micronucleus Tests; Rats, Wistar; Zineb

Mancozeb and its main metabolite ethylene thiourea (ETU) may alter thyroid function; thyroid hormones are essential for fetal brain development. In Costa Rica, mancozeb is aerially sprayed at large-scale banana plantations on a weekly basis.. Our goals were to evaluate urinary ETU concentrations in pregnant women living near large-scale banana plantations, compare their estimated daily intake (EDI) with established reference doses (RfDs), and identify factors that predict their urinary ETU concentrations.. We enrolled 451 pregnant women from Matina County, Costa Rica, which has large-scale banana production. We visited 445 women up to three times during pregnancy to obtain urine samples (n = 872) and information on factors that possibly influence exposure. We determined urinary ETU concentrations using liquid chromatography mass spectrometry.. Pregnant women's median urinary ETU concentrations were more than five times higher than those reported for other general populations. Seventy-two percent of the women had EDIs above the RfD. Women who lived closest (1st quartile, < 48 m) to banana plantations on average had a 45% (95% CI: 23, 72%) higher urinary ETU compared with women who lived farthest away (4th quartile, ≥ 565 m). Compared with the other women, ETU was also higher in women who washed agricultural work clothes on the day before sampling (11%; 95% CI: 4.9, 17%), women who worked in agriculture during pregnancy (19%; 95% CI: 9.3, 29%), and immigrant women (6.2%; 95% CI: 1.0, 13%).. The pregnant women's urinary ETU concentrations are of concern, and the principal source of exposure is likely to be aerial spraying of mancozeb. The factors predicting ETU provide insight into possibilities for exposure reduction.

Topics: Adolescent; Adult; Agriculture; Air Pollutants; Costa Rica; Environmental Exposure; Ethylenethiourea; Female; Fungicides, Industrial; Gestational Age; Humans; Maneb; Maternal Exposure; Pregnancy; Prenatal Diagnosis; Zineb

The use of fungicides is the continuous exercise particularly in orchard crops where fungal diseases, such as white root rot, have the potential to destroy horticultural crops rendering them unsaleable. In view of above problem, the present study examines the effect of different concentrations of mancozeb (0-2000 ppm) at different incubation periods for their harmful side effects on various microbiological processes, soil microflora, and soil enzymes in alluvial soil (pH 6.8) collected from apple orchards of Shimla in Himachal Pradesh (India). Low concentrations of mancozeb were found to be deleterious towards fungal and actinomycetes population while higher concentrations (1000 and 2000 ppm) were found to be detrimental to soil bacteria. Mancozeb impaired the process of ammonification and nitrification. Similar results were observed for nitrifying and ammonifying bacteria. Phosphorus solubilization was increased by higher concentration of mancozeb, that is, 250 ppm and above. In unamended soil, microbial biomass carbon and carbon mineralization were adversely affected by mancozeb. Soil enzymes, that is, amylase, invertase, and phosphatase showed adverse and disruptive effect when mancozeb used was above 10 ppm in unamended soil. These results conclude that, to lessen the harmful effects in soil biological processes caused by this fungicide, addition of higher amount of nitrogen based fertilizers is required.

Topics: Bacteria; Fungi; Fungicides, Industrial; India; Maneb; Plant Diseases; Plant Roots; Soil; Soil Microbiology; Zineb

Field experiments were conducted during 2010-11 and 2011-12 to assess the yield losses due to Alternaria blight disease caused by Alternaria lini and A. linicola in recently released cultivars and their management with the integration of Trichoderma viride, fungicides and plant extract. Disease severity on leaves varied from 41.07% (Parvati) to 65.01% (Chambal) while bud damage per cent ranged between 23.56% (Shekhar) to 46.12% (T-397), respectively in different cultivars. Maximum yield loss of 58.44% was recorded in cultivar Neelum followed by Parvati (55.56%), Meera (55.56%) and Chambal (51.72%), respectively while minimum loss was recorded in Kiran (19.99%) and Jeevan (22.22%). Minimum mean disease severity (19.47%) with maximum disease control (69.74%) was recorded with the treatment: seed treatment (ST) with vitavax power (2 g kg(-1) seed) + 2 foliar sprays (FS) of Saaf (a mixture of carbendazim+mancozeb) 0.2% followed by ST with Trichoderma viride (4g kg(-1) seed) + 2 FS of Saaf (0.2%). Minimum bud damage (13.75%) with maximum control (60.94%) was recorded with treatment of ST with vitavax power+2 FS of propiconazole (0.2%). Maximum mean seed yield (1440 kg ha(-1)) with maximum net return (Rs. 15352/ha) and benefit cost ratio (1:11.04) was obtained with treatment ST with vitavax power + 2 FS of Neem leaf extract followed by treatment ST with vitavax power+2 FS of Saaf (1378 kg ha(-1)).

Topics: Aerosols; Alternaria; Alternariosis; Azadirachta; Benzimidazoles; Carbamates; Carboxin; Flax; Fungicides, Industrial; Maneb; Pest Control; Pest Control, Biological; Plant Diseases; Plant Extracts; Plant Leaves; Powders; Triazoles; Trichoderma; Zineb

Mancozeb is a manganese/zinc ethylene-bis-dithiocarbamate fungicide that is widely used in agriculture to control a broad variety of fungal infections of both vegetables and ornamental plants. The present study has been carried out to investigate the possible effect of mancozeb on animal the oxidative stress and some of the biochemical markers in male Wistar rats. In this experiment, adult male rats weighing between 200 and 250 g were treated per os for 4 weeks with two different doses of 800 and 1200 mg/kg per day. Reduced glutathione (GSH) levels were decreased in all treated groups compared to control ones. It has been observed a significant increase in the fresh weight of liver in individuals of both doses. Moreover, mancozeb exposure caused a significant (p < 0.05) fall in aspartic aminotransferase (AST) and alanine aminotransferase (ALT) in group treated with 1200 and 800 mg/kg/day. Similarly, alkaline phosphatase (ALP) activity underwent a significant (p < 0.05) increase in both groups. The obtained observations clearly reveal hepatotoxic effects of mancozeb in rats and constitute, therefore, an environmental health risks to living organisms.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biological Assay; Fungicides, Industrial; Glutathione; Liver; Male; Maneb; Oxidative Stress; Rats; Rats, Wistar; Zineb

Mancozeb is a fungicide belonging to the ethylene-bisdithiocarbamate group and is widely used in agriculture. The aim of this study was to examine the protective effect of quercetin (QRN) against oxidative stress induced by mancozeb in human erythrocytes. In order to verify this, 5 ml of venous blood was collected and the erythrocytes were separated and divided into equal parts. One part was incubated with different concentrations of mancozeb (0, 10, 30, 100 µM) for 4 h at 37°C. The other part was preincubated with QRN (40 and 80 μM) for 30 min, followed by mancozeb (0, 10, 30, 100 µM) incubation for 4 h. We found reduction in the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) along with elevated levels of lipid peroxide (LPO) in erythrocytes incubated with 30 and 100 µm of mancozeb. Pre-incubation with QRN (80 μM) reversed oxidative stress induced by mancozeb (30 μM) and inhibited LPO induced at 100 μM by 64.36%. QRN also reduced the haemolytic effect on erythrocytes but could not prevent the induction of haemolysis by mancozeb. Therefore, these results suggest that QRN may play a role in preventing the oxidative stress induced by mancozeb in human erythrocytes.

Topics: Adult; Catalase; Dose-Response Relationship, Drug; Erythrocytes; Female; Fungicides, Industrial; Glutathione; Hemoglobins; Humans; Lipid Peroxides; Male; Maneb; Oxidative Stress; Quercetin; Superoxide Dismutase; Zineb

Mancozeb (manganese/zinc ethylene bis-dithiocarbamate) is an organometallic fungicide that has been associated with human neurotoxicity and neurodegeneration. In a high-throughput screen for modulators of KCNQ2 channel, a fundamental player modulating neuronal excitability, Mancozeb, was found to significantly potentiate KCNQ2 activity. Mancozeb was validated electrophysiologically as a KCNQ2 activator with an EC50 value of 0.92±0.23μM. Further examination showed that manganese but not zinc ethylene bis-dithiocarbamate is the active component for the positive modulation effects. In addition, the compounds are effective when the metal ions are substituted by iron but lack potentiation activity when the metal ions are substituted by sodium, signifying the importance of the metal ion. However, the iron (Fe(3+)) alone, organic ligands alone or the mixture of iron with the organic ligand did not show any potentiation effect, suggesting as the active ingredient is a specific complex rather than two separate additive or synergistic components. Our study suggests that potentiation on KCNQ2 potassium channels might be the possible mechanism of Mancozeb toxicity in the nervous system.

Topics: Action Potentials; Animals; CHO Cells; Cricetinae; Dose-Response Relationship, Drug; Electrophysiological Phenomena; Fungicides, Industrial; KCNQ2 Potassium Channel; Maneb; Manganese; Zinc; Zineb

Humans are exposed to various chemical mixtures daily. The toxic response to a mixture of chemicals could be potentiated or suppressed. This study demonstrates that non-toxic doses of pesticides can induce cellular changes that increase cell sensitivity to other toxins or stress. Pesticide exposure is an environmental risk factor for Parkinson's disease. Manganese (Mn) is essential but high dose exposure may results in neurological dysfunction. Mn-containing dithiocarbamates, maneb (MB) and mancozeb (MZ), are primarily used as pesticides. Studies have shown that MB can augment dopaminergic damage triggered by sub-toxic doses of Parkinsonian mimetic MPTP. However, the mechanism underlying this effect is not clear. Activation of nuclear factor kappa B (NF-κB) has been implicated in MPTP toxicity. Mn stimulates the activation of NF-κB and subsequently induces neuronal injury via an NF-κB dependent mechanism. We speculate that MB and MZ enhance MPTP active metabolite (methyl-4-phenylpyridine ion, MPP(+)) toxicity by activating NF-κB. The activation of NF-κB was observed using Western blot analysis and NF-κB response element driven Luciferase reporter assay. Western blot data demonstrated the nuclear translocation of NF-κB p65 and the degradation of IkBα after MB and MZ 4-h treatments. Results of NF-κB response element luciferase reporter assay confirmed that MB and MZ activated NF-κB. The NF-κB inhibitor (SN50) was also shown to alleviate cytotoxicity induced by co-treatment of MB or MZ and MPP(+). This study demonstrates that activation of NF-κB is responsible for the potentiated toxic effect of MB and MZ on MPP(+) induced cytotoxicity.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Cell Death; Cell Survival; Ditiocarb; Luciferases; Maneb; Manganese; NF-kappa B; Parkinson Disease; PC12 Cells; Peptides; Rats; Response Elements; Signal Transduction; Zineb

The dynamics and residues of mixed formulation of fenamidone and mancozeb in a gherkin field ecosystem were investigated. The quantification was performed using gas chromatography-electron capture detection (GC-ECD) and UV-vis spectrophotometry for fenamidone and mancozeb residues, respectively. The method was validated using blank samples spiked at three levels and the results showed that recoveries ranged from 92 to 98 and 90 to 96 percent with relative standard deviations (RSD) ranging of 0.78-5.9 and 2.04-4.41 percent for fenamidone and mancozeb, respectively. The compound degradation followed a first order kinetics with half-lives of 2.8-2.82 and 2.02-2.26 days, for fenamidone and mancozeb, respectively. Pesticide residues in fruit were below the EU maximum residue level (MRL) after 10 days for fenamidone (0.02 µg/g) and just after treatment for mancozeb (2 µg/g). These results can be utilized in formulating the spray schedule and safety evaluation for these pesticides in gherkin.

Topics: Chromatography, Gas; Cucumis; Ecosystem; Fruit; Fungicides, Industrial; Imidazolines; Kinetics; Maneb; Pesticide Residues; Strobilurins; Zineb

To compare workplace characteristics, workplace behaviors, and the health beliefs of female farmworkers of childbearing age with actual biomarkers of exposure to organophosphate pesticides and to the fungicide mancozeb.. Hispanic and Haitian farmworkers between the ages of 18 and 40 years working in nursery or fernery operations were recruited to participate in a cross-sectional survey, examining demographics, work practices, work-related hygiene, and pesticide exposure beliefs. Single-void (spot) urine samples were analyzed for organophosphate and ethylenethiourea metabolites.. Women in nurseries worried less frequently about the effects of pesticides on their health than those in fernery operations. In summary, organophosphate and ethylenethiourea levels in nursery workers were significantly higher than levels in fernery workers and the control group.. Results showed that perceived pesticide exposure did not correspond to actual metabolite levels within differing agricultural subpopulations.

Topics: Adult; Agriculture; Biomarkers; Cross-Sectional Studies; Ethylenethiourea; Female; Florida; Fungicides, Industrial; Haiti; Health Knowledge, Attitudes, Practice; Hispanic or Latino; Humans; Hygiene; Insecticides; Maneb; Occupational Exposure; Organophosphates; Perception; Workplace; Zineb

Pesticide residues remaining on food represent a potential risk to consumer's health. Determination of these pesticide residues involves tedious procedures of analysis with regard to time and laboratory work. Near-infrared spectroscopy (NIRS) is a possible alternative to these methods. The aim of this research was to evaluate the ability of NIRS to classify two pesticides used for controlling apple fruit pests according to their concentration. Different solutions were prepared, based on the dose recommended by the pesticide producers for apple pest treatments. Spectra were acquired on a spectrophotometer from liquid samples belonging to these solutions.. Calibration models were developed from liquid samples, following the soft independent modelling of class analogy (SIMCA) analysis method. These models classified between 99 and 100% of the validation samples belonging to different pesticide concentration solutions even at the maximum residue limit level of these products in apple fruit.. NIRS technology shows a high potential for identifying pesticides in liquid samples, according to their concentration, at the levels required by the legislation.

Topics: Fungicides, Industrial; Malus; Maneb; Pesticide Residues; Spectroscopy, Near-Infrared; Zineb

Manganese-containing fungicides like Mancozeb have been associated with neurodegenerative conditions like Parkinson's disease. We examined the behavioral damage and differential neuronal vulnerability resulting from Mancozeb exposure using Caenorhabditis elegans, an important mid-trophic level soil organism that is also a powerful model for studying mechanisms of environmental pollutant-induced neurodegenerative disease. The dopamine-mediated swim to crawl locomotory transition behavior is exquisitely vulnerable to Mancozeb, with functional impairment preceding markers of neuronal structural damage. The damage is partially rescued in mutants lacking the divalent metal transporter, SMF-1, demonstrating that some, but not all, of the damage is mediated by manganese. Increasing concentrations of Mancozeb recruit additional behavioral dysfunction, notably serotonin-mediated egg-laying behavior, but without evident serotonergic neuronal structural damage. Thus, measurements of behavioral dysfunction are a sensitive early marker of fungicide toxicity that could be exploited to examine further mechanisms of neuron damage and possible therapeutic interventions. These results also provide important insight into the consequences of fungicide use on the ecological behavior of nematodes.

Topics: Animals; Behavior, Animal; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cation Transport Proteins; Dopamine; Dose-Response Relationship, Drug; Environmental Pollutants; Fungicides, Industrial; Locomotion; Maneb; Mechanotransduction, Cellular; Mutation; Nerve Degeneration; Neurons; Oviposition; Serotonin; Touch; Zineb

Dissipation of mancozeb and metalaxyl in tomato was estimated following four applications of a combination formulation Ridomil MZ (mancozeb 64% + metalaxyl 8%) at 0.25 and 0.50% at 10 days interval by carbon disulphide evolution method and gas liquid chromatography with nitrogen phosphorous detector, respectively. Half-life periods for mancozeb were 3.76 and 4.14 days, whereas for metalaxyl these values were 1.29 and 0.41 days at single and double the application rates, respectively. Residues of mancozeb dissipated below limit of quantification (LOQ) of 0.25 mg kg(-1) after 10 and 15 days at single and double the application dosage, respectively. Similarly, residues of metalaxyl took 3 and 5 days to reach LOQ of 0.02 mg kg(-1), at single and double dosages, respectively.

Topics: Alanine; Chromatography, Gas; Half-Life; Limit of Detection; Maneb; Pesticide Residues; Solanum lycopersicum; Zineb

Most agronomic situations involve a sequence of herbicide, fungicide, and insecticide application. On the other hand, use of pesticidal combinations has become a standard practice in the production of many agricultural crops. One of the most important processes influencing the behavior of a pesticide in the environment is its degradation in soil. It is known that due to several pesticide applications in one vegetation season, the pesticide may be present in mixtures with other pesticides or xenobiotics in soil. This study examines the role which a mixture of chemicals plays in pesticide degradation. The influence of other pesticides on the rate of pendimethalin (PDM) degradation in soil was measured in controlled conditions. Mixtures of PDM with mancozeb or mancozeb and thiamethoxam significantly influenced the degradation of pendimethalin under controlled conditions. The second type of mixtures, with metribuzin or thiamethoxam, did not affect the behavior of pendimethalin in soil. Also, we determined the influence of water content on the rate of pendimethalin degradation alone in two soils and compared it to the rate in three pesticide mixtures. We compared two equations to evaluate the predictors of the rate of herbicide dissipation in soil: the first-order kinetic and the non-linear empirical models. We used the non-linear empirical model assuming that the degradation rate of a herbicide in soil is proportional to the difference of the observed concentration of herbicide in soil at time and concentration of herbicide in the last day of measurement.

Topics: Aniline Compounds; Drug Interactions; Fungicides, Industrial; Herbicides; Insecticides; Kinetics; Maneb; Models, Chemical; Neonicotinoids; Nitro Compounds; Oxazines; Soil; Soil Pollutants; Thiamethoxam; Thiazoles; Zineb

The effect of selected pesticides, monocrotophos, chlorpyrifos alone and in combination with mancozeb and carbendazim, respectively, was tested on nitrification and phosphatase activity in two groundnut (Arachis hypogeae L.) soils. The oxidation of ammonical nitrogen was significantly enhanced under the impact of selected pesticides alone and in combinations at 2.5 kg ha(-1) in black soil, and furthermore, increase in concentration of pesticides decreased the rate of nitrification, whereas in the case of red soil, the nitrification was increased up to 5.0 kg ha(-1) after 4 weeks, and then decline phase was started gradually from 6 to 8 weeks of incubation. The activity of phosphatase was increased in soils, which received the monocrotophos alone and in combination with mancozeb up to 2.5 and 5.0 kg ha(-1), whereas the application of chlorpyrifos singly and in combination with carbendazim at 2.5 kg ha(-1) profoundly increased the phosphatase activity after 20 days of incubation, in both soils. But higher concentrations of pesticides were either innocuous or inhibitory to the phosphatase activity.

Topics: Arachis; Benzimidazoles; Carbamates; Fungicides, Industrial; India; Insecticides; Maneb; Nitrification; Organophosphorus Compounds; Phosphoric Monoester Hydrolases; Soil Microbiology; Zineb

Previous studies demonstrate a positive correlation between pesticide usage and Parkinson's disease (PD), which preferentially targets dopaminergic (DAergic) neurons. In order to examine the potential relationship between two common pesticides and specific neurodegeneration, we chronically (24 h) or acutely (30 min) exposed two Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC(25), LC(50) or LC(75)) of TouchDown(®) (TD) as percent active ingredient (glyphosate), or Mancozeb(®) (MZ) as percent active ingredient (manganese/zinc ethylene-bis-dithiocarbamate). Furthermore, to more precisely model environmental exposure, worms were also exposed to TD for 30 min, followed by 30-min incubation with varying MZ concentrations. Previous data from out lab suggested general neuronal degeneration using the worm strain NW1229 (pan-neuronal//green fluorescent protein (GFP) construct). To determine whether distinct neuronal groups were preferentially affected, we specifically used EG1285 (GABAergic neurons//GFP construct) and BZ555 (DAergic neurons//GFP construct) worms to verify GABAergic and DAergic neurodegeneration, respectively. Results indicated a statistically significant decrease, when compared to controls (CN), in number of green pixels associated with GABAergic neurons in both chronic (*P < 0.05) and acute (*P < 0.05) treatment paradigms. Analysis of the BZ555 worms indicated a statistically significant decrease (*P < 0.05) in number of green pixels associated with DAergic neurons in both treatment paradigms (chronic and acute) when compared to CN. Taken together, our data suggest that exposure to TD and/or MZ promotes neurodegeneration in both GABAergic and DAergic neurons in the model organism C. elegans.

Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Dopaminergic Neurons; Dose-Response Relationship, Drug; Drug Interactions; Fungicides, Industrial; GABAergic Neurons; Glycine; Glyphosate; Green Fluorescent Proteins; Interneurons; Maneb; Motor Neurons; Nerve Degeneration; Organophosphorus Compounds; Pesticides; Zineb

The kinetic and thermodynamic parameters of mancozeb degradation in tomato homogenates under the conditions prevailing in the manufacture of tomato products (at 60-100 °C for 0-60 min) were investigated. A gas chromatography-mass spectrometry method was used to analyse residual mancozeb in tomato homogenate. Ethylenethiourea (ETU), the main toxic degradation product of mancozeb, was measured by high-performance liquid chromatography (HPLC)-with photodiode array detector (PDA).. The degradation of mancozeb and the formation of ETU in tomato homogenates were adequately described as first-order kinetics. Dependence of the rate constant followed the Arrhenius relationship. Apparent activation energies, temperature coefficients, half time and time to reduce to 90% of the initial value of mancozeb were calculated as kinetic parameters. The thermodynamic parameters of mancozeb were also described as Δg(d) = - 2.440 and 7.074 kJ mol⁻¹; Δh(d) = - 32.555 and - 42.767 kJ mol⁻¹; Δs(d) = - 0.090 and - 0.150 kJ mol⁻¹ K⁻¹; K(e) = 0.414 and 9.797 L g⁻¹ for 333 and 373 K respectively.. Current findings may shed light on the reduction of mancozeb residue and its toxic degradation product during thermal processing of tomatoes and may also be valuable in awareness and prevention of potential risks from dietary exposure.

Topics: Carcinogens; Chromatography, High Pressure Liquid; Cooking; Drug Stability; Ethylenethiourea; Food Contamination; Food Preservation; Fruit; Fungicides, Industrial; Half-Life; Hot Temperature; Kinetics; Maneb; Pesticide Residues; Photometry; Solanum lycopersicum; Spectrophotometry, Ultraviolet; Thermodynamics; Turkey; Zineb

Mancozeb is a dithiocarbamate fungicide known to be genotoxic and induces tumors in rodents at various sites. There is no report in the literature about its genotoxicity in humans. Here, we investigated the association between mancozeb exposure and induction of genotoxic and proapoptotic changes in cultured human lymphocytes (CHLs).. Lymphocytes were isolated from peripheral blood of healthy non-smoking donors. Induction of micronuclei and chromosomal aberrations was recorded both by conventional and flow cytometric methods. Annexin-V FITC was used for the differentiation of apoptotic and necrotic cells by flow cytometry.. Mancozeb exposure (0.5, 2 and 5 μg/ml) to CHLs leads to significant induction in the frequency of chromosomal aberrations (CAs) and micronuclei (MN), in a dose-dependent manner. Concomitantly, pro-oxidant potential of mancozeb was also recorded, by increase in the levels of reactive oxygen species (ROS) generation. Our results demonstrated that ROS plays a critical role in the initiation of mancozeb induced apoptosis in CHLs through two ways, primarily through mitochondria-mediated pathway including induction of ROS, decrease in mitochondrial membrane potential (ΔΨm), along with cytochrome c release from mitochondria, and activation of the caspase cascade. The other pathway includes increase in ROS, which resulted in activation of NF-κB, expression of FasL and triggered FasL-dependent pathway, which also involves caspase-8. Therefore, exposure to mancozeb can lead to induction of apoptosis in CHLs through both mechanisms.. The results of study confirm that mancozeb exposure can induce genotoxicity and apoptosis in CHLs, thus pose a potential risk to exposed human population.

Topics: Annexin A5; Apoptosis; Cells, Cultured; Chromosome Aberrations; Cytochromes c; Dose-Response Relationship, Drug; Flow Cytometry; Fluorescein-5-isothiocyanate; Fungicides, Industrial; Humans; Lymphocytes; Maneb; Membrane Potential, Mitochondrial; Micronuclei, Chromosome-Defective; Mitochondria; Mutagenicity Tests; Reactive Oxygen Species; Zineb

Residue dynamics of fenamidone and mancozeb on gherkin was evaluated at two different agro climatic zones i.e. at Bangalore (Zone-1) and Dharwad (Zone-2) in the state of Karnataka, India. Two treatments of the combination formulation (fenamidone 10% + mancozeb 50%) were given at the standard dose 150 + 750 g a.i. ha(-1) and double dose 300 + 1,500 g a.i. ha(-1). Initial residue deposits of fenamidone were 0.467 and 0.474 mg kg(-1) at Zone-1 and 2, respectively from standard dose treatment. From double dose treatment they were 0.964 and 0.856 mg kg(-1), respectively. Fenamidone residues persisted for 15 and 10 days and dissipated with the half-life of 4 and 3 days at Zone-1 and 2, respectively. Mancozeb residue deposits on gherkin were 0.383 and 0.428 mg kg(-1) from standard dose and 0.727 and 0.626 mg kg(-1) from double dose treatment at Zone-1 and 2, respectively. Mancozeb residues dissipated with the half-life of 2 and 1 day, respectively. Residues of both fenamidone and mancozeb dissipated faster at Zone-2 compared to Zone-1. The limit of quantification of fenamidone and mancozeb were 0.02 and 0.1 mg kg(-1), respectively in both gherkin and soil. Residues of fenamidone and mancozeb in soil collected on the 20th day from the 2 locations were found to be below quantifiable limit of both fungicides.

Topics: Climate; Cucumis sativus; Environmental Monitoring; Fungicides, Industrial; Imidazolines; India; Maneb; Pesticide Residues; Strobilurins; Zineb

The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant.

Topics: Animals; Apoptosis; Blotting, Western; Cell Proliferation; Female; Fungicides, Industrial; Granulosa Cells; Humans; Maneb; Mice; Microscopy, Confocal; Ovarian Follicle; Tumor Suppressor Protein p53; Zineb

A study of the in vitro sensitivity of 12 isolates of Phytophthora infestans to metalaxyl, azoxystrobin, dimethomorph, cymoxanil, zoxamide and mancozeb, was conducted. The isolates derived from infected potato leaves collected at eight different localities in Serbia during 2005-2007. The widest range of EC(50) values for mycelial growth of the isolates was recorded for metalaxyl. They varied from 0.3 to 3.9 μg mL(-1) and were higher than those expected in a susceptible population of P. infestans. The EC(50) values of the isolates were 0.16-0.30 μg mL(-1) for dimethomorph, 0.27-0.57 μg mL(-1) for cymoxanil, 0.0026-0.0049 μg mL(-1) for zoxamide and 2.9-5.0 μg mL(-1) for mancozeb. The results indicated that according to effective concentration (EC(50)) the 12 isolates of P. infestans were sensitive to azoxystrobin (0.019-0.074 μg mL(-1)), and intermediate resistant to metalaxyl, dimethomorph and cymoxanil. According to resistance factor, all P. infestans isolates were sensitive to dimethomorph, cymoxanil, mancozeb and zoxamide, 58.3% of isolates were sensitive to azoxystrobin and 50% to metalaxyl. Gout's scale indicated that 41.7% isolates were moderately sensitive to azoxystrobin and 50% to metalaxyl.

Topics: Acetamides; Alanine; Amides; Maneb; Methacrylates; Morpholines; Pesticides; Phytophthora infestans; Plant Diseases; Pyrimidines; Serbia; Solanum tuberosum; Strobilurins; Zineb

The persistence of fungicides on two commercial cultivars of potato was determined under field conditions at Punjab Agricultural University, Ludhiana, Punjab. Initial deposits of mancozeb on potato leaves were found to be 26.9 and 38.7 mg kg(-1), following application of ready mixture of fungicide metalaxyl 8% + mancozeb 64% (Ridomil MZ) at the rate of 1260 and 2520 g a.i. ha(-1), whereas metalaxyl residues were found to be 35.1 and 49.5 mg kg(-1), respectively. The residue level of mancozeb in potato leaves 15 days after application at single and double doze were 19.0 and 27.0 mg kg(-1) showing a loss of 29.6 and 30.3%, whereas the values for metalaxyl at single and double doze were 0.40 and 0.80 mg kg(-1) showing a loss of 98.9 and 98.4%, respectively. Residues of mancozeb and metalaxyl were not detected at 0.04 and 0.02 mg kg(-1) level in potato tubers at harvest (PHI = 53 days) at both the dosages, respectively. The persistence and dissipation of mancozeb with the application of Ridomil MZ followed similar trend as in Indofil M-45. The rate of fungicide dissipation increased with time after application in both the potato cultivars 'Kufri Chandramukhi' and 'Chipsona'. No significant difference was observed on initial deposit, persistence and dissipation of the two molecules between the two potato cultivars.

Topics: Alanine; Fungicides, Industrial; Humans; Maneb; Pesticide Residues; Plant Diseases; Plant Leaves; Soil Pollutants; Solanum tuberosum; Zineb

There is growing concern of permanent damage to the endocrine and nervous systems after developmental exposure to endocrine disrupting chemicals. In this study the permanent reproductive and neurobehavioral effects of combined exposure to five endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, were examined. Pregnant and lactating rat dams were dosed with a mixture of the five pesticides at three different doses, or with the individual pesticides at one of two doses. Adverse effects were observed in young and adult male offspring from the group exposed to the highest dose of the mixture. These included reduced prostate and epididymis weights, increased testes weights, altered prostate histopathology, increased density of mammary glands, reduced sperm counts, and decreased spatial learning. As no significant effects were seen following single compound exposure at the doses included in the highest mixture dose, these results indicate cumulative adverse effects of the pesticide mixture.

Topics: Animals; Behavior, Animal; Bridged Bicyclo Compounds; Drug Interactions; Endocrine Disruptors; Epoxy Compounds; Female; Genitalia, Male; Imidazoles; Learning; Male; Mammary Glands, Animal; Maneb; Memory; Organ Size; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sperm Count; Triazoles; Zineb

The effects of the fungicides Maneb, Mancozeb, and Zineb were investigated in transformed colon cells, HT-29, Caco2 and non-transformed cells, CCD-18Co. Significant decreases in viability were observed with Maneb and Mancozeb in HT-29 and CCD-18Co (80-260μM), and Caco2 cells (40-180μM). No significant decreases in viability were observed in all cell types up to 800μM with Zineb. MnCl(2) and ZnCl(2) exposure produced no loss of viability in all cell types up to 400μM. Light microscopy confirmed viability analysis. Lipid peroxidation was observed with Maneb and Mancozeb in cell types tested (60-200μM). Caspase 3/7, 8, and 9 activities were observed with Maneb and Mancozeb in cell types tested (40-200μM). Maneb and Mancozeb treated HT-29 and Caco2 cells demonstrated increases in manganese and zinc concentrations (20-200μM). The lack of toxicity observed with Zineb, MnCl(2), and ZnCl(2) suggests that both the metal moiety and the organic portion of these fungicides together contribute to toxicity.

Topics: Caco-2 Cells; Caspases; Cell Line; Cell Survival; Chlorides; Fungicides, Industrial; HT29 Cells; Humans; Lipid Peroxidation; Maneb; Manganese; Manganese Compounds; Zinc; Zinc Compounds; Zineb

Intensive use of pesticides, particularly dithiocarbamates, in agriculture often leads to contamination of freshwater ecosystems. To our knowledge, the mechanisms of toxicity to fish by the carbamate fungicide Tattoo that contains mancozeb [ethylenebis(dithiocarbamate)] have not been studied. The present study aimed to evaluate the effects of Tattoo on goldfish gills and blood, tissues that would have close early contact with the pollutant. Exposure of goldfish Carassius auratus to 3, 5 or 10mgL(-1) of Tattoo for 96h resulted in moderate lymphopenia (by 8 percent) with a concomitant increase in both stab (by 66-88 percent) and segmented (by 166 percent) neutrophils. An increase in the content of protein carbonyl groups in blood (by 137-184 percent) together with decreased levels of protein thiols (by 23 percent) and an enhancement of lipid peroxide concentrations (by 29 percent) in gills after exposure to 10mgL(-1) of Tattoo demonstrated the induction of mild oxidative stress in response to Tattoo exposure. At the same time, the activities of selected antioxidant enzymes were enhanced in gills: superoxide dismutase by 18-25 percent and catalase by 27 percent. A 34 percent increment in low molecular mass thiol concentrations (mainly represented by glutathione) also occurred in gills and could be related to increased activity (by 13-30 percent) of glucose-6-phosphate dehydrogenase. The results indicate that Tattoo exposure perturbs free radical processes, i.e. induces mild oxidative stress and enhances the activity of certain antioxidant and associated enzymes in goldfish gills. It is clear that goldfish respond to the presence of waterborne pesticide by adjusting antioxidant defenses through upregulation of activities of antioxidant and associated enzymes.

Topics: Animals; Antioxidants; Catalase; Fungicides, Industrial; Gills; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Goldfish; Lipid Peroxides; Lymphopenia; Maneb; Oxidative Stress; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Water Pollutants, Chemical; Zineb

Benalaxyl-M [methyl N-phenylacetyl-N-2, 6-xylyl-DL-alaninate] is a newly introduced phenyl-amide fungicide whereas Mancozeb is one of the member of ethylenebisdiothiocarbamate (EBDC) fungicide. Benalaxyl-M in combination with Mancozeb effectively controls downy mildew of grapes. A two season field trial was conducted under West Bengal climatic condition during 2009-2010 to evaluate the dissipation pattern of fungicide mixture (Benalaxyl-M 4 % + Mancozeb 65 %) WP in grapes at two application rates (2,750 g and 5,500 g ha(-1)). The quantitative analysis was performed using liquid chromatography-mass spectrometry (LC-MS/MS) and UV-Vis spectrophotometer for Benalaxyl-M and Mancozeb residues respectively. Following the first order kinetics the fungicide Benalaxyl-M dissipates in grapes with half-life (T(1/2)) value ranges between 2.59 and 2.79 days irrespective of seasons and doses. The dissipation pattern of Mancozeb also follows first order kinetics with half-life (T(1/2)) value ranges between 3.86 and 4.93 days irrespective of seasons and doses.

Topics: Alanine; Food Contamination; Fungicides, Industrial; Half-Life; Kinetics; Maneb; Models, Chemical; Pesticide Residues; Risk Assessment; Vitis; Zineb

Topics: Fungicides, Industrial; Humans; Male; Maneb; Middle Aged; Parkinsonian Disorders; Zineb

A 56.56-kDa extracellular chitinase from Paenibacillus sp. D1 was purified to 52.3-fold by ion exchange chromatography using SP Sepharose. Maximum enzyme activity was recorded at pH 5.0 and 50 °C. MALDI-LC-MS/MS analysis identified the purified enzyme as chitinase with 60% similarity to chitinase Chi55 of Paenibacillus ehimensis. The activation energy (E (a)) for chitin hydrolysis and temperature quotient (Q (10)) at optimum temperature was found to be 19.14 kJ/mol and 1.25, respectively. Determination of kinetic constants k (m), V (max), k (cat), and k (cat)/k (m) and thermodynamic parameters ΔH*, ΔS*, ΔG*, ΔG*(E-S), and ΔG*(E-T) revealed high affinity of the enzyme for chitin. The enzyme exhibited higher stability in presence of commonly used protectant fungicides Captan, Carbendazim, and Mancozeb compared to control as reflected from the t (1/2) values suggesting its applicability in integrated pest management for control of soil-borne fungal phytopathogens. The order of stability of chitinase in presence of fungicides at 80 °C as revealed from t (1/2) values and thermodynamic parameters E (a(d)) (activation energy for irreversible deactivation), ΔH*, ΔG*, and ΔS* was: Captan > Carbendazim > Mancozeb > control. The present study is the first report on thermodynamic and kinetic characterization of chitinase from Paenibacillus sp. D1.

Topics: Bacterial Proteins; Benzimidazoles; Captan; Carbamates; Chitin; Chitinases; Chromatography, Ion Exchange; Enzyme Stability; Fungi; Fungicides, Industrial; Half-Life; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Maneb; Paenibacillus; Pest Control; Temperature; Thermodynamics; Zineb

The widely used fungicide mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100, or 150 mg mancozeb/kg body weight (bw)/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T(4)) levels were measured in dams during gestation. On PND 16, hormone levels and several organ weights were measured in the offspring, whereas motor activity, startle response, and cognitive function were assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams and was therefore reduced to 100 mg/kg bw/day in mid study. T(4) levels showed a dose-dependent and significant decrease in dams from all three dose groups on GD 15, whereas offspring T(4) levels, thyroid weights, and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did, however, reduce T(4) levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affects the developing brain.

Topics: Animals; Behavior, Animal; Dose-Response Relationship, Drug; Endocrine Disruptors; Female; Fungicides, Industrial; Gestational Age; Male; Maneb; Maternal Exposure; Pregnancy; Rats; Rats, Wistar; Thyroid Hormones; Zineb

A methodology based on the vapour phase (VP) generation of carbon disulphide from non-volatile dithiocarbamate compounds has been developed for determination of pesticide residues in foodstuff at low ppm levels. The method involves a selective reaction combined with liquid phase microextraction (LPME) and transmission infrared measurements. The use of a home made transmission cell improved the detection limits (LOD) compared to the use of attenuated total reflectance measurements by a factor of approximately 80. Using the most appropriate experimental conditions for the CS(2) generation and LPME preconcentration, the precision of the methodology, expressed as the relative standard deviation (RSD), was of the order of 3.1% and the absolute LOD was 0.3 μg dithiocarbamate, which corresponds to 60-120 μg kg(-1), for a sample mass ranging from 2.5 to 5 g. The usefulness of the methodology has been evidenced by the determination of mancozeb residues in strawberries, lettuce and corn samples at concentrations between 1 and 5 mg kg(-1), where the VP-LPME IR provided results comparable with those obtained by a head space gas chromatography mass spectrometry reference procedure.

Topics: Chemical Fractionation; Ethylenebis(dithiocarbamates); Food Analysis; Gas Chromatography-Mass Spectrometry; Limit of Detection; Maneb; Pesticide Residues; Spectrophotometry, Infrared; Zineb

Mancozeb, ethylene(bis)dithiocarbamate fungicides, has been well documented in the literature as a multipotent carcinogen, but the underlying mechanism remains unrevealed. Thus, mancozeb has been selected in this study with the objective to decipher the molecular mechanism that culminates in carcinogenesis. We employed two-dimensional gel electrophoresis and mass spectrometry to generate a comparative proteome profile of control and mancozeb (200 mg/kg body weight) exposed mouse skin. Although many differentially expressed proteins were found, among them, two significantly upregulated proteins, namely, S100A6 (Calcyclin) and S100A9 (Calgranulin-B), are known markers of keratinocyte differentiation and proliferation, which suggested their role in mancozeb-induced neoplastic alterations. Therefore, we verified these alterations in the human system by using HaCaT cells as an in vitro model for human skin keratinocyte carcinogenesis. Upregulation of these two proteins upon mancozeb (0.5 μg/mL) exposure in HaCaT cells indicated its neoplastic potential in human skin also. This potential was confirmed by increase in number of colonies in colony formation and anchorage-independent growth assays. Modulation of S100A6/S100A9 targets, elevated phosphorylation of extracellular signal regulated kinase (ERK1/2), Elk1, nuclear factor- kappa B and cell division cycle 25 C phosphatase, and cyclin D1 and cyclooxygenase-2 upregulation was seen. In addition, PD98059 (ERK1/2 inhibitor) reduced cell proliferation induced by mancozeb, confirming the involvement of ERK1/2 signaling. Conclusively, we herein present the first report asserting that the mechanism involving S100A6 and S100A9 regulated ERK1/2 signaling underlies the mancozeb-induced neoplastic potential in human skin.

Topics: Animals; Blotting, Western; Calgranulin B; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Fungicides, Industrial; Humans; Keratinocytes; Male; Maneb; Mice; Phosphorylation; S100 Calcium Binding Protein A6; S100 Proteins; Signal Transduction; Skin; Skin Neoplasms; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Zineb

Epidemiological evidence suggests positive correlations between pesticide usage and the incidence of Parkinson's disease (PD). To further explore this relationship, we used wild type (N2) Caenorhabditis elegans (C. elegans) to test the following hypothesis: Exposure to a glyphosate-containing herbicide (TD) and/or a manganese/zinc ethylene-bis-dithiocarbamate-containing fungicide (MZ) may lead to neurotoxicity. We exposed N2 worms to varying concentrations of TD or MZ for 30 min (acute) or 24h (chronic). To replicate agricultural usage, a third population was exposed to TD (acute) followed by MZ (acute). For acute TD exposure, the LC(50)=8.0% (r(2)=0.6890), while the chronic LC(50)=5.7% (r(2)=0.9433). Acute MZ exposure led to an LC(50)=0.22% (r(2)=0.5093), and chronic LC(50)=0.50% (r(2)=0.9733). The combined treatment for TD+MZ yielded an LC(50)=12.5% (r(2)=0.6367). Further studies in NW1229 worms, a pan-neuronally green fluorescent protein (GFP) tagged strain, indicated a statistically significant (p<0.05) and dose-dependent reduction in green pixel number in neurons of treated worms following each paradigm. This reduction of pixel number was accompanied by visual neurodegeneration in photomicrographs. For the dual treatment, Bliss analysis suggested synergistic interactions. Taken together, these data suggest neuronal degeneration occurs in C. elegans following treatment with environmentally relevant concentrations of TD or MZ.

Topics: Analysis of Variance; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Dose-Response Relationship, Drug; Drug Synergism; Fungicides, Industrial; Glycine; Glyphosate; Green Fluorescent Proteins; Herbicides; Lethal Dose 50; Maneb; Microscopy, Fluorescence; Nerve Degeneration; Neurons; Time Factors; Zineb

Earthworm avoidance behaviour test is an important screening tool in soil eco-toxicology. This test has been developed and validated under North American and European conditions. However, little research has been performed on the avoidance test in the tropics. This work demonstrates the potential suitability of the avoidance behaviour test as screening method in the highlands of Colombia using Eisenia fetida as the bio-indicator species on contaminated soils with carbofuran and chlorpyrifos. Though for the two active ingredients 100% avoidance was not reached, a curve with six meaningful concentrations is provided. No significant avoidance behaviour trend was found for mancozeb and methamidophos. Tests were conducted in the field yielded similar results to the tests carried out in the laboratory for chlorpyrifos and mancozeb. However, for the case of carbofuran and methamidophos, differences of more than double in avoidance were obtained. Divergence might be explained by soil and temperature conditions.

Topics: Animals; Avoidance Learning; Carbofuran; Chlorpyrifos; Colombia; Dose-Response Relationship, Drug; Environmental Monitoring; Fungicides, Industrial; Insecticides; Maneb; Oligochaeta; Organothiophosphorus Compounds; Soil; Soil Pollutants; Zineb

The aim of this study is to investigate the effects of the pesticides/polycyclic aromatic hydrocarbon mixture on aryl hydrocarbon receptor (AhR), p53 and ubiquitin mRNA level in haemocytes of Mya arenaria exposed to a mixture of chlorothalonil, mancozeb and benzo[a]pyrene (BaP) for 48 and 72 h. AhR, p53 and ubiquitin gene expression levels were quantified using quantitative Real-time PCR. For robust and accurate quantification of transcripts, suitable housekeeping genes were selected from four sets of ribosomal and elongation factors transcripts previously sequenced from Mya arenaria using geNorm open source software. Quantitative Real-time PCR data exhibited a significantly high expression of AhR after 72 h of exposure (P ≤ 0.05). p53 gene expression seems to be up-regulated by the mixture after 48 h, however not significantly; but the level of p53 mRNA is down-regulated by the xenobiotics between 48 and 72 h after exposure. This study postulates that AhR mRNA levels could be used as an indicator of the exposure of clams' haemocytes to a mixture of xenobiotics such as chlorothalonil, mancozeb and BaP. However, further studies have to be pursued in order to unravel the molecular mechanisms involved in the p53 signaling pathway.

Topics: Animals; Benzo(a)pyrene; Biomarkers; Gene Expression Regulation; Genes, p53; Hemocytes; Maneb; Mya; Nitriles; Pesticides; Real-Time Polymerase Chain Reaction; Receptors, Aryl Hydrocarbon; Ubiquitin; Water Pollutants, Chemical; Xenobiotics; Zineb

In this study we address the problem of finding a quantitative mathematical model for the genetic network regulating the stress response of the yeast Saccharomyces cerevisiae to the agricultural fungicide mancozeb. An S-system formalism was used to model the interactions of a five-gene network encoding four transcription factors (Yap1, Yrr1, Rpn4 and Pdr3) regulating the transcriptional activation of the FLR1 gene. Parameter estimation was accomplished by decoupling the resulting system of nonlinear ordinary differential equations into a larger nonlinear algebraic system, and using the Levenberg-Marquardt algorithm to fit the models predictions to experimental data. The introduction of constraints in the model, related to the putative topology of the network, was explored. The results show that forcing the network connectivity to adhere to this topology did not lead to better results than the ones obtained using an unrestricted network topology. Overall, the modeling approach obtained partial success when trained on the nonmutant datasets, although further work is required if one wishes to obtain more accurate prediction of the time courses.

Topics: Computational Biology; DNA-Binding Proteins; Fungicides, Industrial; Gene Regulatory Networks; Genes, Fungal; Maneb; Models, Genetic; Nonlinear Dynamics; Organic Anion Transporters; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Stress, Physiological; Transcription Factors; Transcriptional Activation; Zineb

Qualitative models allow understanding the relation between the structure and the dynamics of gene regulatory networks. The dynamical properties of these models can be automatically analysed by means of formal verification methods, like model checking. This facilitates the model-validation process and the test of new hypotheses to reconcile model predictions with the experimental data.. The authors report in this study the qualitative modelling and simulation of the transcriptional regulatory network controlling the response of the model eukaryote Saccharomyces cerevisiae to the agricultural fungicide mancozeb. The model allowed the analysis of the regulation level and activity of the components of the gene mancozeb-induced network controlling the transcriptional activation of the FLR1 gene, which is proposed to confer multidrug resistance through its putative role as a drug eflux pump. Formal verification analysis of the network allowed us to confront model predictions with the experimental data and to assess the model robustness to parameter ordering and gene deletion.. This analysis enabled us to better understand the mechanisms regulating the FLR1 gene mancozeb response and confirmed the need of a new transcription factor for the full transcriptional activation of YAP1. The result is a computable model of the FLR1 gene response to mancozeb, permitting a quick and cost-effective test of hypotheses prior to experimental validation.

Topics: Algorithms; Computational Biology; Computer Simulation; Fungicides, Industrial; Gene Expression Regulation, Fungal; Gene Regulatory Networks; Maneb; Models, Biological; Models, Statistical; Models, Theoretical; Organic Anion Transporters; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Systems Biology; Transcription Factors; Transcriptional Activation; Zineb

Field tests are useful for the evaluation of the pesticides' impact in realistic use situations. However, the distinction between the direct and indirect effects of a pesticide is not always possible in field, with consequences on the conclusions about pesticides toxicity. Generalist predatory mites belonging to the Phytoseiidae family are widely considered as non-target organisms in pesticide side-effect evaluations. Plant pathogens of several cultivated plants can be of importance as food resources for various phytoseiids. Pesticides with fungicidal activity may have a direct impact on phytoseiids, but they can also have an indirect effect reducing food availability for predatory mites. Here, we present the results of field experiments performed on grapevine, where we investigate whether the availability of the plant pathogen grape downy mildew has an effect on fungicides impact on the predatory mites Typhlodromus pyri Scheuten and Amblyseius andersoni (Chant). In these experiments we used fungicides characterized by differential selectivity to predatory mites in laboratory: copper compounds, folpet, and mancozeb. Results indicated that the abundance of predatory mites was associated with the plant pathogen foliar symptoms presence. The presence of predatory mites was different among treatments in response of the toxicological traits of a pesticide (direct effects), but also as consequences of differential plant pathogen availability induced by fungicide applications (indirect effects). During the investigation, the variable plant pathogen spread on untreated control determined contrasting results on pesticides effect. We segregated the direct effects from the indirect food resource-mediated effects including a non-toxic reference in the experimental protocols.

Topics: Animals; Environmental Monitoring; Environmental Pollutants; Fungicides, Industrial; Maneb; Mites; Predatory Behavior; Vitis; Zineb

Abstract Saccharomyces cerevisiae was used to uncover the mechanisms underlying tolerance and toxicity of the agricultural fungicide mancozeb, linked to cancer and Parkinson's disease development. Chemogenomics screening of a yeast deletion mutant collection revealed 286 genes that provide protection against mancozeb toxicity. The most significant Gene Ontology (GO) terms enriched in this dataset are associated to transcriptional machinery, vacuolar organization and biogenesis, intracellular trafficking, and cellular pH regulation. Clustering based on physical and genetic interactions further highlighted the role of oxidative stress response, protein degradation and carbohydrate/energy metabolism in mancozeb stress tolerance. Mancozeb was found to act in yeast as a thiol-reactive compound, but not as a free radical or reative oxygen species (ROS) inducer, leading to massive oxidation of protein cysteins, consistent with the requirement of genes involved in glutathione biosynthesis and reduction and in protein degradation to provide mancozeb resistance. The identification of Botrytis cinerea homologues of yeast mancozeb tolerance determinants is expected to guide studies on mancozeb mechanisms of action and tolerance in phytopathogenic fungi. The generated networks of protein-protein associations of yeast mancozeb tolerance determinants and their human orthologues share a high degree of similarity. This toxicogenomics analysis may, thus, increase the understanding of mancozeb toxicity and adaptation mechanisms in humans.

Topics: Drug Resistance, Fungal; Electron Spin Resonance Spectroscopy; Fungicides, Industrial; Gene Expression Regulation, Fungal; Genome, Fungal; Humans; Maneb; Protein Carbonylation; Reactive Oxygen Species; Saccharomyces cerevisiae; Sulfhydryl Compounds; Zineb

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range-finding mixture studies, rats were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual differentiation of the pups was affected at 25% and higher as anogenital distance was affected in both male and female offspring at birth and the male offspring exhibited malformations of the genital tubercle, increased nipple retention, and decreased prostate and epididymis weights at pup day 13. The results show that doses of endocrine disrupting pesticides, which appear to induce no effects on gestation length, parturition and pup mortality when judged on their own, induced marked adverse effects on these endpoints in concert with other pesticides. In addition, the sexual differentiation of the offspring was affected. This as well as the predictability of the combination effects based on dose-additivity modelling will be studied further in a large dose-response study.

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Bridged Bicyclo Compounds; Endocrine Disruptors; Epoxy Compounds; Female; Fungicides, Industrial; Imidazoles; Litter Size; Male; Maneb; Maternal Exposure; Mortality; No-Observed-Adverse-Effect Level; Parturition; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Sex Differentiation; Triazoles; Zineb

The effects of abundant Mancozeb (Mn, Zn-bisdithiocarbamate) applications (2.5 kg ha⁻¹week⁻¹ for 10 years) on soil and surface-, subsurface- and groundwater pollution were monitored in a banana production region of tropical Mexico. In soils, severe manganese accumulation was observed, wheras the main metabolite ethylenethiourea was near the detection limit. Surface and subsurface water was highly polluted with ethylenethiourea, the main metabolite of Mancozeb (22.5 and 4.3 μg L⁻¹, respectively), but not with manganese. In deep ground water, no ethylenethiourea was detected. The level of pollution in the region presents a worrisome risk for aquatic life and for human health.

Topics: Environmental Monitoring; Environmental Pollutants; Food Handling; Fresh Water; Fungicides, Industrial; Maneb; Manganese; Mexico; Musa; Soil; Tropical Climate; Zinc; Zineb

Thermal decomposition under both air and inert atmospheres of a commercial Mancozeb product was investigated through thermogravimetric analysis and laboratory scale thermal treatment from 20°C to 950°C, with analysis of gaseous and solid products. The aim of this study is the understanding of the thermal degradation mechanisms of a pesticide under different atmospheres and the chemical identification of the solid and gaseous pollutants which can be emitted during warehouse fires and which can constitute a threat for health and environment. Pyrolysis of Mancozeb takes place between 20°C and 950°C and lead essentially to CS(2) and H(2)S emissions with formation at 950°C of MnS and ZnS. Thermal oxidation of Mancozeb under air occurs between 150°C and 950°C with formation of CO, CO(2) and sulphur gases (CS(2) and SO(2)). The first step (155-226°C) is the loss of CS(2) and the formation of ethylene thiourea, ZnS and MnS. The metallic sulphides are oxidized in ZnO and MnSO(4) between 226°C and 650°C (steps 2 and 3). MnSO(4) is then oxidized in Mn(3)O(4) during the last step (step 4) between 650°C and 950°C. At 950°C, carbon recovery is close to 95%. Sulphur recovery is close to 98% with an equal partition between SO(2) and CS(2).

Topics: Hot Temperature; Maneb; Microscopy, Electron, Transmission; Pesticides; Thermogravimetry; Zineb

Saccharomyces cerevisiae as model system was used to evaluate the occurrence of resistant mutants and adaptation mechanism to mancozeb (MZ), a widespread fungicide of the dithiocarbamate class with a broad spectrum of action and multiple cell targets. We were unable to isolate mutants resistant to inhibitory concentration of MZ but found an unusually large number of mitochondrial defective petite mutants among cells incubated in the presence of subinhibitory MZ concentration. Similar results were obtained with two other dithiocarbamate fungicides. Comparison of wild type and petite mutants showed that the latter were more resistant to toxic effects of MZ, highlighting the role of mitochondria in MZ-tolerance. The data suggest that petite cells, arising by exposure to sub-inhibitory MZ concentration, are not induced by fungicides but are spontaneous mutants already present in the population before the contact with the fungicide.

Topics: Drug Resistance, Fungal; Drug Tolerance; Fungicides, Industrial; Maneb; Mitochondria; Mutation; Saccharomyces cerevisiae; Thiocarbamates; Zineb

A gas chromatographic method with flame photometric detection (FPD (sulfur filter)) for analyzing the residues of 4 dithiocarbamates in 22 matrices in a heated closed vial has been established. The dithiocarbamate residues were decomposed to carbon disulfide (CS2) by SnCl2-HCl solution. The liberated CS2 was absorbed by hexane in the vial, and then determined by gas chromatography with FPD (sulfur filter). The results were expressed as the residues of dithiocabamates. The residue analysis method was validated by mancozeb, metiram, propineb and thiram in 22 matrices (apple, grape, etc). The average recovery ranges were from 72% to 110% with the relative standard deviations (RSD) between 0.8% and 22.0% when the fortified concentrations were between 0.06 and 3.0 mg/kg, and the quantitative analysis was performed by using external standard method. The limits of detection were in the range of 0.01-0.1 mg/kg (S/N = 3), and the limits of quantification were between 0.02 and 0.2 mg/kg (S/N = 10) for the 4 dithiocarbamate residues in the 22 matrices. This method is simple, fast, accurate, reproducible, and suitable for the determination of the 4 dithiocarbamate residues in the matrices mentioned in this paper.

Topics: Chromatography, Gas; Ditiocarb; Food Contamination; Fruit; Fungicides, Industrial; Maneb; Pesticide Residues; Thiocarbamates; Vegetables; Zineb

In our study, effects of fungicides mancozeb and dinocap on C and N mineralization were measured in arable and grassland soil. The soils were treated with these fungicides at the application and 10 times lower doses and then incubated at 20 degrees C for 2 weeks. Carbon mineralization (basal and substrate-induced respiration) and nitrogen mineralization (potential ammonification and nitrification) were evaluated 1 and 14 days after the treatment. After 14 days, ammonification was decreased to 48% and 83% at dinocap application dose in arable and grassland soil, respectively. Application dose of mancozeb caused significant decrease of nitrification to 11.2% and 5.6% in arable and grassland soil, respectively. Basal respiration and substrate-induced growth were rather stimulated by fungicides, especially at lower application doses. To conclude, potential risk may exist to soil microorganisms and their activities in soils treated routinely by mancozeb or dinocap.

Topics: Ammonia; Animals; Carbon; Czech Republic; Daphnia; Dinitrobenzenes; European Union; Fungicides, Industrial; Hydrogen-Ion Concentration; Maneb; Nitrogen; Poaceae; Soil; Soil Microbiology; Zineb

Toxicogenomics has the potential to elucidate gene-environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70-family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans.

Topics: Electrophoresis, Gel, Two-Dimensional; Fungicides, Industrial; Gene Expression Regulation, Fungal; Maneb; Proteomics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Toxicology; Zineb

The aetiology of haemic neoplasia (HN) is unknown, so far but many causative factors are suggested such as viral, pollution and genetics. The aim of this study was to determine if, under chronic exposure, two major pesticides (chlorothalonil and mancozeb) which are used in potato production could induce HN in soft-shell clams (Mya arenaria). Short-term experiments with acute exposure were also performed. Clams were collected from an epizootic site (North River, PEI) and from a site free of the disease (Magdalen Islands, Quebec). The tetraploid level of haemocytes was assessed by flow cytometry for each clam to determine the HN status. The bioaccumulation of pesticides in tissues was quantified by gas chromatography/mass spectrometry (GC/MS) for chlorothalonil while mancozeb and manganese were quantified by inductively coupled plasma-mass spectrometer (ICP/MS). Long term exposure to fungicide Bravo 500((R)) did not induce high tetraploid levels on negative calm from North River and the analysis of the digestive gland and the mantle did not reveal any detectable level of chlorothalonil. In the Manzate 200 DF((R)), some clams revealed high level of tetraploid cells but no difference were observed between the treatments and the control. The analysis of the digestive gland and the mantle for manganese did not highlight any significant difference in tissue concentration (p=0.05). For the acute exposure, chlorothalonil analysis showed that the active ingredient is distributed between four chlorinated compounds: 99.5% for chlorothalonil isomers, 0.4% for pentachlorothalonil and 0.1% for trichlorothalonil isomers. For a 72 h experiment, the accumulation was within 4h; the higher tissue concentration of chlorothalonil was 59.2 microg g(-1) in the mantle after 48 h, following by a decrease to an undetectable level at the end. For the manganese, the accumulation was detected after 4h; the higher tissue concentration was 48.8 microg g(-1) in the mantle after 24h and, over the following 48 h, the accumulation decreased until the end of the trial. Based on the data, the accumulation of these fungicides seems to be transitory. Chlorothalonil and mancozeb are both oxidative-stress promoters and could have induced cell dysfunction while in the tissue. Study on the effect of these fungicides on the p53 protein system is an example of strategy that would provide information on cellular events promoting neoplasia.

Topics: Animals; Environmental Exposure; Fungicides, Industrial; Hemocytes; Maneb; Mya; Nitriles; Water Pollutants, Chemical; Zineb

Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives 8(a-j) were prepared by the treatment of substituted benzhydryl chlorides with 4-(3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl chlorides in the presence of dry methylene dichloride and triethyl amine. The synthesized compounds were characterized by (1)H-NMR, IR, and elemental analysis. All the synthesized compounds were evaluated in vitro for their efficacy as antimicrobial agents by artificial inoculation technique against standard strains of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria solani and Fusarium solani of tomato plants. We have briefly investigated the structure-activity relation studies and reveal that the nature of substitutions on benzhydryl ring and sulfonamide ring influences the antibacterial activity. Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed significant potent antimicrobial activities compared to the standard drugs chloramphenicol, mancozeb.

Topics: Alternaria; Anti-Infective Agents; Chloramphenicol; Dose-Response Relationship, Drug; Fusarium; Magnetic Resonance Spectroscopy; Maneb; Molecular Structure; Pesticides; Piperidines; Ralstonia solanacearum; Solanum lycopersicum; Spectrophotometry, Infrared; Structure-Activity Relationship; Xanthomonas axonopodis; Zineb

The effects of the fungicides dodine, benomyl, thiabendazole, mancozeb, cupric sulfate, and copper oxychloride were examined in vitro upon germination and further development of Evlachovaea sp. and Tolypocladium cylindrosporum. Fungicidal activity depended on concentrations and varied among products, fungi and the strains tested. Depending on the fungicidal concentration, germination of conidia was induced but germlings produced neither mycelium nor new conidia. There was a good recovery of both Evlachovaea sp. and T. cylindrosporum from previously sterilized soils with fungicide-supplemented medium. Fungi were resistant to copper oxychloride up to 30 g/l, and this fungicide was found to have no utility for a selective medium. Minimal fungicide concentrations for successful isolations were 1 mg/l for benomyl, 200 mg/l for cupric sulfate, 50 mg/l for dodine, 100 mg/l for mancozeb, and 4 mg/l for thiabendazole. Thiabendazole, which is easy to obtain and can be used in low quantities, showed the greatest utility for a selective medium with these entomopathogenic fungi.

Topics: Ascomycota; Benomyl; Copper; Copper Sulfate; Fungicides, Industrial; Guanidines; Hypocreales; Maneb; Mycology; Soil Microbiology; Thiabendazole; Zineb

Aquatic pollution is an important factor implicated in global amphibian declines. Often amphibians are exposed to sublethal levels of agrochemicals continuously throughout their larval period either because of application regimes or persistence of the chemicals in the larvae's environment. Although most studies have examined the effects of one-time or short-term exposure to contaminants on amphibian larvae, few have investigated the implications of continuous exposure over a substantial interval during larval development. We examined the effects of continuous exposure to environmentally relevant concentrations of two common pesticides--endosulfan (0.2, 1, and 5 microg/L) and mancozeb (16, 80, and 400 microg/L)--on the growth and survival of leopard frog tadpoles. The concentrations used are comparable to those estimated to be found in waterbodies near agricultural fields. The exposure period was seven weeks. Mortality was recorded daily, and length was measured photographically once before and twice during the exposure period. Both chemicals greatly reduced survival at these concentrations. Hazard ratios were significantly positive for all treatments. Growth rates of tadpoles exposed to endosulfan were not significantly reduced, but exposure to all three levels of mancozeb resulted in reduced growth rates. These results underscore the importance of further investigation into the effects of endosulfan and mancozeb on environmental and wildlife health.

Topics: Animals; Endosulfan; Environmental Monitoring; Environmental Pollutants; Larva; Maneb; Pesticides; Rana pipiens; Toxicity Tests, Chronic; Zineb

Isolates of Cladobotryum dendroides from Serbian mushroom farms and Agaricus bisporus F56 were tested for sensitivity to selected fungicides in vitro. Chlorothalonil was the most toxic fungicide to C. dendroides isolates (EC(50) values were below 1.68 mg L(-1)). Trifloxystrobin and kresoxim-methyl were not effective in growth inhibition of C. dendroides isolates (EC(50) values exceeded 300 mg L(-1)). Metalaxyl-M+mancozeb was the most toxic fungicide to strain F56 of A. bisporus, and iprodione the least toxic. The fungicide selectivity indexes for both C. dendroides and A. bisporus indicated that iprodione, chlorothalonil, captan and metalaxyl-M+mancozeb had satisfactory selective fungitoxicity. Iprodione had the best selectivity to both the pathogen and the host, although inferior than prochloraz manganese and carbendazim, fungicides officially recommended for mushroom cultivation in European Union (EU) countries.

Topics: Acetates; Agaricus; Alanine; Aminoimidazole Carboxamide; Captan; Fungicides, Industrial; Hydantoins; Hypocreales; Imines; Lethal Dose 50; Maneb; Methacrylates; Nitriles; Phenylacetates; Serbia; Strobilurins; Zineb

Comparatively little quantitative information is available on both the spatial and temporal relationships that develop between airborne inoculum and disease intensity during the course of aerially spread epidemics. Botrytis leaf blight and Botrytis squamosa airborne inoculum were analyzed over space and time during 2 years (2002 and 2004) in a nonprotected experimental field, using a 6 x 8 lattice of quadrats of 10 x 10 m each. A similar experiment was conducted in 2004 and 2006 in a commercial field managed for Botrytis leaf blight using a 5 x 5 lattice of quadrats of 25 x 25 m each. Each quadrat was monitored weekly for lesion density (LD) and aerial conidium concentration (ACC). The adjustment of the Taylor's power law showed that heterogeneity in both LD and ACC generally increased with increasing mean. Unmanaged epidemics were characterized in either year, with aggregation indices derived from SADIE (Spatial Analysis by Distance Indices). For LD, the aggregation indices suggested a random pattern of disease early in the season, followed by an aggregated pattern in the second part of the epidemic. The index of aggregation for ACC in 2002 was significantly greater than 1 at only one date, while it was significantly greater than 1 at most sampling dates in 2004. In both years and for both variables, positive trends in partial autocorrelation were observed mainly for a spatial lag of 1. In 2002, the overall pattern of partial autocorrelations over sampling dates was similar for LD and ACC with no significant partial autocorrelation during the first part of the epidemic, followed by a period with significant positive autocorrelation, and again no autocorrelation on the last three sampling dates. In 2004, there was no significant positive autocorrelation for LD at most sampling dates while for ACC, there was a fluctuation between significant and non-significant positive correlation over sampling dates. There was a significant spatial correlation between ACC at given date (t(i)) and LD 1 week later (t(i + 1)) on most sampling dates in both 2002 and 2004 for the unmanaged and managed sites. It was concluded that LD and ACC were not aggregated in the early stage of epidemics, when both disease intensity and airborne conidia concentration were low. This was supported by the analysis of LD and ACC from a commercial field, where managed levels of disease were low, and where no aggregation of both variables was detected. It was further concluded that a reliable m

Topics: Botrytis; Demography; Fungicides, Industrial; Maneb; Onions; Plant Diseases; Time Factors; Zineb

In summer 2006, a root rot caused by Fusarium oxysporum was observed in commercial farms on common bean (Phaseolus vulgaris) on the cv Billò and Borlotto. A study was undertaken in order to evaluate the efficacy of different biological control agents applied as seed dressing. In the presence of a medium-high disease incidence, among the biocontrol agents tested, Trichoderma harzianum T 22, Bacillus subtilis QST 713, followed by Pseudomonas chlororaphis, provided generally the best control. Their efficacy was also consistent in the different trials. Also the mixture of T. harzianum + T. viride provide a good disease control. Streptomyces griseoviridis and the 3 strains of Fusarim oxysporum, although less effective, provided a partial control of the disease. The fungicide mancozeb provided only a partial disease control.

Topics: Antibiosis; Bacillus subtilis; Fungicides, Industrial; Fusarium; Maneb; Pest Control, Biological; Phaseolus; Plant Roots; Pseudomonas; Streptococcus; Trichoderma; Zineb

Two Large scale field studies have been conducted to the same design in commercial apple orchards in north and south France. Mancozeb (Dithane M-45) was applied at its post-annex I use rate of 1.6 kg a.i./ha on four occasions with a spray interval of 7 days. Reference treatments of a water treated control and toxic reference of dimethoate were also included. Studies were of randomized block design with 4 replicates (4 plots of 6 adjacent rows of 8 trees, on a surface of approximately 16 x 21 m) per treatment. Leaf and canopy dwelling arthropods were sampled before and at regular intervals after application until the end of the season. A diverse range of arthropod taxa was sampled, counted and identified which enabled for an evaluation of key taxa such as predatory mites and other beneficials but also of the whole foliar dwelling arthropod community. This two level analysis allows for a thorough investigation of both direct and indirect effects of the test item on beneficial, pest and non-target arthropods and for a state of the art evaluation at the ecological community Level using ordination techniques. The findings from the two locations were highly consistent in that mancozeb applied four times at 1.6 g a.i./ha with a 7 day spray interval caused significant but short lived reductions in predatory Phytoseiid mites of >50% with rapid recovery approximately one month after application. These transient effects did not impact secondary pests such as rust mites (Eriophyoidea) and broad mites (Tarsonemidae). A wide range of arthropod taxa were investigated (229 taxa in the north and 215 taxa in the south) and consistent adverse treatment related effects were not noted for any taxa other than Phytoseiidae. At a lower rate of mancozeb representing potential off-field deposits at 3 m due to drift effects were virtually absent on predatory mites in and to all other taxa present.

Topics: Animals; Arthropods; Ecosystem; France; Fungicides, Industrial; Geography; Malus; Maneb; Mite Infestations; Mites; Plant Leaves; Zineb

The purpose of this study is to accesses the efficiency of removal of pesticide Mancozeb (Dithiocarbamates family) using different sorbents (synthetic zeolite type A, Humic Acid (HA) extracted from soil of Noshahr jungle in the north of Iran and mixture of them). The adsorption efficiency of the adsorbents was evaluated by Freundlich isotherms to select the best sorbent. The main effective parameters such as the amount of sorbents, pH, agitating time and concentrations of Mancozeb were tested. The results for 1.6 ppm of pesticide at pH=5 shows the optimum values 2, 0.75, 0.5 g for HA, zeolite NaA and mixture of them, respectively. The adsorption capacity decreases as pH increases and the adsorption effect for 0.1 g of sorbents at pH=5 were obtained in the order: (mixture of sorbents) > (synthetic zeolite type A) > (extracted Humic Acid).

Topics: Adsorption; Dose-Response Relationship, Drug; Fungicides, Industrial; Humic Substances; Hydrogen-Ion Concentration; Maneb; Nicotiana; Pesticide Residues; Soil Pollutants; Temperature; Time Factors; Zeolites; Zineb

Laboratory results of the French ANPP/CEB guideline No. 167 and IOBC/WPRS Ring Testing Group methods for testing the side effects of pesticides on the predatory mite Typhlodromus pyri Scheuten were compared with respect to their suitability to evaluate the toxicity of three pesticides.. Results obtained with the ANPP/CEB guideline allow the demonstration of significant differences between two slightly toxic products, a dichlofluanid 500 g kg(-1) kWP (Euparen) 50WP) and a quinoxyfen 250 g L(-1) SCC (Legend), and a highly toxic cymoxanil 60/mancozeb 200/folpet 275 g kg(-1) WP [Remiltine F Pepite) (RFP)], on the basis of bioassays conducted in the laboratory. In contrast, results obtained with the IOBC/WPRS method classified all three as harmful.. The evaluation of the toxicity of RFP revealed that the concentration, the quantity of the wet deposit and the food source used in the IOBC/WPRS method maximise the toxicity, in comparison with those used in the ANPP/CEB protocol. Valid criteria in controls were all respected in the ANPP/CEB tests but not in the IOBC/WPRS samples. This result revealed difficulties related to the use of the IOBC/WPRS method in laboratories.

Topics: Acari; Acetamides; Aniline Compounds; Animals; Biological Assay; Fertility; Insecticides; Larva; Maneb; Nymph; Ovum; Phthalimides; Quinolines; Reproducibility of Results; Sensitivity and Specificity; Zineb

FLR1 gene, encoding a multidrug resistance (MDR) transporter of the major facilitator superfamily (MFS) was found to confer resistance to the fungicide mancozeb in Saccharomyces cerevisiae. This agrochemical has been linked to the development of Parkinson disease and cancer. Yeast response to mancozeb was proved to involve the strong activation of FLR1 transcription (20-fold) during the fungicide-induced growth latency. This activation of FLR1 transcription is fully dependent on Yap1p and is reduced (by 50%) in the absence of Rpn4p, Yrr1p or Pdr3p. A model for the coordinate action over FLR1 transcription activation, in response to mancozeb, of these transcription factors that mediate oxidative stress response (Yap1p), proteasome gene expression (Rpn4p), and pleiotropic drug resistance (Pdr3p and Yrr1p), is proposed.

Topics: Adaptor Proteins, Signal Transducing; DNA-Binding Proteins; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Fungicides, Industrial; Gene Expression Regulation, Fungal; Maneb; Membrane Transport Proteins; Organic Anion Transporters; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Transcription Factors; Up-Regulation; Zineb

The aim was to assess the influence of mancozeb, zoxamide and copper oxychloride fungicide treatments on Mn, Zn, Cu, Cd and Pb concentrations in Sicilian red wines, grapes, marcs and grape stalks. The experimentation was carried out over two crop years: 2003 and 2004. Trace metals analysis was performed by derivative stripping chronopotentiometry, which allowed detection of concentrations lower than 1 ng g(-1). The data obtained gave evidence that the levels of Mn and Zn in wines from plots treated with zoxamide-mancozeb were about threefold higher than those observed in the control. Wines treated with Cu oxychloride had a significant increase in Cu(II) concentrations with respect to the control; in particular, samples from 2004 showed a 50% increase in Cu levels. Furthermore, as shown in a previous paper, the fungicides treatments studied led to a moderate increase in Pb(II) and Cd(II) levels in treated samples with respect to the control. Wines from 2004 had higher Cu and Pb amounts than wines from 2003; but the concentrations of all the other metals were similar. Statistical analysis of the data by linear discriminant analysis (LDA) and the Kruskal-Wallis test confirmed that both zoxamide-mancozeb treatments and copper oxychloride treatments exerted a significant influence on Mn(II), Zn(II) Cu(II), Pb(II) and Cd(II) concentrations in wines, grapes, marcs and grape stalks samples from both the studied vintages.

Topics: Amides; Cadmium; Copper; Food Contamination; Fungicides, Industrial; Lead; Linear Models; Maneb; Manganese; Metals, Heavy; Plant Shoots; Sicily; Vitis; Wine; Zinc; Zineb

Mancozeb, manganese ethylene-bis-dithiocarbamate with zinc salts, is one of the most commonly used fungicides in the United States. Epidemiological and experimental data showed that mancozeb causes detrimental effects on various organ systems including the reproductive, endocrine, immune, and central nervous system. Increasing evidence has shown a strong association between pesticides and neurodegenerative diseases. In this study, we examined the neurotoxic potential of mancozeb in rat hippocampal astrocytes. The cytotoxicity of mancozeb was found to be dose dependent and recovery studies showed that cells exposed to mancozeb for 1 h did not recover from mancozeb-induced insult. Atomic absorption data showed a significant accumulation of manganese in astrocytes after 1 h of treatment. This study further investigated whether various chelators and antioxidants could prevent mancozeb-induced cytotoxicity. Our data reported that butylated hydroxytoluene (BHT) was the most effective agent in protecting against mancozeb insult. BHT also increased total cellular antioxidants of astrocytes after 1-h mancozeb exposure. In summary, this study reported for the first time that the manganese portion of mancozeb might be, at least in part, responsible for the toxicity. Mancozeb-induced cytotoxicity in astroyctes can be protected by BHT and that this antioxidant increased the total cellular antioxidant capacity.

Topics: Animals; Animals, Newborn; Antioxidants; Astrocytes; Butylated Hydroxytoluene; Cations, Divalent; Cell Survival; Chelating Agents; Dose-Response Relationship, Drug; Fungicides, Industrial; Hippocampus; In Vitro Techniques; Male; Maneb; Manganese; Rats; Rats, Sprague-Dawley; Zinc; Zineb

It is not clear so far whether alteration of leaf micromorphology and surface wax chemistry due to the impact of environmental factors, such as UV-B radiation, affects retention and rainfastness of applied pesticide solutions. In this study; UV-B treated and untreated adaxial leaf surfaces of apple seedlings (Malus domestica Borkh.) were characterized in terms of chemical composition, micromorphological fine structure, hydrophobicity, and wettability. Furthermore, the retention and rainfastness of applied fungicide mancozeb were studied. The samples were examined 0, 24 and 48 h after ultraviolet (UV)-B radiation (0.022 kW m(-2) for 150 min) The total wax mass, recovered from the adaxial leaf surface, amounted from 0.38 microg cm(-2) (control) up to 0.49 microg cm(-2) (24 h). Chemical composition of surface wax altered, whereas the contact angle of applied water droplets on leaf surface of UV-B treated plants did not change significantly compared to the control. The alteration of surface wax quantity and quality significantly affected retention of a.i.; it increased at a sampling time of 24 h after UV-B irradiation, whereas rainfastness of the fungicide spray solution was not significantly influenced.

Topics: Crops, Agricultural; Fungicides, Industrial; Malus; Maneb; Plant Epidermis; Plant Leaves; Rain; Seedlings; Time Factors; Ultraviolet Rays; Waxes; Zineb

The effect of Dithane M-45 (dithiocarbamate fungicide; active substance: mancozeb) was studied on microarthropod fauna inhabiting dead wood. Although the exposure was almost never 100% lethal for the majority of observed taxa, almost all (Mesostigmata, Oribatida, some Uropodina, Actinedida, Collembola and Diplopoda) showed very high correlation between concentration of the fungicide and mortality (r > 0.86). Only Stigmaeidae showed low correlation (r = 0.293). For the majority of taxa LC(50 )values were close to the concentrations used during agrochemical activities in woods. Only Trachytes aegrota showed full susceptibility to the fungicide within the range of recommended field concentrations used in forestry (characterised by the low LC(95 )value). Tolerance of mesostigmatid and oribatid mites was found to differ between juveniles and adults, but not consistently. Related Uropodina species varied in susceptibility to the fungicide.

Topics: Animals; Arthropods; Fungicides, Industrial; Lethal Dose 50; Maneb; Wood; Zineb

Two species of Phytoseiidae predominated in and around vineyards in an experimental site in the south of France: Typhlodromus exhilaratus is the dominant species on grapes, whereas T. phialatus occurs in the uncultivated areas surrounding these crops. To help understand their distribution, this study aims to determine their susceptibility to a fungicide (dimethomorph + mancozeb) and an insecticide (chlorpyriphos-ethyl), which have been widely used at the experimental site for at least four years. The hypothesis tested is that the effects of these two pesticides differ between T. exhilaratus and T. phialatus. Two populations of T. exhilaratus, one collected on a vine crop where the two pesticides were applied and the other in an unsprayed orchard of Sorbus domestica, and one population of T. phialatus collected on Viburnum tinus from uncultivated areas adjacent to the vine crop, were tested under laboratory conditions. The fungicide seems to affect the females of T. phialatus more than those of T. exhilaratus from vine. However, at the recommended field concentration the female mortality rates of the three strains were low and female fecundities were not significantly different. Conversely, mortality rates were very high for the three strains at the recommended field concentration of chlorpyrifos-ethyl. The strain of T. exhilaratus from vine seems to be more tolerant and 20% of females survived the recommended field rate. This suggests better survival after insecticide application than females of T. phialatus (100% mortality at a lower concentration than the recommended rate). As extrapolation of laboratory results to the field is often irrelevant, these differences could be just one of several factors affecting the spatial segregation of the two species in the agrosystem considered. Possible explanations other than pesticides for the poor settlement of T. phialatus in vine plots are discussed.

Topics: Animals; Chlorpyrifos; Female; France; Fungicides, Industrial; Insecticides; Male; Maneb; Mites; Morpholines; Organothiophosphorus Compounds; Vitis; Zineb

Previous in vitro studies in our laboratory have shown that mancozeb (MZ) and maneb (MB), both widely used EBDC fungicides, are equipotent neurotoxicants that produce cell loss in mesencephalic dopaminergic and GABAergic cells after an acute 24h exposure. Mitochondrial uncoupling and inhibition were associated with fungicide exposure. Inhibition of mitochondrial respiration is known to increase free radical production. Here the mechanism(s) of neuronal damage associated with MZ exposure was further explored by determining the role that reactive oxygen species (ROS) played in toxicity. Damage to mesencephalic dopamine and GABA cell populations were significantly attenuated when carried out in the presence of ascorbate or SOD, indicative of a free radical-mediated contribution to toxicity. ROS generation monitored by hydrogen peroxide (H(2)O(2)) production using Amplex Red increased in a dose-dependent manner in response to MZ. Inhibition of intracellular catalase with aminotriazole had little effect on H(2)O(2) generation, whereas exogenously added catalase significantly reduced H(2)O(2) production, demonstrating a large extracellular contribution to ROS generation. Conversely, cells preloaded with the ROS indicator dye DCF showed significant MZ-induced ROS production, demonstrating an increase in intracellular ROS. Both the organic backbone of MZ as well as its associated Mn ion, but not Zn ion, were responsible and required for H(2)O(2) generation. The functionally diverse NADPH oxidase inhibitors, diphenylene iodonium chloride, apocynin, and 4-(2-aminoethyl)benzene-sulfonyl fluoride hydrochloride significantly attenuated H(2)O(2) production by MZ. In growth medium lacking cells, MZ produced little H(2)O(2), but enhanced H(2)O(2) generation when added with xanthine plus xanthine oxidase whereas, in cultured cells, allopurinol partially attenuated H(2)O(2) production by MZ. Minocycline, an inhibitor of microglial activation, modestly reduced H(2)O(2) formation in mesencephalic cells. In contrast, neuronal-enriched cultures or cultures treated with MAC-1-SAP to kill microglia, did not show an attenuation of ROS production. These findings demonstrate that Mn-containing EBDC fungicides such as MZ and MB can produce robust ROS generation that likely occurs via redox cycling with extracellular and intracellular oxidases. The findings further show that microglia may contribute to but are not required for ROS production by MZ.

Topics: Acetophenones; Allopurinol; Amitrole; Animals; Antioxidants; Ascorbic Acid; Catalase; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fungicides, Industrial; Hydrogen Peroxide; Maneb; Mesencephalon; Microglia; Minocycline; Molecular Structure; NADPH Oxidases; Neurons; Onium Compounds; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Structure-Activity Relationship; Sulfones; Superoxide Dismutase; Time Factors; Xanthine Oxidase; Zineb

The DNA damaging and proapoptotic effects of Mancozeb, a widely used fungicide of the ethylene-bis-dithiocarbamate (EBDC) group, were studied in RAT-1 fibroblasts cultured in vitro and in peripheral blood mononucleated cells (PBMC) isolated from Wistar rats. After 1 h exposition to Mancozeb (up to 500 ng/ml), cells produced a dose-dependent induction in DNA single strand break (SSB) formation, measured by single cell gel electrophoresis (SCGE). Concomitantly, a concentration-dependent increase in the levels of the oxidative markers of DNA oxidation, the DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) and of reactive oxygen species (ROS) were observed, suggesting a prooxidant action of Mancozeb. PBMC were less responsive than fibroblasts to the oxidative insult carried out by Mancozeb, as shown by the lower increase in the levels of ROS, 8-OHdG adducts and SSB measured in these cells after exposure to the pesticide. A 4-h treatment with Mancozeb induced also apoptosis in both PBMC and RAT-1 cells, even though leukocytes were less sensitive than fibroblasts to the proapoptotic action. This effect was dose-dependent and was inhibited by the action of the antioxidant alpha-tocopherol. The proapoptotic effect was accompanied by the altered expression of several proteins involved in the regulation of apoptosis, such as the prosurvival protein BCL-2 and the proapoptotic protein c-MYC. Exposition of cells to higher concentrations of Mancozeb or for longer periods (>4 h) caused post-apoptotic, necrotic alterations in cell membrane integrity. The data herein presented demonstrate the oxidative effect of Mancozeb and suggest that its prooxidant action may be involved in the proapoptotic effect exerted by this compound in rat cells. It appears possible that the observed oxidative and genotoxic damage may be involved in the pathogenesis of various pathologies associated with the chronic exposition to Mancozeb, including cancer. On the other hand, the proapoptotic effect of Mancozeb suggests its possible relevance in the pathogenesis of neurodegenerative diseases, often related to the exposition of pesticides.

Topics: 8-Hydroxy-2'-Deoxyguanosine; alpha-Tocopherol; Animals; Apoptosis; Blotting, Western; Cell Line; Cell Survival; Comet Assay; Deoxyguanosine; DNA Damage; Dose-Response Relationship, Drug; Fibroblasts; Fungicides, Industrial; Hydrogen Peroxide; In Situ Nick-End Labeling; Leukocytes, Mononuclear; Maneb; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Rats; Rats, Wistar; Reactive Oxygen Species; Time Factors; Vitamins; Zineb

Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc salt, is widely used in agriculture as fungicide. Literature data indicate that ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans. We have recently found in agricultural workers occupationally exposed to the fungicide mancozeb a statistically significant decrease in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is an essential proinflammatory cytokine whose production is normally stimulated during an infection. The purpose of this work was to establish an in vitro model reflecting in vivo data and to characterize the molecular mechanism of action of mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations (1-100 microg/ml), induced a dose- and time-dependent inhibition of LPS-induced TNF release, reflecting in vivo data. The modulatory effect observed was not limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar inhibitory effects. Mancozeb must be added before or simultaneously to LPS in order to observe the effect, indicating that it acts on early events triggered by LPS. It is known that nuclear factor-kappaB (NF-kappaB) tightly regulates TNF transcription. We could demonstrate that mancozeb, modulating LPS-induced reactive oxygen species generation, prevented IkappaB degradation and NF-kappaB nuclear translocation, which in turn resulted in decreased TNF production. To further understand the mechanism of the effect of mancozeb on TNF transcription, THP-1 cells were transfected with NF-kappaB promoter-luciferase construct, and the effect of mancozeb on luciferase activity was measured. Cells transfected with promoter constructs containing kappaB site showed decreased LPS-induced luciferase activity relative to control after mancozeb treatment, confirming NF-kappaB binding as an intracellular target of mancozeb. Overall, this study contributes to our understanding of the mechanism underlying mancozeb-induced immunotoxicity.

Topics: Biotransformation; Blotting, Western; Cell Line; Cell Line, Tumor; Dose-Response Relationship, Drug; Ethylenethiourea; Fungicides, Industrial; Genes, Reporter; Humans; L-Lactate Dehydrogenase; Lipopolysaccharides; Maneb; NF-kappa B; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors; Transcription, Genetic; Tumor Necrosis Factor-alpha; Zineb; Ziram

Mancozeb is known to alter reproductive performance in exposed animals, but its specific mechanism of action is still unclear. We investigated whether in female mice of the F1 generation, mancozeb could affect oocyte ability to undergo complete meiotic maturation and fertilization. Female mice were treated with 50 and 500 mg/kg of mancozeb (or vehicle in the controls) from gestational day 2 to postnatal day 20. Results demonstrated that only at the highest dose, mancozeb induced a significant decrease in the number of ovulated eggs. Moreover, at this dose mancozeb caused a significant decrease of fertilizability related to a reduction of the formation of male and female pronuclei.

Topics: Animals; Female; Fertilization in Vitro; Fungicides, Industrial; Male; Maneb; Meiosis; Mice; Oocytes; Spermatozoa; Zineb

In this study the effects of mancozeb, a widely used ethylenebisdithiocarbamate fungicide, on mouse oocyte meiotic maturation and fertilization were analyzed. Oocyte cumulus cell-complexes were matured in vitro with or without increasing concentrations of the fungicide (from 0.001 to 1 microg/ml) that, due to its different stability in organic solvents and in water, was resuspended either in dimethyl sulfoxide or in culture medium. Although, about 95% of oocytes reached the metaphase II stage; mancozeb-exposed oocytes showed a dose-dependent increase of alterations in spindle morphology, and this negative effect was more evident when the fungicide was resuspended in culture medium. Under the latter culture condition, oocytes matured in the presence of 0.1 and 1 microg/ml mancozeb showed a significant reduction also in the formation of male and female pronuclei. These results indicate that mancozeb can adversely affect mammalian reproductive performance, likely by perturbing microtubular organization during meiotic maturation.

Topics: Animals; Chromosomes, Mammalian; Dose-Response Relationship, Drug; Female; Fertilization in Vitro; Fungicides, Industrial; Male; Maneb; Meiosis; Metaphase; Mice; Microscopy, Fluorescence; Microtubules; Oocytes; Spindle Apparatus; Zineb

Resistance to QoI fungicides (strobilurins, famoxadone and fenamidone) in populations of Plasmopara viticola (Berk & Curt) Berlese & de Toni developed soon after their introduction in France and Italy. Current resistance management strategies include limitation of the number of applications, use of mixtures and alternation of fungicides with different modes of action. The selection pressure resulting from QoI fungicides applied alone or in mixtures with non-QoI fungicides was investigated in whole plant experiments under controlled conditions. QoI-resistant populations of P. viticola gradually reverted to full sensitivity following consecutive transfers to untreated plants, suggesting that resistant phenotypes were less competitive than sensitive ones. When cycled on QoI-treated plants, reduction in sensitivity was greater for the QoI fungicide which had greater intrinsic activity on P. viticola. Sensitivity decreased at each subsequent cycle, resulting in almost full resistance after four generations. Mixture experiments indicated that selection pressure was affected most by the dose of the QoI fungicide and the nature of the partner fungicide. Folpet delayed selection pressure most effectively when it was associated with famoxadone or azoxystrobin. Mancozeb was least effective at reducing the rate of selection compared with the QoI alone, and fosetyl-aluminium was intermediate. Higher rates of selection were recorded when the dose of the QoI fungicide, solo or in a mixture, was increased from 1 to 4 microg ml(-1). Increasing the dose of the non-QoI partner fungicide in the mixture from 10 to 30 microg ml(-1) resulted in reduced selection pressure. These results suggest that the choice of the fungicide partner and its dosage in the mixture can significantly affect the success of QoI resistance management strategies under practical conditions.

Topics: Drug Interactions; Drug Resistance, Fungal; Fungicides, Industrial; Imidazolines; Maneb; Methacrylates; Oomycetes; Organophosphorus Compounds; Oxazoles; Phthalimides; Plant Diseases; Pyrimidines; Selection, Genetic; Strobilurins; Vitis; Zineb

Topics: Animals; Cell Nucleus; Cichlids; Fungicides, Industrial; Glycogen; Hepatocytes; Hepatopancreas; Macrophages; Maneb; Mast Cells; Models, Animal; Water Pollutants, Chemical; Zineb

To study the dominant seed-borne fungi of Glycyrrihiza seeds which were from different producing area and compare the disinfection effect of several fungicides on seed-borne fungi of Glycyrrihiza seed.. Petri-dish testing was used to determine the external and internal seed-borne fungi and the disinfection effect of fungicides.. The result showed that the amount of spore on the surface of one Glycyrrihiza seed varied from 0.3% to 37.0% among samples. Penicillium spp. and Aspergillus spp. were the two major dominant fungi and there was few differences in the type of the fungi among producing areas but differences in the isolation frequency of the furgi; Penicillium spp. , Rhizopus spp. , Aspergillus spp. and Alternaria spp. were the internally dominant seed-borne fungi, including seed capsule and the internal tissue of seed and their fungi-carrying percentage was 8.0%-48.3% and 3.5%-42.0% respectively. There were differences in fungi percentage and dominant seed borne fungi among different producing areas. The disinfection effect of both mancozeb and thriam was up to 89.0%, so it is suggested to use them to disinfect Glycyrrihiza seed.

Topics: Aspergillus; Fungicides, Industrial; Glycyrrhiza uralensis; Maneb; Penicillium; Plants, Medicinal; Rhizopus; Seeds; Zineb

A study was made of the influence of the upper leaf surface characteristics on the retention and rainfastness of the contact fungicide mancozeb with and without tank-mix adjuvants (RSO 5 and RSO 60) on apple seedlings, bean seedlings and kohlrabi plants. Large differences in roughness, in the amount and composition of surface waxes and in the retention and rainfastness of mancozeb were found among species. Strong correlations between roughness and total amount of surface waxes and mass of C29 alkane in the wax mass were also found. Fungicide retention was strongly, negatively correlated with surface roughness, total epicuticular wax, amount of C29 alkane and the total mass of alkanes. Rainfastness correlated strongly or very strongly with the amount of C28 alcohol and C33 alkane. The addition of a more hydrophobic (RSO 5) or a more hydrophilic (RSO 60) adjuvant to the spray solution influenced retention and rainfastness, and also altered the correlation coefficients. The present results support earlier observations which show that the success of adjuvants in enhancing the retention and rainfastness of agrochemicals depends on the characteristics of the leaf surface.

Topics: Adjuvants, Pharmaceutic; Alkanes; Brassica; Crops, Agricultural; Fungicides, Industrial; Malus; Maneb; Phaseolus; Plant Epidermis; Plant Leaves; Rain; Seedlings; Waxes; Zineb

Recent studies suggest that exposure to agrochemicals may contribute to the development of idiopathic Parkinson's disease. Maneb (MB), a widely used Mn-containing ethylene-bis-dithiocarbamate (EBDC) fungicide, has been implicated in selective dopaminergic neurotoxicity. In this study, we examine the potential neurotoxicity of mancozeb (MZ), a widely used EBDC fungicide that is structurally similar to MB, but contains both Zn and Mn. Primary mesencephalic cells isolated from Sprague-Dawley embryonic day 15 rat embryos were exposed in vitro to either MZ or MB to compare their cytotoxic potential. Exposure to 10-120 microM MZ or MB for 24h resulted in a dose-dependent toxicity in both the dopamine (DA) and GABA mesencephalic populations as assessed by a functional assay for high affinity transporter activity. Consistent with this, cell viability as well as tyrosine hydroxylase-positive neurons decreased with increasing doses of MZ or MB. Toxic potencies for MZ and MB were similar and no difference in sensitivity between the DA and GABA populations was observed with the fungicides. Exposure to ethylene thiourea, the major metabolite of either MZ or MB, was not toxic, implicating the parent compound in toxicity. Both the organic and Mn metal components of the fungicides were found to contribute to toxicity. Non-toxic exposures to the fungicides decreased ATP levels in a dose-dependent manner suggesting impairment of energy metabolism. In whole mitochondrial preparations isolated from adult rat brains, MZ and MB inhibited NADH-linked state 3 respiration. Mild to moderate mitochondrial uncoupling was also observed in response to the fungicides. In conclusion, our findings indicate that acute exposure to high doses of MZ and MB produce equipotent toxic effects in both DA and GABA neurons that may be associated with perturbations in mitochondrial respiration.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Cell Survival; Cells, Cultured; Dopamine; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fungicides, Industrial; gamma-Aminobutyric Acid; Male; Maneb; Mesencephalon; Mitochondria; Neurons; Oxygen Consumption; Pregnancy; Rats; Rats, Sprague-Dawley; Tyrosine 3-Monooxygenase; Zineb

We have previously shown that a single i.p. injection of nitrosomethylurea (NMU) in 3-day-old rats orally treated with the pesticide mancozeb (MZ), the flavonoid quercetin (Q) or in combination (MZ-Q) induces hyperplasia, atypical acinar cell proliferation and carcinoma in situ (CIS) in the pancreas. This work studies the effect of oral administration of phenobarbital (PB) on this model of pancreatic carcinogenesis. The animals were fed on a diet supplemented by MZ or/and Q from the 10th day of pregnancy, thorough lactation and as pups after weaning until being sacrificed at week 24. Saline injection with non-supplemented diet was used for the control group (SAL). The experimental groups were (1) SAL (control), (2) SAL-PB, (3) NMU, (4) NMU-PB, (5) MZ-NMU, (6) MZ-NMU-PB, (7) Q-NMU, (8) Q-NMU-PB, (9) MZ-Q-NMU and (10) MZ-Q-NMU-PB. Acinar cell hyperplasia was found in all groups of NMU-treated rats. Dysplastic foci (DYS) were seen in groups 3-10 at the following percentages: 19, 48, 71, 27, 71, 35, 100 and 30, respectively. CIS were recorded in groups 4 to 10 at percentages: 4, 36, 13, 11, 0, 16, 5, respectively.. Although PB, Q or MZ given alone enhance DYS lesions in NMU-treated rats, the MZ/Q/PB combined treatments may increase (mainly in males) or decrease (mainly in female) the DYS and CIS proportion. Because PB, MZ and Q influence P450 enzymes, we suggest that these enzymes play a role in the carcinogenesis process.

Topics: Alkylating Agents; Animals; Animals, Newborn; Carcinogens; Carcinoma in Situ; Disease Models, Animal; Drug Interactions; Drug Therapy, Combination; Female; Fungicides, Industrial; Hyperplasia; Maneb; Maternal Exposure; Maternal-Fetal Exchange; Methylnitrosourea; Pancreatic Neoplasms; Phenobarbital; Pregnancy; Quercetin; Rats; Rats, Wistar; Zineb

Mancozeb is a dithiocarbamate fungicide with contact activity against a wide range of economically important fungal diseases. Its multi-site mode of action means that to date there have been no recorded incidences of resistance developing despite many years of use on high risk diseases. One such disease, Grape downy mildew (Plasmopara viticola) has developed resistance to a wide range of important oomycete specific fungicides following their introduction onto the market. The role of Mancozeb either as a mixing or alternation partner in helping to manage these resistance situations remains critically important. Historical use patterns for mancozeb in tree and vine crops involved many applications of product at high use rates. Although this gave excellent disease control, a negative impact on predatory mites was often reported by researchers. This has lead to the development of mancozeb spray programmes in vines and other crops with a much reduced impact on predatory mites. A range of field studies was conducted over two years in France, Germany, Italy, Portugal and Spain where 2, 3 or 4 applications of mancozeb containing products were made per season at different spray timings. In this paper findings from field studies over two years in five different vine growing regions in Europe indicated that two to four applications of mancozeb at 1.6 kg a.i./ha as part of a spray programme caused minimal impact on naturally occurring populations of predatory mites which in turn was compatible with Integrated Pest Management programmes and the conservation of predatory mites.

Topics: Animals; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Europe; Fungicides, Industrial; Maneb; Mites; Seasons; Vitis; Zineb

Use of plant products for the management of phytopathogenic fungi is fast becoming an important component of Integrated Disease Management (I.D.M.) programme. The natural plant products are bio-degradable and thus eco-friendly, are catching the attention of the scientist worldwide. Such products from higher plants are relatively broad spectrum, bio-efficacious, economical and environmentally safe. Among these essential oils from higher plants because of their greater inhibitory action are being explored preferably worldwide. In this context, a study was undertaken to explore the effect of volatile oil from Eucalyptus citriodora against Alternaria triticina. The radial growth, dry weight and spore germination of pathogen were drastically reduced in response to the different concentrations of volatile oil. A complete inhibition of radial growth, dry weight and spore germination were observed at 1500, 1000 and 100 ppm, respectively. In contrast, similar complete inhibition of test pathogen was observed at very high concentration (6500, 6500 and 1000 ppm) of mancozeb--a commercially available synthetic fungicide. Based on these observations, it was therefore concluded that eucalypt volatile oil has potential to suppress the phytopathogenic fungi.

Topics: Alternaria; Eucalyptus; Eucalyptus Oil; Fungicides, Industrial; Germination; Maneb; Monoterpenes; Oils, Volatile; Plant Diseases; Plant Leaves; Zineb

Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis factor-alpha (TNF-alpha) synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 (TNF-alpha) or 3 days (NO) in the presence of LPS plus IFN-gamma. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 microg/mIL in the presence of LPS plus IFN-gamma for 2 (TNF-alpha) or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed TNF-alpha secretion with significant reduction at 2 microg/mL MCZ. Conversely, TNF-alpha release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and TNF-alpha synthesis.

Topics: Animals; Dose-Response Relationship, Drug; Female; Macrophages, Peritoneal; Maneb; Mice; Mice, Inbred ICR; Nitrites; Tumor Necrosis Factor-alpha; Zineb

The fungicide mancozeb has been suspected of causing thyroid cancer and neural tube defects. The aim of the study was to investigate associations of indicators of mancozeb exposure with thyroid cancer and neural tube defects in farmers' families.. National registers in Norway, identifying 105 403 female and 131 243 male farmers, born in 1925-1971, and their 300 805 children available for analyses, born in 1952-1991, were cross-linked with national agricultural censuses, 1969-1989, and the population register. Neural tube defects (ICD-8 740-742) at birth among the 102 703 children conceived between May 1973 and April 1991 were identified in the medical birth register. Likewise thyroid cancer (ICD-7 194) was identified in the cancer register through 2000. Data on farm production and fungal forecasts (humid and temperate weather conditions) in 1973-1990, obtained from agricultural censuses and meteorological measurement stations, respectively, served as the mancozeb exposure indicators. The adjusted rate ratio or prevalence ratio (PR) estimates with 95% confidence intervals (95% CI) were computed in a Poisson regression analysis.. Neural tube defects (131 cases, prevalence 12.8/10 000 births) was moderately associated with potato cultivation (PR 1.6, 95% CI 1.1-2.3) and paternal work of > 500 hours/year (PR 1.6, 95% CI 1.1-2.5). Altogether 319 thyroid cancer cases were identified: 141 in female farmers (incidence 10.2/100 000 person-years), 79 in male farmers (incidence 3.2/100 000 person-years), and 99 in offspring (female and male incidence 3.4 and 0.6/100 000 person-years, respectively). Mancozeb exposure was not associated with thyroid cancer.. A moderate association seems to exist between mancozeb exposure and neural tube defects, but not between mancozeb exposure and thyroid cancer.

Topics: Agriculture; Family; Female; Fungicides, Industrial; Humans; Male; Maneb; Neural Tube Defects; Norway; Occupational Exposure; Prevalence; Registries; Risk Factors; Thyroid Neoplasms; Zineb

Available data suggest that ethylenebisdithiocarbamates (EBDCs) may have immunomodulatory effects. This study aimed to investigate the immunological profile of farmers exposed to Mancozeb, an EBDC fungicide, through the determination of several serum, cellular, and functional immune parameters. Twenty-six healthy subjects entered the study, 13 vineyards exposed to Mancozeb and 13 unexposed controls. Exposure was assessed through the determination of ethylentiourea (ETU) in urine. Complete and differential blood count, serum immunoglobulins, complement fractions, autoantibodies, lymphocyte subpopulations, proliferative response to mitogens, natural killer (NK) activity, and cytokine production were measured. Post-exposure samples showed ETU urine concentration significantly higher than pre-exposure and control groups. A significant increase in CD19+ cells, both percentage and absolute number, and a significant decrease in the percentage of CD25+ cells were found in post-exposure samples compared to controls. A statistically significant increase in the proliferative response to phorbol myristate acetate plus ionomycin (PMA + ionomycin) was observed in the post-exposure group compared to controls and baseline, while a significant reduction in LPS-induced TNF-alpha release in post-exposure samples was observed. Overall, our results suggest that low-level exposure to Mancozeb has slight immunomodulatory effects, and point out a method adequate to reveal immune-modifications in workers occupationally exposed to potential immunotoxic compounds, based on a whole blood assay.

Topics: Adult; Agriculture; Blood Cell Count; Carcinogens; Cytokines; Dose-Response Relationship, Drug; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Immune System; Immunoglobulins; Immunologic Factors; Killer Cells, Natural; L-Lactate Dehydrogenase; Lymphocyte Count; Lymphocyte Subsets; Male; Maneb; Middle Aged; Occupational Exposure; Zineb

To develop a pilot-plant fermentation process for the production of the yeast Rhodotorula minuta, to be used as a biocontrol agent of mango anthracnose, using a low-cost culture medium. To develop a stable liquid formulation that preserve high viability of the yeast stored at 4 degrees C.. Keeping constant the volumetric power input, a fermentation process was scaled-up from shake flasks to a 100 l bioreactor. Preharvest applications of the yeast resulted in postharvest anthracnose severity equal or lower than that observed with a chemical fungicide. Glycerol was added to the formulation as water activity reducer and xanthan gum as a viscosity-enhancing agent. Yeast initial concentration of 10(10) CFU ml(-1) resulted in 4-5 orders of magnitude decrease after 1 month of storage at 4 degrees C, whereas when it was formulated at 10(9) CFU ml(-1), the decrease was of two orders of magnitude in 6 months.. The fermentation process was successfully scaled-up using a low-cost culture medium. Postharvest anthracnose severity could be considerably reduced using this yeast. Formulating the yeast at 10(9) CFU ml(-1) and adding glycerol (20%) and xanthan (5 g l(-1)) avoided both contamination and yeast sedimentation and it was able to preserve up to 10(7) CFU ml(-1) after 6 months at 4 degrees C.. The yeast R. minuta is reported as a novel antagonistic micro-organism against the pathogen Colletotrichum gloeosporioides. Pilot plant production of this yeast allowed us to conduct field tests in commercial orchards during three harvest seasons. Yeast suspensions applied to mango trees reduced the fruit anthracnose severity in levels similar or better than chemical fungicides.

Topics: Biomass; Colony Count, Microbial; Cryoprotective Agents; Culture Media; Fermentation; Food Additives; Fungicides, Industrial; Glycerol; Maneb; Mangifera; Microbial Viability; Pest Control, Biological; Plant Diseases; Polysaccharides, Bacterial; Rhodotorula; Temperature; Viscosity; Zineb

Agricultural risk factors for lymphohematopoietic cancers (LHC) in Hispanic farm workers in California were examined in a nested case-control study embedded in a cohort of 139,000 ever members of a farm worker labor union in California.. Crop and pesticide exposures were estimated by linking county/month and crop specific job history information from union records with California Department of Pesticide Regulation pesticide use reports during the 20-year period prior to cancer diagnosis.. A total of 131 LHC diagnosed in California between 1988 and 2001 were included in the analysis. Analyses were conducted by gender and subtype of non-Hodgkins lymphoma (nodal, extra nodal) and by leukemia histology (lymphocytic, granulocytic). Odds ratios were calculated by stratification and by unconditional logistic regression. Risk for all LHC was elevated in workers cultivating vegetables (OR = 1.67, 95% CI = 1.12-2.48). Risk of leukemia was associated with exposure to the pesticides mancozeb (OR = 2.35, 95% CI = 1.12-4.95) and toxaphene (OR = 2.20, 95% CI = 1.04-4.65) while NHL risk was increased in association with 2,4-D (OR = 3.80, 95% CI=1.85-7.81). Risk of leukemia was particularly elevated among female workers and for granulocytic versus lymphocytic leukemia for several chemicals. No associations were noted for multiple myeloma.. California farm workers employed where mancozeb and toxaphene were used had an increased risk of leukemia compared to farm workers employed elsewhere. Employment in farms using 2,4-D was associated with an increased risk of NHL.

Topics: Agricultural Workers' Diseases; California; Case-Control Studies; Female; Fungicides, Industrial; Hispanic or Latino; Humans; Insecticides; Leukemia, Lymphoid; Leukemia, Myeloid; Logistic Models; Lymphoma, Non-Hodgkin; Male; Maneb; Multiple Myeloma; Multivariate Analysis; Occupational Exposure; Odds Ratio; Pesticides; Risk Factors; Sex Factors; Toxaphene; Zineb

We have tested whether some pesticides might cause inner membrane leakage in ML35 Escherichia coli cells, which express beta-galactosidase (lacZ; EC 3.2.1.23) constitutively but lack the permease (lacY) required for substrate entry. The activity of beta-galactosidase (indicative of substrate leakage through the inner membrane) was increased by various concentrations of pesticides, including the organometallic fungicides maneb and mancozeb, the insecticide Thiodan, and the herbicide Ally, as well as by antibiotics such as ampicillin, gramicidin D, and the calcium ionophore A23187. The enzyme activity was increased by up to approximately 30% when the E. coli ML35 strain was exposed to various concentrations (between 50 and 250 ppm) of both fungicides. Thiodan had only a slight effect on beta-galactosidase activity (increase of 12.8%), whereas, among the antibiotics, the calcium ionophore at 20 microg/ml caused a significant increase in enzyme activity by up to 61.8%. This effect is similar to that of sodium dodecyl sulfate, used as positive control ( approximately 70% increase). Accumulation of maneb and mancozeb by bacterial cells was also studied taking advantage of their metal content and using atomic absorption spectrophotometry. In parallel with the increase in enzyme activity, both fungicides accumulated in the cells as a function of their concentration. Time course experiments (3, 6, and 9 h) of fungicide accumulation and of bacterial growth at various pesticide concentrations were also carried out. Maneb seems to inhibit the bacterial growth better than mancozeb. In addition, maneb uptake increases with time up to 9 h at all tested concentrations, whereas the accumulation of mancozeb is similar at all the exposure times tested. This indicates a different uptake and/or metabolizing strategy by E. coli cells for the two fungicides.

Topics: Ampicillin; Anti-Bacterial Agents; Arylsulfonates; beta-Galactosidase; Calcimycin; Cell Membrane Permeability; Endosulfan; Enzyme Activation; Escherichia coli; Fungicides, Industrial; Gramicidin; Ionophores; Maneb; Microbial Viability; Pesticides; Sodium Dodecyl Sulfate; Zineb

A field population of Typhlodromus pyri (Acari: Phytoseiidae) tolerant to mancozeb was selected in the laboratory. After 10 mancozeb selections the LC50 value for mancozeb was 73 times higher in the selected-10 strain compared to the standard susceptible strain. A genetic analysis using reciprocal crosses and backcrosses of female F1 progeny found no maternal effect. Resistance in the selected-10 strain was codominant in expression, dominance value was about -0.1. Backcrosses between F1 females and the susceptible strain indicate that the resistance to mancozeb could be principally conferred by a predominant gene, but additional factors would also be involved.

Topics: Animals; Crosses, Genetic; Drug Resistance; Female; Fungicides, Industrial; Male; Maneb; Mites; Selection, Genetic; Zineb

The goal of this study was to analyze the effects of prenatal exposure to the pesticides paraquat (PQ) and mancozeb (MZ) on the development of synaptic transmission in mouse cerebellar cortex. Pregnant NMRI mice were treated with either saline, 10 mg/kg PQ, 30 mg/kg MZ or the combination of PQ + MZ, between gestational days 12 (E12) and E20. Variation in the levels of amino acid neurotransmitters was determined by HPLC, between postnatal day 1 (P1) and P30. Motor coordination was assessed by locomotor activity evaluation of control and experimental pups at P14, P21 and P30. Significant reductions in the levels of excitatory neurotransmitters, aspartate and glutamate, were observed in PQ-, MZ- or combined PQ + MZ-exposed pups, with respect to control, during peak periods of excitatory innervation of Purkinje cells: between P2-P5 and P11-P15. However, at P30, lower aspartate contents, in contrast with increased glutamate levels, were detected in all experimental groups. During the first two postnatal weeks, delays in GABA and glycine ontogenesis were observed in PQ- and PQ + MZ-exposed pups, whereas notable decrements in GABA and glycine levels were seen in PQ + MZ-exposed animals. Decreased taurine contents were detected at P3 and P11 in PQ- and PQ + MZ-exposed mice. Pups in different experimental groups all showed hyperactivity at P14 and then exhibited reduced locomotor activity at P30. Taken together, our results indicate that prenatal exposure to either PQ or MZ or the combination of both could alter the chronology and magnitude of synaptic transmission in developing mouse cerebellar cortex.

Topics: Animals; Aspartic Acid; Cerebellar Cortex; Disease Models, Animal; Down-Regulation; Female; Fungicides, Industrial; gamma-Aminobutyric Acid; Glutamic Acid; Glycine; Herbicides; Hyperkinesis; Maneb; Mice; Motor Activity; Neural Inhibition; Paraquat; Pregnancy; Prenatal Exposure Delayed Effects; Synaptic Transmission; Zineb

The pest leafminers Liriomyza huidobrensis (Blanchard), Liriomyza sativae (Blanchard), and Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) have spread into South East Asia and Oceania, and they are likely to reach Australia in the near future. Two translaminar pesticides, cyromazine and abamectin, currently provide effective chemical control of these pests, but because parasitoids can play an important role in controlling and preventing leafminer outbreaks, understanding the impact of pesticides on leafminer parasitoids is vital. Here, we tested larval and pupal mortality and sublethal effects of abamectin, cyromazine, and the widely used fungicide mancozeb on two common Australian leafminer parasitoids, Hemiptarsenus varicornis (Girault) and Diglyphus isaea (Walker). Abamectin caused significant mortality to larvae and pupae of both parasitoid species but cyromazine and mancozeb did not. Progeny production and longevity of H. varicornis were not affected by adult exposure to cyromazine and mancozeb, nor did direct pupal exposure decrease number of progeny produced by either parasitoid. Mortality of H. varicornis females emerging from leaves treated with abamectin was high for up to 72 h after eclosion but those surviving beyond 72 h did not differ from control females in the number of progeny produced. Mancozeb did not influence leaf residence time or parasitism by H. varicornis females. Cyromazine and the fungicide mancozeb were concluded to be compatible with the parasitoids tested and suitable for integrated pest management of leafminers should outbreaks of pest species occur in Australia. Abamectin should be used with caution because it caused significant mortality in both parasitoids tested here.

Topics: Animals; Australia; Diptera; Female; Hymenoptera; Insecticides; Ivermectin; Longevity; Maneb; Pupa; Reproduction; Triazines; Zineb

Mancozeb is an ethylene bisdithiocarbamate (EBDC) fungicide with contact activity against a wide range of economically important fungal diseases. Its multi-site mode of action means that to date there have been no recorded incidences of resistance developing despite many years of use on high risk diseases. One such disease, Grape downy mildew (Plasmopara viticola) has developed resistance to a number of important oomycete specific fungicides following their introduction onto the market. The role of Mancozeb either as a mixing or alternation partner in helping to manage these resistance situations remains critically important. Historical use patterns for mancozeb in tree and vine crops involved many applications of product at high use rates. Although this gave excellent disease control, a negative impact on predatory mites has been reported by researchers. This has lead to the development of mancozeb spray programmes in vines and other crops with a much reduced impact on predatory mites. A range of field studies was conducted in France, Germany, Italy, Portugal and Spain where either 2 or 4 applications of mancozeb containing products were made per season at different spray timings. These trials covered the representative range of uses, agronomic practices, mite species and geographical locations in Europe. In this paper findings from ten field studies in five different vine growing regions in Europe indicated that two to four applications of mancozeb at 1.6 kg a.i./ha as part of a spray programme caused minimal impact on naturally occurring populations of predatory mites which in turn was compatible with Integrated Pest Management programmes and the conservation of predatory mites.

Topics: Animals; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Europe; Fungi; Fungicides, Industrial; Geography; Insecticides; Maneb; Mites; Population Density; Predatory Behavior; Species Specificity; Time Factors; Vitis; Zineb

Many freshwater aquatic environments in the Pacific Northwest of North America contain neurotoxic pesticides, an issue of concern given the use of many of these habitats by Pacific salmon (Oncorhynchus sp.). Pesticides such as carbamates are known to affect fundamental physiological systems (such as the enzyme acetylcholinesterase (AChE)), and have been shown to affect salmonid olfactory-mediated behaviors. A neurophysiological measure of olfactory function, the electro-olfactogram (EOG), was used in this study to examine the impacts of acute localized exposure to three carbamates (the insecticide carbofuran, the antisapstain IPBC, and the fungicide mancozeb) on olfactory function in the coho salmon (Oncorhynchus kisutch). We also examine the potential for these pesticides to alter AChE levels in the primary olfactory system and brain with brief exposures (30 min to only the olfactory rosette (OR)). In results, we find that the EOG in coho salmon is highly sensitive to brief localized exposures of two of these three carbamate pesticides. The effective nominal concentration required to cause a 50% reduction in EOG amplitude (EC50) for carbofuran was 10.4 microg/l and for IPBC was 1.28 microg/l. For mancozeb, the EC50 was higher at 2.05 mg/l. All three carbamates also affected AChE activity levels in the OR and brain (BR): carbofuran exposure at 200 microg/l significantly inhibited AChE activity in the OR, and both IPBC and mancozeb significantly increased AChE activity in BR at multiple concentrations with acute localized exposure. These carbamate effects highlight the sensitivity of salmon olfactory neurophysiology to pesticides acting not only potentially via AChE-inhibition, but also by other currently unknown modes of action.

Topics: Analysis of Variance; Animals; Carbofuran; Cholinesterases; Dose-Response Relationship, Drug; Electrophysiology; Enzyme Inhibitors; Herbicides; Maneb; Oncorhynchus kisutch; Receptors, Odorant; Smell; Toxicity Tests, Acute; Zineb

The side effects of mancozeb on the predatory mite Typhlodromus pyri were studied in 4-year field trials on grapevine and in the laboratory. In the field, the effect of mancozeb varied according to previous mancozeb use. In vineyards where mancozeb had commonly been used over years, this fungicide is generally slightly toxic, in some cases moderately toxic and rarely toxic. In plots were mancozeb has never been used, its effect on T. pyri was more pronounced and varied from moderately toxic to toxic. Despite the toxicity of mancozeb, T. pyri populations have never been eradicated. Laboratory results obtained with the French CEB guideline no. 167 confirmed those of the 4-year field study: mancozeb was significantly more toxic to T. pyri populations collected in plots where it had rarely been used before the field experiment. In plots where mancozeb had been used for a long time, the susceptibility of T. pyri populations to this fungicide was reduced and female survival, fecundity but also viability of female progeny were less affected by mancozeb. Even though toxicity of mancozeb increased in controlled conditions, a significant correlation was established between field and laboratory results.

Topics: Animals; Female; Fungicides, Industrial; Maneb; Mites; Phthalimides; Statistics, Nonparametric; Vitis; Zineb

Liriomyza huidobrensis (Blanchard) and Liriomyza sativae (Blanchard) are important pests of vegetable crops in Indonesia and are likely to spread to neighboring countries. Three pesticides (dimehypo, abamectin, and cyromazine) are currently used to control these pests, but there is little information on their effectiveness against field populations and on their impact on parasitoids controlling Liriomyza species. The toxicity of these chemicals to L. huidobrensis and three common parasitoids (Hemiptarsenus varicornis Gerault, Opius sp., and Gronotoma micromorpha Perkins) was therefore evaluated in Indonesia with mortality laboratory assays. All three chemicals were effective against larvae of three populations of L. huidobrensis with different histories of chemical exposure. Dimehypo caused mortality in adult Opius sp., G. micromorpha, and H. varicornis, whereas abamectin was toxic only at concentrations substantially higher than the field rate. Cyromazine did not influence survival of the parasitoids. A commonly used fungicide, mancozeb, had no impact on parasitoid mortality. Trials were repeated with a strain of H. varicornis from Australia and a different parasitoid (Diglyphus isaea) recently found in Australia. Neither parasitoid was influenced by mancozeb or cyromazine. Abamectin applied at field rates caused some mortality among the adults of both species, but was less toxic than chlorpyrifos. Abamectin produced lower LC50s against Australian H. varicornis than against Indonesian H. varicornis. These results suggest that cyromazine can be incorporated into Liriomyza control programs in Indonesia that conserve parasitoids, whereas dimehypo and abamectin need to be used cautiously. Local Australian parasitoids should help control L. huidobrensis as long as only cyromazine and nontoxic fungicides are applied.

Topics: Agriculture; Animals; Australia; Diptera; Fungicides, Industrial; Hymenoptera; Indonesia; Insecticides; Ivermectin; Larva; Maneb; Pest Control, Biological; Triazines; Vegetables; Zineb

Mancozeb, a dithiocarbamate fungicide, was examined for its possible mutagenic activity using Salmonella typhimurium tester strains TA97a, TA98, TA100, and TA102. We found that Mancozeb exhibited toxic effects at the dose of 40 microg/plate and higher with all tester strains. Mancozeb showed dose-dependent increases in the number of revertants with and without metabolic activation when it was dissolved in DMSO or acetone with strain TA97a; however, the number of revertants at the highest dose was less than two-fold compared to control values. We postulate that the true mutagenic potential of Mancozeb may be masked by its toxic effect to the tester strain used.

Topics: Dose-Response Relationship, Drug; Fungicides, Industrial; Humans; Maneb; Mutagenicity Tests; Mutagens; Salmonella typhimurium; Zineb

Mancozeb, an ethylenebisdithiocarbamate (EBDC), was administered orally at a dose of 700 mg/kg body weight/day to female virgin rats for 5, 10, 20, and 30 days to examine the effect on ovarian follicular development. No significant change occurred in the number of estrous cycles and the duration of proestrus, estrus, and metestrus, but mancozeb treatment for 5 days significantly increased the duration of diestrus. Mancozeb treatment for 10 days significantly increased the number of estrous cycle and the duration of estrus, with a concomitant significant increase in diestrus, but no change in proestrus and metestrus. With mancozeb treatment for 20 and 30 days, the number of estrous cycles and duration of proestrus, estrus, and metestrus were significantly decreased, with a concomitant significant increase in the duration of diestrus. Exposure of rats to mancozeb for 5 days resulted in a significant decrease in stage II and the total number of healthy follicles but no change in atretic follicles. Mancozeb treatment for 10 days resulted in a significant decrease in stages I, II, and IV and in the total number of healthy follicles. A significant increase in atretic follicles was found in rats treated with mancozeb for 20 and 30 days. No significant change occurred in body and organ weights in any group, but the thyroid weight of 20 and 30 days mancozeb-treated rats was significantly increased. The level of protein in the ovary was significantly decreased, but no change was found in the uterus and liver of mancozeb-treated animals. The level of glycogen was significantly decreased in the ovary and the uterus with mancozeb treatment, but not in the liver. With mancozeb treatment, the levels of phospholipids and neutral lipids were significantly increased in the liver but significantly decreased in the uterus. The change in the biochemical constituents of ovary, uterus, and liver was duration dependent. The results of the study thus indicate a marked disruption of the estrous cycle, pathological changes in the gonads, and organ-specific biochemical changes in rats after exposure to mancozeb.

Topics: Administration, Oral; Animals; Diestrus; Female; Liver; Maneb; Organ Size; Ovarian Follicle; Ovary; Rats; Rats, Wistar; Uterus; Zineb

The degradation pattern of metalaxyl, mancozeb and its metabolite ethylenethiourea (ETU) residues indicated a close correspondence to first order exponential degradation kinetics in soils. Degradation of fungicides in soils was predominantly biological as well as chemical in nature. Slower degradation ofmetalaxyl was noticed in the soils and their half-life values were higher than mancozeb and ETU as evident by wide range of half-life values from 41.24 to 165.11 days. In case of metalaxyl, Hiriyur soil was found to be superior in degrading the metalaxyl. Lower persistence of mancozeb and ETU was observed in soils resulting in rapid rate of degradation at smaller half-life values as compared to metalaxyl indicating the faster degradation of mancozeb and ETU. In mancozeb applied soils, the ETU formation was increased up to 30 days of incubation and thereafter it declined. Amongsoils, degradation of either mancozeb or ETU is not influenced by soil types. However, mancozeb persistence was higher in Hiriyur soils than Chettalli and Bangalore soils.

Topics: Agriculture; Alanine; Biodegradation, Environmental; Ethylenethiourea; Fungicides, Industrial; Humans; Maneb; Soil Pollutants; Zineb

Topics: Adult; Agriculture; Female; Fruit; Fungicides, Industrial; Humans; Korea; Male; Maneb; Occupational Exposure; Zineb

The objective of the present study was to determine the degradation products of mancozeb and ethylenethiourea (ETU) and elucidate the possible degradation pathways in solution as a result of chemical oxidation using ozone and chlorine dioxide. This study was developed in a solution at 100 ppm of mancozeb and ETU concentration over the course of 60 min. Two different oxidizing agents used in this study were (1) ozone at 3 ppm and (2) chlorine dioxide at 20 ppm. Ozone was continuously provided throughout the course of the reaction. Degradation products were detected with high-resolution GC-MS. The total analysis time was 4 min per sample combined with rapid GC separation and time-of-flight mass spectrometry (TOFMS). Hydrolysis of mancozeb led to m/z 144 ion fragmentation, which is 5-imidazoledithiocarboxylic acid, as a major degradation product. ETU showed M(+) 102, which corresponds to its mass, indicating this compound was stable in distilled water and did not undergo hydrolysis during 60 min. The average retention times of mancozeb and ETU were approximately 181-189 and 210-230 s, respectively. Ozonation of mancozeb produced ETU as a major product. Treatment of ETU with ozone produced several degradation compounds. From prolonged ozonation, the CS(2) or CS group was removed. Overall, several byproducts identified were M(+) 60, M(+) 84, M(+) 163, M(+) 117, and M(+) 267 by ozone and M(+) 117, M(+) 86, and M(+) 163 by chlorine dioxide treatment. Several of these have been reported, but others have never been reported previously.

Topics: Chlorine Compounds; Ethylenethiourea; Gas Chromatography-Mass Spectrometry; Hydrogen-Ion Concentration; Kinetics; Maneb; Oxides; Ozone; Solutions; Zineb

Topics: Environment; Epidemiologic Studies; Fungicides, Industrial; Humans; Maneb; Occupational Exposure; Reproducibility of Results; Sister Chromatid Exchange; Thyroid Hormones; Thyroid Neoplasms; Zineb

The use of pesticides in field application involves the risk of poisoning wild animals. The reproduction period of pheasant takes place at the same time as the spraying time of pesticides, which justifies, that we evaluate in a point of the ecotoxicologic view the influence of the pesticide on progressive avian embryo. The most frequent technical way is injecting the exam stuffs to the some part of the embryonated eggs under the bird teratological trials. The advantage of this method is that it can be injected in a correct measured dose into the optional part of eggs. The disadvantage of this method is that it can't model properly the influence on the environment. If adverse effect of the embraced chemical substance on the embryo is experienced under the study, it will be necessary to use an immersion treatment. This procedure shows only the possible indirect influence of the pesticide on the embryo but it can suitably model its influence in plant protection practice. Treatment was done on day 12 of incubation. Applied concentration of heavy element (Cd sulphate) was 0.01% and the concentration of pesticide (Dithane M-45) was 0.2%. Evaluation was done on day 19 of incubation. Injection treatment: the simultaneous administration of Cd sulphate and the 80% mancozeb containing fungicide formulation on day 12 of incubation did not result in a significant decrease in the average body weight of embryos compared to neither the control nor the pesticide individually treated group. At the same time the body weight of embryos significantly decreased because of combined administration as compared to the Cd sulphate treated group. The embryo mortality and the incidence of developmental anomalies markedly increased after the simultaneous administration. Immersion treatment: the combined administration of Cd sulphate and the mancozeb containing fungicide formulation on day 12 of incubation did not result in a significant decrease in the average body mass of embryos compared to neither the control nor the individually treated groups. The number of embryo mortality was very high after the simultaneous administration. The incidence of developmental anomalies was sporadic.

Topics: Animals; Cadmium Compounds; Chick Embryo; Environmental Exposure; Fungicides, Industrial; Immersion; Injections; Maneb; Metals, Heavy; Pesticides; Sulfates; Toxicity Tests; Zineb

Cu-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45) were studied in pheasants after administration as single compounds or in combination. The test materials were injected directly into the air-chamber of eggs on day 12 of the hatching period and evaulation was carried out on day 23 of incubation. The pheasant embryos were examined for the following: rate of embryo mortality, body mass, type of developmental anomalies, light microscopic examination. After the administration of copper-sulphate on day 12 of incubation, the average body weight of pheasant embryos significantly did not decrease as compared to the control. The embryonic mortality was 68%. After the administration of a mancozeb containing fungicide formulation (Dithane M-45) on day 12 of incubation, the average body weight of embryos did not decrease as compared to the control. The embryonic mortality was 50%. After the individual administration of pesticide, the incidence of developmental anomalies was very high. After the combined administration of copper-sulphate and the 80% mancozeb containing fungicide formulation (Dithane M-45) on day 12 of incubation the embryonic mortality markedly increased. The rate of embryo mortality was 93%. We did not find any degenerative change in the liver tissue in either the control group or the treated groups by light microscopic examination. In summary, it can be established that the simultaneous administration of Cu-sulphate and mancozeb containing fungicide formulation caused high toxicity compared with the individual toxicity of test materials.

Topics: Animals; Birds; Copper Sulfate; Dose-Response Relationship, Drug; Drug Synergism; Embryo, Nonmammalian; Fungicides, Industrial; Hungary; Liver; Maneb; Mortality; Teratogens; Toxicity Tests; Zineb

Environmental pollution of metal modelled by cadmium-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on chicken embryos after administration as a single compounds or in combination. The test materials were injected into the air-chamber in a volume of 0.1 ml/egg on day 0 of incubation. The concentration of cadmium-sulphate was 0.01%. The applied concentration of Dithane M-45 fungicide was 0.2%. Evaluation was done on day 19 of the hatching period. The individual administration of cadmium-sulphate and the 80% mancozeb containing fungicide formulation did not cause a significant reduction in body weight as compared to the control data. Embryonic mortality increased at all individual treated groups and reached almost a 35% rate. After the individual administration of pesticide, the number of chicken embryos with developmental anomalies did not differ markedly from the control. After the combined administration of cadmium-sulphate and the 80% mancozeb containing fungicide formulation (Dithane M-45) on day 0 of the hatching period embryonic mortality markedly increased. 88% of the treated embryos were dead. Results from the combined administration of cadmium-sulphate and an 80% mancozeb containing fungicide formulation (Dithane M-45) caused higher embryomortality with respect to individual toxicity test of cadmium-sulphate and fungicide in our study.

Topics: Animals; Cadmium Compounds; Chick Embryo; Dose-Response Relationship, Drug; Drug Synergism; Environmental Pollution; Fungicides, Industrial; Maneb; Sulfates; Teratogens; Toxicity Tests; Zineb

Calcium hypochlorite (Ca(OCl)(2)) and chlorine dioxide (ClO(2)), common disinfecting and bleaching chemicals used in the food industry, are potent oxidizing agents. In this paper, the degradation effects of chlorine dioxide on mancozeb and ethylenethiourea (ETU) residues were investigated in a model system and compared with those of liquid chlorine, under various conditions such as differing concentration, pH, reaction time, and temperature. All samples were analyzed for residues by GLC and HPLC. Rate of mancozeb degradation was dependent on pH, with pH 4.6 being the most effective. Mancozeb residues decreased 40-100% with chlorine and chlorine dioxide treatments. ETU residue concentrations in mancozeb solutions were monitored over 60 min. Under controlled conditions, the ETU residue concentrations increased up to 15 min reaction time and then decreased in all three pH ranges. Treatment with both chlorine and chlorine dioxide at pH 4.6, yielded no ETU residues at both 10 and 21 degrees C. The results show that chlorine dioxide gives excellent degradation effects at lower concentrations than liquid chlorine.

Topics: Calcium Compounds; Chlorine; Chlorine Compounds; Chromatography, Gas; Chromatography, High Pressure Liquid; Ethylenethiourea; Food Industry; Fungicides, Industrial; Hydrogen-Ion Concentration; Hydrolysis; Kinetics; Maneb; Oxidation-Reduction; Oxides; Pesticide Residues; Solutions; Water; Zineb

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 microg/g creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.

Topics: Adult; Agriculture; Biomarkers; Clothing; Environmental Monitoring; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Male; Maneb; Occupational Exposure; Skin; Skin Absorption; Zineb

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.

Topics: Animals; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Male; Maneb; Organometallic Compounds; Pregnancy; Rats; Rats, Wistar; Reproduction; Zineb

Mancozeb, an ethylene-bis-dithiocarbamate (EBDC), has been one of the most commonly used fungicides in commercial use for several decades. Nevertheless, up to now, no adequate published experimental studies on the carcinogenicity of Mancozeb have been published. Because of the importance of the compound and of the number of people potentially exposed (workers engaged in the production and use of the fungicide, people living in agricultural areas where the compound is sprayed, and people consuming polluted products), a long-term experimental study of Mancozeb was begun at the Cancer Research Center of the Ramazzini Foundation. Groups of 150 male and female Sprague-Dawley rats, 8 weeks old at the start of the treatment, were administered Mancozeb at the concentration of 1000, 500, 100, 10, and 0 ppm in feed supplied ad libitum for 104 weeks. At the end of the treatment, animals were kept under controlled conditions until spontaneous death. Mancozeb caused an increase in (1) total malignant tumors, (2) malignant mammary tumors, (3) Zymbal gland and ear duct carcinomas, (4) hepatocarcinomas, (5) malignant tumors of the pancreas, (6) malignant tumors of the thyroid gland, (7) osteosarcomas of the bones of the head, and (8) hemolymphoreticular neoplasias. On the basis of these data, Mancozeb must be considered a multipotent carcinogenic agent.

Topics: Animals; Carcinogens; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Male; Maneb; Neoplasms, Experimental; Rats; Rats, Sprague-Dawley; Zineb

Environmental pollution of metal modelled by copper-sulphate and a 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on chicken embryos after administration as a single compounds or in combination. The test materials were injected into the air-chamber in a volume of 0.1 ml/egg on day 12 of incubation. The concentration of copper-sulphate was 0.01%. The applied concentration of Dithane M-45 fungicide formulation was 0.2%. Evaluation was done on day 19 of the hatching period. The combined administration of copper-sulphate and the fungicide formulation did not cause a significant reduction in body weight as compared to the control data and the results from individual toxicity study of the test materials. After the combined administration of copper-sulphate and the fungicide formulation the rate of embryomortality was 40%. The incidence of developmental anomalies were sporadic. Light microscopic findings exhibited a degenerative change in the liver tissue of combined administration group. Activities of GPT and GOT enzymes increased markedly in the combined administration group. In summary, it can be established that the interaction of copper-sulphate and an 80% mancozeb containing fungicide formulation (Dithane M-45) caused higher embryomortality with respect to the test of individual toxicity of copper-sulphate and fungicide in our study.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Chick Embryo; Copper Sulfate; Drug Synergism; Fungicides, Industrial; Maneb; Teratogens; Toxicity Tests; Zineb; Zygote

The preventive activity of 1:8 mixture of cymoxanil and mancozeb against Phytophthora infestans was higher than that of either the two single ingredients or the other nine mixtures. The synergistic interaction existed (synergy ratio 2.01) between the two at the mixing ratio of 1:8, whereas additive interaction (synergy ratios ranged from 0.73 to 1.34) existed at the mixing ratios ranging from 1:1 to 1:7, from 1:9 to 1:10, 1:8 was the optimal ratio. The preventive activity of 1:8 mixture was higher than the curative and the eradicative. In addition, the eradicative synergism of inhibiting sporangia production on lesions was stronger than the eradicative synergism of inhibiting lesion extension and suppressing infection of sporangia, and than the curative synergism of inhibiting lesion sporulation on detached potato leaflets.

Topics: Acetamides; Drug Synergism; Fungicides, Industrial; Maneb; Phytophthora; Solanum tuberosum; Zineb

Foliar sprays of potato plants with phosphonic acid (partially neutralised with potassium hydroxide to pH 6.4) substantially reduced infection of the tubers by Phytophthora infestans, the cause of late blight, in glasshouse and field experiments over a 4-year period. Healthy tubers of blight-susceptible cultivars removed from treated plants and artificially inoculated by spraying with sporangial/zoospore suspensions of P infestans did not develop disease symptoms, demonstrating that the phosphonate applications had directly reduced the susceptibility of tubers to infection, probably as a result of translocation into tuber tissue. In contrast, foliar application of fosetyl-aluminium did not significantly reduce tuber blight development following inoculation. Five to six sprays of partially neutralised phosphonic acid (2 kg ha-1) applied at 10-14 day intervals resulted in the least tuber infection, but such a treatment regime may not be economic. In trials where the effect of timing and rate of application of 2-4 kg phosphonic acid ha-1 was examined, a single treatment of 4 kg ha-1 applied mid- or late-season proved the most effective. A spray programme in which one or two applications of phosphonic acid are combined with use of a non-systemic or systemic fungicide to enhance foliar protection offers the possibility of controlling both foliage and tuber blight and could have a major impact in reducing overwinter survival of P infestans in tubers.

Topics: Biological Transport; Environment, Controlled; Fungicides, Industrial; Hydrogen-Ion Concentration; Hydroxides; Maneb; Organophosphonates; Organophosphorus Compounds; Phytophthora; Plant Leaves; Plant Stems; Potassium Compounds; Solanum tuberosum; Time Factors; Zineb

Cyazofamid (ISO proposed common name), 4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide is a novel fungicide exhibiting specific activity against diseases caused by Oomycetes. In tests, cyazofamid at 0.4-1.6 mg litre-1 exhibited excellent preventative activity against Phytophthora infestans on tomato and Pseudoperonospora cubensis on cucumber. Minimum inhibitory concentrations of cyazofamid against both diseases were over 63 times lower than those of mancozeb and at least 16 times lower than those of metalaxyl. Cyazofamid at 1.6-25 mg litre-1 exhibited not only preventative activity, but also stable residual activity and rainfastness. Cyazofamid at 6.3 mg litre-1 reduced zoosporangia formation of P infestans and P cubensis on host plants by 100 and 94% respectively. Cyazofamid also exhibited translaminar and curative activity. Cyazofamid has a new mode of action for fungicides and exhibits no cross-resistance with other currently registered and commonly used fungicides. These properties lead to a high level control by cyazofamid in field.

Topics: Alanine; Animals; Cucumis sativus; Dose-Response Relationship, Drug; Fungicides, Industrial; Imidazoles; Maneb; Microbial Sensitivity Tests; Molecular Structure; Oomycetes; Phytophthora; Solanum lycopersicum; Sulfonamides; Zineb

A simple and rapid method is presented for the analysis of residues of ethylenebis(dithiocarbamate) (maneb, zineb, and mancozeb) and N,N-dimethyldithiocarbamate (thiram and ziram) fungicides in dry tobacco leaves and peaches. Residues are extracted and hydrolyzed to CS(2) in a single step by use of microwave energy in a closed-vessel system while the evolved CS(2) trapped in a layer of iso-octane overlaying the reaction mixture is taken for gas chromatographic-flame photometric analysis. This combined extraction-hydrolysis step is carried out in 10 and 15 min for sets of 12 samples of tobacco and peach matrices, respectively. Total sample preparation time for GC analysis is 40 min. The limits of detection (LOD) are 0.005 mg/kg for thiram and ziram on peaches and 0.1 mg/kg for maneb, zineb, and mancozeb on tobacco. The respective LOD and limit of quantification (LOQ) levels in CS(2) equivalents are 0.003 and 0.006 mg/kg on peaches and 0.04 and 0.2 mg/kg on tobacco, respectively. Recoveries in the 0.01-60 mg/kg fortification range are 80-100% with respective relative standard deviations <20%. The method was used for the analysis of >3000 commercial tobacco samples including also different marketed cigarette brands.

Topics: Drug Stability; Food Contamination; Fungicides, Industrial; Hydrochloric Acid; Hydrolysis; Maneb; Microwaves; Nicotiana; Prunus; Quality Control; Sensitivity and Specificity; Thiocarbamates; Thiram; Zineb; Ziram

An in vitro bioassay for detection and quantitative assessment of chemicals with the capacity to disrupt adrenal steroidogenesis has been developed and used to compare the cytotoxic and endocrine-disrupting potential of four pesticides. Enzymatically dispersed adrenocortical cells of rainbow trout (Oncorhynchus mykiss) were exposed in vitro to atrazine, diazinon, endosulfan, and mancozeb, and cortisol secretion in response to ACTH or dibutyryl-cAMP (dbcAMP) and cell viability were determined. The effective concentration, EC50 (concentration that inhibits cortisol secretion by 50%), the median lethal concentration, LC50 (concentration that kills 50% of the cells), and the LC50/EC50 ratio were established for the test pesticides. The pesticides were ranked as follows: EC50, endosulfan < diazinon < mancozeb < atrazine; LC50, diazinon < endosulfan < mancozeb < atrazine, with diazinon as the most cytotoxic. Endosulfan and mancozeb disrupted sites downstream of the cAMP-generating step of the cortisol synthetic pathway while atrazine seemed to act upstream from the cAMP step. The in vitro adrenal bioassay can be used for screening of adrenotoxicants and for mechanistic studies of adrenotoxicity.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Atrazine; Bucladesine; Diazinon; Endosulfan; Fungicides, Industrial; Herbicides; Hydrocortisone; Insecticides; Maneb; Oncorhynchus mykiss; Receptors, Corticotropin; Zineb

Liquid chromatography/mass spectrometry (LC/MS) has been applied to analyze N,N'-ethylenebisdithiocarbamate fungicides (EBDCs: manzeb, maneb and zineb) in environmental water samples. The EBDCs that are zinc and/or manganese salts are transformed into readily water-soluble sodium salts by adding an alkaline EDTA solution. The N,N'-ethylenebisdithiocarbamate anion is extracted into chloroform-hexane (3:1) as an ion pair with tetrabutylammonium, and then S-alkylated with methyl iodide. The extraction and derivatization are carried out at room temperature. The derivatized ethylenebisdithiocarbamic acid dimethyl ester is introduced into an LC/MS equipped with a negative ion electrospray ionization interface. Identification of the compound is performed with the specific quasi-molecular ion, and the quantitative analyses are carried out using the peak areas. The average recoveries and coefficients of variation of EBDCs at sub-ppb level are 79.1% and 29.3% (n = 6), respectively. The limit of detection based on standard deviation of 0.043 microg/L for manzeb is achieved.

Topics: Calibration; Fresh Water; Fungicides, Industrial; Gas Chromatography-Mass Spectrometry; Maneb; Spectrometry, Mass, Electrospray Ionization; Water Supply; Zineb

Topics: Animals; Avoidance Learning; Dose-Response Relationship, Drug; Fungicides, Industrial; Lead; Maneb; Nitrates; Oligochaeta; Toxicity Tests; Zineb

Mancozeb, an organocarbamate fungicide, was administered to examine the effect on implantation at doses of 18, 24, 30 and 36 mg/kg body weight/d to normal virgin swiss albino mice for 8 days to pregnant mice. The vaginal smear and body weight of the mice were recorded daily and mice were sacrificed on 9th day of pregnancy. There was a complete inhibition of implantation in 36 mg mancozeb treated mice with 100% pre-implantation loss. There was a partial inhibition of implantation in 24 and 30 mg mancozeb treated mice with 53.44 and 90.16% pre-implantation loss respectively. However, implantation was not affected in 18 mg mancozeb treated mice with 4.92% pre-implantation loss when compared to oil treated controls. To study the temporal effect, the effective dose of 36 mg/kg body weight/d mancozeb was administered orally for 3 and 5 days and on day 3 only. There was a complete inhibition of implantation in 5 days treated mice with 100% pre-implantation loss and partial inhibition of implantation of 3 days treated mice with 75% pre-implantation loss. However, implantation was not affected in mice treated on day 3 only with 1.63% pre-implantation loss when compared to control mice. There was a significant decrease in the diestrus phase with the result there was a concomitant increase in the estrus phase and there was a significant decrease in the uterus weight with 24, 30 and 36 mg and for 3 and 5 days with 36 mg mancozeb treatment. Inhibition of implantation by mancozeb may be due to hormonal imbalance or its toxic effects.

Topics: Animals; Dose-Response Relationship, Drug; Embryo Implantation; Estrus; Female; Fungicides, Industrial; Maneb; Mice; Pregnancy; Zineb

During the extremely wet vegetation season in 1999 the efficiency of protection of two cultivars of field grown tomato (Lycopersicon lycopersicum (L.) Karsten), 'Pick Rite' and 'GO 101', against tomato late blight (Phytophthora infestans (Mont.) de Bary) using three ecologically acceptable growing techniques and agrochemical measures (growing on black plastic mulch with no fungicides used, spraying with Dithane M-45 (mancozeb), spraying with Cuprablau-Z (Cu-hydroxide) and control) have been studied. It was found out that under such extreme weather conditions none of these measures can ensure an adequate protection of tomato. The highest yield of healthy fruits (0.30 kg per plant) was obtained after a threefold spraying with Dithane M-45 (mancozeb), the highest percentage of non infected fruits (38.1%) after a twofold spraying with Cuprablau-Z (Cu-hydroxide). The black plastic mulch, used with the intention to reduce the plant contact with the potential inoculum in the soil proved to be ineffective.

Topics: Agriculture; Copper; Dose-Response Relationship, Drug; Fungicides, Industrial; Hydroxides; Maneb; Phytophthora; Rain; Slovenia; Solanum lycopersicum; Treatment Outcome; Zineb

The reproduction toxicity of lead acetate and 80% mancozeb containing fungicide formulation (Dithane M-45) were studied on rats. The lead acetate was applied in diet at the following dose groups: Control-1,000-5,000-10,000 mg/kg. Three treatment and a control groups were applied, 4,500 mg/kg Dithane M-45 was administered in all the dose levels simultaneously in diet. The basis of the method was the OECD Guideline for Testing of Chemicals No. 415. Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals diminished significantly before the pregnancy period. This tendency was also seen on males after the combination treatment. Remarkable body weight growth of female animals was observed during lactation period at the two high dose levels. Diminished body weight data of offsprings were measured after treatment at the end of the lactation period. The histological examination showed a general tubulonephrosis in the trial. Summing up, it can be established the administration of fungicide Dithane M-45 did not increase the toxicity of lead acetate.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Lead; Male; Maneb; Organometallic Compounds; Pregnancy; Rats; Rats, Wistar; Reproduction; Zineb

This article describes the outcome of laboratory experiments to determine the acute and sublethal effects of the fungicide mancozeb on the earthworm Eisenia fetida. Apart from a standardized acute test, young worms, 25 days old, were exposed to mancozeb mixed into a urine-free cattle manure substrate. Five groups of 10 worms each were used per concentration level (0, 8, 44 mg/kg substrate). The following life-history parameters were measured: growth in consecutive weeks over a 6-week period, survival rate, maturation time, cocoon production, hatching success of cocoons, number of hatchlings per cocoon, and incubation time of cocoons over another 4 weeks. The results indicated that mancozeb had no significant detrimental effect on either growth or reproduction of E. fetida at the recommended dose (8 mg/kg) or at an estimated environmental concentration (44 mg/kg). The findings do not support the hypothesis that avoidance response to mancozeb could serve as an indication of toxicity.

Topics: Animals; Behavior, Animal; Fungicides, Industrial; Growth; Hydrogen-Ion Concentration; Lethal Dose 50; Maneb; Oligochaeta; Reproduction; Zineb

We have previously shown that the dithiocarbamate fungicide, Mancozeb, strongly induces lacZ reporter expression from an endogenous heat-shock promoter (hsp16) in the PC72 transgenic strain of the nematode Caenorhabditis elegans. Such evidence of organismal stress, in a nontarget species at subapplication concentrations, was much less apparent for the related fungicide, Maneb, which only weakly induced reporter expression. We now show that reporter induction by Mancozeb is marginal (<60%) after a few hours' exposure, but increases substantially (to almost 10-fold) after overnight exposure. In conjunction with our previous results using intermediate exposure periods, this suggests that the factor limiting reporter responses is likely to be a slow rate of uptake and/or metabolism of the fungicide. We confirm that a potentially toxic metabolite of dithiocarbamate fungicides, namely ethylenethiourea (ETU), has minimal toxicity toward C. elegans, even after prolonged exposure at high concentrations. We demonstrate that exposure to Mancozeb (but not ETU) significantly inhibits larval growth in C. elegans, although this parameter is not markedly more sensitive than reporter induction as a toxicological endpoint. Finally, we have used two-dimensional electrophoresis to show that high concentrations of both Maneb and Mancozeb drastically simplify the protein spot profile compared with controls. However, only in the latter case is there evidence of novel proteins being induced. Both fungicides appear toxic to C. elegans, but only Mancozeb induces a strong heat-shock response.

Topics: Animals; beta-Galactosidase; Caenorhabditis elegans; Dose-Response Relationship, Drug; Electrophoresis, Gel, Two-Dimensional; Ethylenethiourea; Fungicides, Industrial; Heat-Shock Proteins; Heat-Shock Response; Larva; Maneb; Organisms, Genetically Modified; Soil; Zineb

We evaluated the effects of mancozeb (Dithane M4-5), a protective carbamate fungicide, on transplacental carcinogenesis in Swiss albino mice. Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, is reported to possess carcinogenic and cocarcinogenic activity in various tumor models. In the present study, pregnant Swiss albino mice were administered mancozeb intraperitoneally on the 14th day of gestation. The first filial generation (F1 progeny) was promoted with a well-known tumor promoter 12-o-tetradecanoyl phorbol-13-acetate (TPA). The results revealed a significantly high tumor incidence (72%) in the F1 progeny of the animals initiated with mancozeb or a well known carcinogen 7,12-dimethyl benzanthracene (DMBA) and promoted with TPA in comparison to animals that were either from mothers given only the vehicle (DMSO) and promoted with TPA in F1 progeny or not promoted with TPA in F1 progeny. No significantly higher tumor incidence was observed in any other experimental groups. These results suggest that mancozeb or its metabolites are capable of crossing the placental barrier and can exert DNA damage and tumor initiating consequences in the fetal cells that, after promotion with TPA, get converted into neoplastic cells.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Disease Models, Animal; Female; Fungicides, Industrial; Male; Maneb; Maternal Exposure; Maternal-Fetal Exchange; Mice; Pregnancy; Prenatal Exposure Delayed Effects; Skin Neoplasms; Tetradecanoylphorbol Acetate; Zineb

The objective of this study was to determine the effectiveness of chlorine, chlorine dioxide, ozone, and hydrogen peroxyacetic acid (HPA) treatments on the degradation of mancozeb and ethylenethiourea (ETU) in apples. This study was based on model experiments at neutral pH and temperature. Fresh apples were treated with two different levels of mancozeb (1 and 10 microg/mL). Several of the treatments were effective in reducing or removing mancozeb and ETU residues on spiked apples. Mancozeb residues decreased 56-99% with chlorine and 36-87% with chlorine dioxide treatments. ETU was completely degraded by 500 ppm of calcium hypochlorite and 10 ppm of chlorine dioxide at a 1 ppm spike level. However, at a 10 ppm spike level, the effectiveness of ETU degradation was lower than observed at 1 ppm level. Mancozeb residues decreased 56-97% with ozone treatment. At 1 and 3 ppm of ozone, no ETU residue was detected at 1 ppm of spiked mancozeb after both 3 and 30 min. HPA was also effective in degrading the mancozeb residues, with 44-99% reduction depending on treatment time and HPA concentrations. ETU was completely degraded at 500 ppm of HPA after 30 min of reaction time. These treatments indicated good potential for the removal of pesticide residues on fruit and in processed products.

Topics: Decontamination; Food Contamination; Food Handling; Fungicides, Industrial; Kinetics; Maneb; Pesticide Residues; Rosales; Zineb

Among the myriad of recent studies on endocrine-disrupting chemicals, relatively few involve thyroid disruption, and most of these address exposure/disruption during embryonic life. Of those involving adult vertebrates, the endpoints examined are thyroid measurements. Even though thyroid disruption could potentially interfere with energy metabolism and thermoregulation such that over-winter survival might be compromised, the possible energetic consequences of these thyroid perturbations have not been investigated. We assessed thyroid function and measured resting metabolic rates of cotton rats chronically exposed to the fungicides vinclozolin or mancozeb. In addition, we measured norepinephrine-induced nonshivering thermogenesis and cold-induced thermogenesis and then cold-acclimated the mancozeb animals. Although thyroid hormone concentrations generally decreased, this was compensated for by an increase in thyroxine turnover (vinclozolin study only) such that thyroxine utilization rate was not different. In addition, there was no difference between the treated and control animals in any of the metabolic parameters measured. It is concluded that wild rodents exposed to these compounds are not energetically compromised.

Topics: Animals; Basal Metabolism; Body Temperature Regulation; Female; Fungicides, Industrial; Male; Maneb; Oxazoles; Sigmodontinae; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Zineb

Mancozeb, a fungicide of ethylenebisdithiocarbamate group was orally administered at doses of 500, 600, 700 and 800 mg/kg body weight/day to normal virgin rats of Wistar strain for 30 days. The vaginal smear and body weight of the rats were recorded daily and rats were sacrificed on 31st day. Estrous cycle was effected by showing a significant decrease in the number of estrous cycle, duration of proestrus, estrus and metestrus with concomitant significant increase in the duration of diestrus in all the mancozeb treated groups when compared with controls. There were a significant decrease in the number of healthy follicles and a significant increase in the number of atretic follicles in all the mancozeb treated groups when compared with controls. The histologic observation of the ovary revealed the presence of less number of corpora lutea and the size of the ovary was also reduced in high doses of mancozeb treated rats. There was a significant increase in the thyroid weight in all the mancozeb treated rats except in 500 mg/kg/d. In rats treated with 500 mg/kg/d showed a significant increase in the level of total lipids in the liver. In rats treated with 600 mg/kg/d mancozeb showed a significant decrease in the levels of glycogen and total lipids in the uterus and total lipids in the liver. In rats treated with 700 mg/kg/d showed a significant decrease in the levels of protein in ovary, glycogen, total lipids, phospholipids and neutral lipids in the uterus and a significant increase in the levels of phospholipids, neutral lipids in the ovary and total lipids, phospholipids and neutral lipids in the liver. In rats treated with 800 mg/kg/d showed a significant decrease in the levels of protein and glycogen in the ovary and protein, glycogen, total lipids, phospholipids and neutral lipids in the uterus and a significant increase in the levels of total lipids, phospholipids and neutral lipids in the ovary and liver when compared with controls. These observed effect of mancozeb on the estrous cycle, follicles and biochemical constituents may be due to imbalance in the hormone or toxic effect.

Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Estrus; Female; Fungicides, Industrial; Genitalia, Female; Maneb; Ovarian Follicle; Ovary; Rats; Rats, Wistar; Zineb

Artificial rainfalls were used to determine the effect of the amount of the rainfall and the time interval between pesticide application and rainfall event, on folpet and mancozeb residues on grapes and vine leaves. Forty-five mm of rain were administered to the vineyard in different amounts (45; 30+15; 15+15+15 mm). Folpet showed good rainfastness on the grapes and on the leaves. A modest decrease was observed only in the experiments that had received 45 mm of rain at one go. Mancozeb showed a lower rainfastness, since a portion of the deposit was easily washed off also by a modest rainfall. The percentage of this portion was higher in the grapes (38%) than in the leaves (20%). The data obtained in these experiments show that, in the case of folpet, it is not necessary to repeat the treatment when it rains the day after, while it is recommendable to repeat it in the case of mancozeb.

Topics: Fungicides, Industrial; Maneb; Pesticide Residues; Phthalimides; Plant Leaves; Rain; Vitis; Zineb

Laboratory studies were conducted in a model system to determine the effects of ozone (1 and 3 ppm) and hydrogen peroxyacetic acid (HPA) (5 and 50 ppm) at pH 4.6, 7.0, and 10.7 and at 10 and 21 degrees C on the degradation of mancozeb in solution over a 30 min period. All samples were analyzed for residues by GLC and HPLC. Ozonation and HPA treatment were effective in degrading mancozeb in solution. Rate of mancozeb degradation was dependent on pH, with the fastest rate at pH 7.0. Ethylenethiourea (ETU) residue concentrations in the mancozeb solutions were monitored over 60 min. Under controlled conditions, the ETU residue concentrations increased during the 15 min reaction time and then decreased for all three pH values. At 3 ppm of ozone treatment, no ETU residues were detected at all three pH ranges after 15 min of reaction time. Degradation of ETU by HPA was greatest at pH 4.6, and no ETU residues remained after 5 min at either 5 or 50 ppm. The results showed that ozone and HPA gave excellent degradation of pesticide residues depending on pH and temperature. These experiments indicated the potential for the removal of pesticide residues on fruit and in processed products.

Topics: Ethylenethiourea; Fungicides, Industrial; Maneb; Ozone; Peracetic Acid; Solutions; Zineb

Topics: Animals; Bufonidae; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Embryonic Development; Endosulfan; Eye Abnormalities; Forelimb; Fungicides, Industrial; Hindlimb; Insecticides; Lethal Dose 50; Maneb; Pesticides; Ranidae; Species Specificity; Survival Analysis; Toxicity Tests; Zineb

Recent epidemiologic studies showed increased frequency of birth defects in pesticide applicators and general population of the Red River Valley, Minnesota. These studies further indicated that this crop growing area used more chlorophenoxy herbicides and fungicides than elsewhere in Minnesota. Based on frequency of use and known biology, certain herbicides, pesticide additives, fungicides, and mycotoxins are suspect agents. To define whether these agents affect developmental endpoints in vitro, 16 selected agrochemicals were examined using the MCF-7 breast cancer cell line. In the flow cytometric assay, cell proliferation in this estrogen-responsive cell line indicates xenobiotic-mediated estrogenic effects. Cell viability, morphology, ploidy, and apoptosis were incorporated in this assay. Data showed that the adjuvants X-77 and Activate Plus induced significant cell proliferation at 0.1 and 1 microg/ml. The commercial-grade herbicides 2,4-D LV4 and 2,4-D amine induced cell proliferation at 1 and 10 microg/ml. The reagent-grade 2,4-D products failed to induce proliferation over the same concentration range, suggesting that other ingredients in the commercial products, presumably adjuvants, could be a factor in these results. The fungicides triphenyltin and mancozeb induced apoptosis at concentrations of 4.1 microg/ml (10(-5) M) and 50 microg/ml, respectively. Triphenyltin also induced aneuploidy (C2/M arrest) at 0.41 microg/ml (10(-6) M). Data provide a mechanistic step to understanding human reproductive and developmental effects in populations exposed to these agrochemicals, and initiative to focusing limited resources for future in vivo animal developmental toxicity studies.

Topics: 2,4-Dichlorophenoxyacetic Acid; Agrochemicals; Apoptosis; Cell Division; Cell Line; Cell Survival; Congenital Abnormalities; Female; Flow Cytometry; Fungicides, Industrial; Glycine; Glyphosate; Herbicides; Humans; Male; Maneb; Minnesota; Organotin Compounds; Ploidies; Regression Analysis; Surface-Active Agents; Triazoles; Tumor Cells, Cultured; Zineb

The teratogenic effects of lead acetate (Trial 1) and the possible teratogenic effect of this compound administered in combination with a fungicide containing 80% mancozeb (Trial 2) were studied in rats. The test substances were administered by gavage on Days 6-15 of gestation. In Trial 1, five groups were treated with lead acetate administered at doses of 0.1, 0.5, 1.0, 10.0 and 1000.0 mg/kg body weight (bwkg), respectively. In Trial 2, lead acetate was applied at doses of 0.1, 10.0 and 1000.0 mg/bwkg, respectively. In the latter case the dose of the pesticide was 750 mg/bwkg in all treated groups. Lead acetate was not teratogenic after a single administration. Combined administration of lead acetate and mancozeb gave rise to the following toxic effects: average maternal weight decreased during pregnancy, the ratio of live fetuses decreased after the two lowest doses, and fetal mortality increased in the lowest and in the highest dose groups. The ratio of fetal resorption was higher in all the treated groups than in the control group. A significant decrease occurred in average fetal and placental weight in each treated group as compared to the control. Maternal toxicity was expressed in paralysis of the hindlimbs in the two lowest dose groups. Maternal mortality was between 16.7 and 23.3% at the three dose levels. Phocomelia and hernia cerebri occurred as characteristic fetal developmental anomalies in all the treated groups. It is concluded that the joint administration of lead acetate and a mancozeb-containing fungicide can cause maternal toxicity, embryotoxicity and characteristic teratogenic effects.

Topics: Abnormalities, Drug-Induced; Animals; Dose-Response Relationship, Drug; Drug Interactions; Female; Fungicides, Industrial; Maneb; Organometallic Compounds; Pregnancy; Rats; Rats, Wistar; Teratogens; Zineb

Dithiocarbamate compounds are widely used agricultural fungicides that display low acute toxicity in mammals and that may become neurotoxic after prolonged exposure. Mancozeb, among other dithiocarbamates tested, proved to be the most potent (Ki= 0.27 microM) at noncompetitively inhibiting the in vitro ATP-dependent uptake of [3H]glutamate in rat cortical vesicles. Furthermore, mancozeb partially (20%) inhibited the ATP-dependent uptake of [14C]methylamine, used as an index for the vesicular transmembrane proton gradient (DeltapH), and evoked its efflux from organelles previously incubated with the 3H-labeled marker. Meanwhile, the vesicular uptake of 36chloride- anions whose concentrations regulate the transmembrane potential gradient (DeltapsiSV) was not impaired. The dithiocarbamate effects on the vesicular transport of [3H]glutamate thus appeared to involve mainly the DeltapH gradient rather than the potential gradient. Dithiocarbamate metabolites, the potent neurotoxin carbon disulfide included, did not affect the uptake process, thus implying the relevance for inhibition of the persistence, if any, of parent compounds in the brain. The present novel and potent in vitro interferences of selected dithiocarbamate pesticides with the vesicular transport of glutamate, if representative of in vivo alterations, may play some role in the probably complex origin of dithiocarbamate neurotoxicity.

Topics: Adenosine Triphosphate; Animals; Biological Transport; Brain; Chlorides; Glutamic Acid; In Vitro Techniques; Male; Maneb; Methylamines; Pesticides; Rats; Rats, Sprague-Dawley; Rats, Wistar; Synaptic Vesicles; Thiocarbamates; Zineb

The dithiocarbamate fungicides maneb and mancozeb induce a short-term stress response in a transgenic Caenorhabditis elegans strain (PC72) carrying a reporter lacZ gene under the control of a homologous heat shock (hsp16) promoter. This response can be readily monitored as induced beta-galactosidase activity, either by in situ staining or by a quantitative fluorometric enzyme assay. Particularly strong responses are induced by mancozeb (three- to fivefold above controls at 500 microg mL(-1)), causing acute toxicity at concentrations comparable to those recommended for field application (2 mg mL(-1)). Although much of this fungicide is adsorbed by soil, sufficient (ca. 6%) enters the soil water compartment to cause mild stress in the transgenic worm assay. Among possible metabolites from mancozeb breakdown, neither Mn2+ nor ethylenethiourea (ETU) is particularly toxic even at 10% of the optimum mancozeb dosage. Stress responses to a range of other pesticides are also reported, and in several cases it is clear that a nontarget soil species (here, transgenic C. elegans) may be sensitive to low-level contamination.

Topics: Animals; beta-Galactosidase; Caenorhabditis elegans; Dimethyl Sulfoxide; Dose-Response Relationship, Drug; Fungicides, Industrial; Maneb; Manganese; Manganese Poisoning; Organisms, Genetically Modified; Soil; Stress, Physiological; Toxicity Tests; Zinc; Zineb

The sample decomposition of the carbon disulfide evolution method for the determination of dithiocarbamate residues was carried out in a closed vial in the presence of hexane. The evolved carbon disulfide was extracted by the organic solvent and injected in a flow system for its quantification as copper complex. The conditions for batch decomposition, flow injection determination, and association of both were investigated with sodium diethyldithiocarbamate as model substance. An one-channel flow system was employed where the carrier stream was the ethanolic ethylenediamine/copper solution. The determination range was of 0. 01-1.26 microg of CS(2), with a relative standard deviation of 0.06% (n = 10), with a sample throughput of 45 samples/h. The association of the batch decomposition with the flow system was carried out with the fungicide mancozeb and was applied to the analysis of its residue in potato, lettuce, cucumber, and green bean crops. The approach allowed the analysis of 11 samples in triplicate in 2 h, with recoveries between 85% and 92% and relative standard deviation about 2%.

Topics: Carbon Disulfide; Flow Injection Analysis; Fungicides, Industrial; Maneb; Pesticide Residues; Zineb

Mancozeb, an ethylenebisdithiocarbamate fungicide was administered orally to male rats at doses 0, 500, 1000 and 1500 mg/kg/day for 90, 180 and 360 days produced dose dependent signs of poisoning, loss in body weight gain and mortality. However the signs of toxicity and mortality were more pronounced initially at 0-90 days as compared to 90-360 days of treatment period. A significant increase in the relative weight of liver and slight decrease in the kidney weight were observed in animals exposed to mancozeb (1000 and 1500 mg/kg/day) for 180 and 360 days associated with pathomorphological changes in liver, brain and kidney. Mancozeb has produced significant enzymatic changes in the activities of aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) throughout the period of study in a dose dependent manner. The alterations in the activity of enzymes associated with pathomorphological changes suggest that the chronic exposure of mancozeb produced significant toxicological effects in rats.

Topics: Acetylcholinesterase; Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Brain; Fungicides, Industrial; Kidney; Liver; Male; Maneb; Rats; Zineb

The results of environmental (11 subjects) and biological (57 subjects) monitoring of exposure to mancozeb, ethylenethiourea (ETU), and dimethoate are reported for employees of a firm producing commercial formulations containing these active ingredients. Urinary excretion [GM(GSD)] of ETU (microg/g creatinine) and alkylphosphates [dimethylphosphate (DMP) + dimethylthiophosphate (DMTP) + dimethyldithiophosphate (DMDTP)] (nmol/g creatinine) was 65.3(4.8) and 419.2(2.1), respectively, for employees engaged in the formulation of a product containing 80% mancozeb (n = 9), 36.6(1.9) and 296.4(2.4) for those formulating a product containing 35% mancozeb (n = 9), 9.5(6.1) and 1022.4(3.0) for those engaged in plant maintenance and internal transport of materials (n = 6), 10.3(4.2) and 322.8(3.3) for those engaged in packaging the mancozeb formulations (n = 16), 4.4(3.3) and 2545.4(3.9) for those formulating a product containing 40% dimethoate (n = 11), and 3.0(2.7) and 871.7(3.3) for those bottling the same dimethoate formulation (n = 10). Air concentrations (microg/m3) ranged from 25.3 to 194.4 for dimethoate, from 0.2 to 1.3 for ETU, and from 139.9 to 949.0 for mancozeb. Urinary excretion of ETU and alkylphosphates showed a significant correlation with mancozeb (r2 = .971), and ETU (r2 = .858), and dimethoate (r2 = .955) contamination of the hands. Potential dose estimates showed that the potential respiratory doses of mancozeb and dimethoate accounted, on the average, for 38% of the total potential dose. The potential respiratory dose of ETU was 7% of the total potential dose. Total estimated absorption did not exceed the accepted daily dose (ADI) for ETU and mancozeb, but the ADI for dimethoate was exceeded. Serum and erythrocyte cholinesterase activities in workers formulating dimethoate products were not significantly different before and after exposure.

Topics: Adult; Carcinogens; Chemical Industry; Dimethoate; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Inhalation Exposure; Insecticides; Job Description; Male; Maneb; Middle Aged; Occupational Exposure; Zineb

The use of pesticides in agriculture has increased over the last decade. Their widespread, often uncontrolled use causes thousands of people to be daily exposed to environmental agricultural chemicals, resulting in acute and chronic health effects. At present there is a paucity of data on the potential adverse effects of exposure to low levels of mancozeb for prolonged periods. In order to investigate the effects of mancozeb exposure on pulmonary wildlife populations, tracheas and lungs of nine 1- to 7-yr-old nonmigratory pigeons raised near peach orchards and vineyards repeatedly sprayed with the fungicide were examined. The experimental situation allowed us to evaluate the long-term natural toxicity of mancozeb as a sentinel for human populations occupationally exposed to fungicides. The use of nonmigratory pigeons may serve as an important biological source from which helpful data may be obtained for assessing risks to human health and gaining new insight into pathogenetic mechanisms.

Topics: Animals; Columbidae; Electron Probe Microanalysis; Environmental Exposure; Epithelium; Fungicides, Industrial; Lung; Maneb; Microscopy, Electron, Scanning; Models, Biological; Sentinel Surveillance; Trachea; Zineb

We have previously shown that fungicide Mancozeb causes a 50% decrease in Bradyhizobium sp USDA 3187 growth rate and affects the bacteria-root symbiotic interaction. In order to elucidate the fungicide toxicity mechanism we determined the effects of Mancozeb on cell chemical composition, glutathione (GSH) content (molecule involved in the detoxification process), glutathione S-transferase (GST) activity and on polyamine, exopolysaccharides, capsular polysaccharides and lipopolysaccharides. Mancozeb produced biochemical alterations in membrane composition, polysaccharides and polyamines. In spite of the increment of GSH content and GST activity, they are not enough to prevent the growth diminution.

Topics: Bradyrhizobium; Fungicides, Industrial; Inactivation, Metabolic; Maneb; Zineb

Mancozeb-a fungicide of ethylenebisdithiocarbamate group was orally administered at doses of 500, 1,000 and 1,500 mg/kg body weight/day for 30, 90, 180 and 360 days. Signs of toxicity mortality pattern and loss in body weight were observed in dose dependent manner. However, signs of intoxication and mortality pattern were more pronounced till the exposure of 90 days. A significant increase in testes and decrease in epididymis weight were associated with degeneration in seminiferous and epididymal tubules with loss of sperms. The decrease in gonadal acid phosphatase (ACP), succinic dehydrogenase (SDH) and increase in alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activity were observed with increased serum cholesterol. Sialic acid and protein content of testis and epididymis were also decreased in dose dependent manner. The study has thus indicated marked biochemical and pathological changes in gonads of male rats after chronic exposure to mancozeb.

Topics: Animals; Epididymis; Fungicides, Industrial; Male; Maneb; Organ Size; Rats; Seminiferous Tubules; Testis; Zineb

Topics: Adult; Dermatitis, Allergic Contact; Drug Combinations; Facial Dermatoses; Forearm; Fungicides, Industrial; Humans; Insecticides; Male; Maneb; Neck; Organometallic Compounds; Organothiophosphorus Compounds; Pyridines; Zineb

Two types of reactions were observed on the alteration of Drosophila vitellogenesis by the four fungicides used in this study. Dithane M45 resulted in stimulation associated with egg retention. However, the other three fungicides (Benlate, Bouillie bordelaise and Euparène) resulted in inhibition to a varying degree. Although the inhibition was comparatively limited due to Benlate it induced an egg retention. The inhibition was very high due to Bouillie bordelaise and Euparène. With Bouillie bordelaise an egg retention occured together with the reduction of vitellogenesis and caused an increase in the rate of the follicle resorption. The latter depended on the duration of treatment. With Euparène, no egg retention was observed and the toxicity was only noticed on vitellogenesis.

Topics: Aniline Compounds; Animals; Benomyl; Copper Sulfate; Drosophila melanogaster; Female; Fungicides, Industrial; Maneb; Ovary; Vitellogenesis; Zineb

Dynamins are GTPases which support receptor-mediated endocytosis and bind to several tyrosine kinase receptor-associated proteins known to mediate cell proliferation and differentiation. We have recently established that dynamin expression correlates with normal neuronal (Torre et al., J. Biol. Chem., 269 (1994) 32411-32417) and acinar pancreatic cell differentiation (Cook et al., Mol. Biol. Cell, 6 (1995) 405a). To begin to understand the role of dynamin in neoplastic pancreatic cell differentiation, we have followed the expression of this protein by immunohistochemistry during the development of pancreatic tumors in a mancozeb-nitrosomethylurea (NMU)-based carcinogenesis model recently developed in our laboratory (Monis and Valentich, Carcinogenesis, 14 (1993) 929-933). After a single intraperitoneal injection (50 mg/g body wt) of this carcinogen, rats fed with mancozeb develop pancreatic focal acinar hyperplasia (FACH), dysplastic foci (DYF) displaying acinar-like and ductular-like structures, and ductular-like carcinoma in situ (CIS). After histochemical staining using a monoclonal anti-dynamin antibody, high levels of this protein are consistently observed in well-differentiated acinar tumors (FACH). In contrast, dynamin immunoreactivity is almost undetectable in more advanced lesions showing a ductular-like phenotype (ductular-like DYF and CIS). This change in the expression pattern of dynamin during the progression of acinar into ductular-like DYF and CIS lesions correlates with recent findings from our laboratory showing a differential expression pattern for dynamin in pancreatic cells during embryonic development, with ductular-like precursor cells expressing low levels of this protein. Based upon these results, we conclude that more advanced ductular-like neoplastic cells induced by the carcinogen NMU in rat pancreas behave phenotypically like pancreatic precursor cells in their pattern of expression for dynamin.

Topics: Animals; Blotting, Northern; Carcinogens; Cell Differentiation; Dynamins; Endocytosis; Female; Fungicides, Industrial; GTP Phosphohydrolases; Male; Maneb; Methylnitrosourea; Pancreatic Neoplasms; Rats; Rats, Wistar; Receptor Protein-Tyrosine Kinases; Signal Transduction; Zineb

The ameliorating effect of vitamin C (injected intraperitoneally) was evaluated against changes in sperm count and sperm head morphology in mice fed either 3, 6 or 1000 mg/kg body wt/day endosulfan, phosphamidon or mancozeb, respectively. The animals received aqueous preparations of the pesticides and/or vitamin C once daily for 35 consecutive days. All three pesticides, irrespective of their chemical nature, significantly decreased the sperm count, as well as increased the frequency of sperm with aberrant head morphology. Out of the three doses of vitamin C used the middle and higher ones (20 and 40 mg/kg body wt/day, respectively) afforded comparatively more significant amelioration. The lower dose (10 mg/kg body wt/day) of this vitamin (quantitatively equivalent to the human therapeutic dose according to body weight) was least efficacious in both the tests. However, amelioration was never up to the control level in any case. Vitamin C doses, when administered alone, did not produce any adverse effect on sperm count and sperm head morphology.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Drug Interactions; Endosulfan; Fungicides, Industrial; Humans; Insecticides; Male; Maneb; Mice; Mice, Inbred Strains; Mutagens; Pesticides; Phosphamidon; Sperm Count; Sperm Head; Spermatozoa; Zineb

We report a patient with occupational contact dermatitis due to sensitization to mancozeb and perhaps metiram used in a vineyard. Patch testing showed strong allergic patch test reactions to 2 of the commercially available preparations used (Dithane Ultra and Polyram WG). Further patch tests showed allergic patch test reactions to mancozeb (0.5 and 1% pet.), a weak reaction to metiram (1% pet.) as well as to 4 other fungicides of the dithiocarbamate group (maneb, nabam, propineb and zineb), which had never been used in the vineyard.

Topics: Adult; Aerosols; Agricultural Workers' Diseases; Cross Reactions; Dermatitis, Allergic Contact; Dermatitis, Occupational; Female; Fungicides, Industrial; Humans; Maneb; Patch Tests; Zineb

Agricultural exposure to the organomanganese fungicide MANEB (manganese-ethylene-bis-dithiocarbamate) may induce an extrapyramidal syndrome resembling parkinsonism. To evaluate the relative role of manganese (Mn) and ethylene-bis-dithiocarbamate (EBDTC) in the hazard of organomanganese fungicides, we studied the effects of MANCOZEB (Mn-Zinc-EBDTC) and ZINEB (Zinc-EBDTC) on serumless dissociated mesencephalic-striatal primary coculture. High affinity 3H-dopamine (DA) and 14C GABA uptakes as well as immunocytochemical staining of tyrosine hydroxylase (TH)-containing cells were used as specific functional markers of DA and GABA neuron viability. Both MANCOZEB and ZINEB, at 10 and 50 microM concentrations, dose dependently reduced DA and GABA viability parameters. These data suggest that EBDTC rather than Mn may be primarily responsible for the cytotoxicity of organomanganese fungicides on neuronal systems relevant to the pathophysiology of parkinsonism.

Topics: Animals; Coculture Techniques; Corpus Striatum; Culture Media, Serum-Free; Ethylenebis(dithiocarbamates); Fungicides, Industrial; Maneb; Mesencephalon; Rats; Zineb

Topics: Agrochemicals; Dermatitis, Occupational; Dermatitis, Photoallergic; Fungicides, Industrial; Humans; Male; Maneb; Middle Aged; Zineb

The effect of vitamin C on the genotoxicity of three pesticides (Endosulfan, Phosphamidon, Mancozeb) was monitored by screening meiotic (metaphase I) chromosomes in the primary spermatocytes of Swiss albino mice, Mus musculus. A dose-dependent amelioration by vitamin C was observed in the Phosphamidon-treated group where quadruple the therapeutic dose produced maximum amelioration. In Endosulfan- and Mancozeb-treated groups, no further amelioration was achieved beyond the double dose of vitamin C, and the damage frequency did not come down to the control level. The possible mechanism of this effect is discussed.

Topics: Animals; Ascorbic Acid; Chromosome Aberrations; Endosulfan; Male; Maneb; Meiosis; Mice; Mutagens; Pesticides; Phosphamidon; Spermatocytes; Zineb

The modulatory effect of higher doses of vitamin C (ascorbic acid) on the genotoxicity of the three pesticides (endosulfan, phosphamidon, and mancozeb) was assessed in the in vivo micronucleus test in Swiss albino mice. Concurrent administration of the vitamin in a dose (20 mg/kg bwt/day) equivalent to double the human therapeutic one, along with each of the three pesticides, was most effective as an antimutagen. The therapeutic dose (10 mg/kg bwt/day) was comparatively less so, and the quadruple (40 mg/kg bwt/day) of it did not show any further amelioration.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Dose-Response Relationship, Drug; Endosulfan; Female; Male; Maneb; Mice; Micronuclei, Chromosome-Defective; Micronucleus Tests; Pesticides; Phosphamidon; Zineb

Vitamin C, when administered concurrently with a pesticide (endosulfan, phosphamidon or mancozeb), could significantly decrease the frequency of pesticide-induced clastogenic and mitosis-disruptive changes in the bone marrow cells of young Swiss albino mice. Of the three doses (10, 20 or 40 mg/kg b.wt./day) of the vitamin, the one which is double the human therapeutic dose (20 mg/kg b.wt./day) was most effective as an antimutagen to be followed by 40 mg and 10 mg. None of these doses of vitamin C showed any genotoxicity of their own for the parameters studied here.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Bone Marrow Cells; Chromosome Aberrations; Endosulfan; Maneb; Mice; Mice, Inbred Strains; Mitosis; Mutagenesis; Phosphamidon; Zineb

Topics: Biological Transport; Ethylenethiourea; Fungicides, Industrial; Maneb; Plants; Zineb

Topics: Administration, Oral; Animals; Body Weight; Hyperplasia; Hypertrophy; Iodide Peroxidase; Male; Maneb; Organ Size; Rats; Thyroid Gland; Thyroxine; Zineb

The effect of po administration of 100 or 200 mg mancozeb/kg body weight for 7 consecutive days on microsomal mixed-function oxidase catalyzed xenobiotic metabolism was investigated in the livers of newborn weanling and adults rats. Mancozeb caused a dose-dependent inhibition in the activities of p-nitroanisole O-dealkylase and aniline hydroxylase, while the activities of aminopyrine N-demethylase and benzo(a)pyrene hydroxylase were unaffected in all the age groups. The inhibition of p-nitroanisole O-dealkylase and aniline hydroxylase, was remarkably higher in adult than in newborn and weanling rats. There was a concentration-dependent decrease in cytochrome P-450 and microsomal protein contents. This study indicates selective age-independent inhibition of hepatic monooxygenases following repeated mancozeb dosing.

Topics: Age Factors; Aminopyrine; Aniline Compounds; Animals; Anisoles; Benzo(a)pyrene; Cytochrome P-450 Enzyme System; Fungicides, Industrial; Male; Maneb; Methylation; Microsomes, Liver; Oxidoreductases; Rats; Rats, Wistar; Xenobiotics; Zineb

Rats were treated with a single i.p. injection of the carcinogen nitrosomethylurea (NMU, 50 mg/kg b.w.) at day three of age. The treatment induced hyperplastic and atypical acinar cell proliferation [focal acinar cell hyperplasia (FACH)]. In this investigation, NMU treated rats were fed AIN-76 diet containing mancozeb (MZ; 100 mg/kg diet), a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt, which is an agricultural fungicide.. Group one was treated with NMU plus MZ (MZ-NMU), group 2 received NMU alone (NMU), group 3 was fed MZ and saline injected (MZ-SAL) and group 4 was the saline injected control (SAL). Rats were killed at week 24 of age. In MZ-NMU group pancreas there were FACH, dysplastic foci (DYF) and carcinomas in situ (CIS). FACH were larger, coalescent and may show areas of undifferentiated cells (focus within focus). DYF contain proliferative acinar and ductular structures with loss of polarity but no malignant traits. CIS had medullary appearance or consisted of irregularly shaped acini and ducts in stromal framework. Cell had scant cytoplasm and large hyperchromatic, pleomorphic nuclei. DYF and CIS were not seen in MZ group pancreas. The MZ-NMU group had increased mitotic index and greater number of apoptotic cells. There was no pathologic change in MZ-SAL group. Our data indicated that MZ did not cause pancreatic cell proliferation in normal rats whereas it had distinct promoting and progressor effects on NMU initiated pancreatic cells. Thus, a two-stage protocol of pancreatic carcinogenesis was achieved. It is suggested that the NMU protocol may be useful for testing promoter, progressor or inhibitory effect of chemical and physical agents on cell proliferation and transformation of rat pancreas.

Topics: Animals; Animals, Newborn; Carcinogens; Carcinoma in Situ; Cell Nucleolus; Female; Fungicides, Industrial; Hyperplasia; Lactation; Maneb; Maternal-Fetal Exchange; Methylnitrosourea; Pancreas; Pancreatic Neoplasms; Pregnancy; Rats; Rats, Wistar; Reference Values; Zineb

Oral administration of mancozeb (100 or 200 mg/kg body weight) for 7 consecutive days caused an increase in glutathione S-transferase (GST) activity in the liver of newborn, weanling and adult rats. This observed increase in GST activity was higher in weanling than in newborn and adult rats. Evaluation of acute effects at 4 and 20 h following oral administration of 200 mg mancozeb/kg showed a marginal increase in the levels of GST in adult rat liver. However, there was competitive inhibition of GST by the fungicide in vitro.

Topics: Animals; Dinitrochlorobenzene; Glutathione Transferase; Liver; Male; Maneb; Rats; Rats, Wistar; Zineb

Topics: Carbon Disulfide; Fruit; Fungicides, Industrial; Greece; Kinetics; Maneb; Maximum Allowable Concentration; Pesticide Residues; Reproducibility of Results; Time Factors; Zineb

The effect of mancozeb, a fungicide, on mouse skin ornithine decarboxylase (ODC) activity and DNA synthesis was studied. ODC activity was induced after topical application of mancozeb and exhibited a peak level at 5 h. This ODC induction was dependent on the dose of mancozeb applied. Cycloheximide, an inhibitor of protein synthesis, inhibited the mancozeb-caused ODC induction, indicating the effect on enzyme protein synthesis. The rate of DNA synthesis was also increased by mancozeb, as indicated by increased [3H]thymidine incorporation into skin DNA. Induction of ODC activity and DNA synthesis are among the events probably involved in the tumorigenic action of mancozeb on mouse skin.

Topics: Animals; Cycloheximide; DNA; Female; Fungicides, Industrial; Maneb; Mice; Ornithine Decarboxylase; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Zineb

Aspergillus funiculosus was isolated from rotted banana fruits, whereas Alternaria tenuis and Fusarium sp. were isolated from rotted tomato fruits. The isolated fungi tolerated relatively high levels of the fungicide, Dithane, up to 2560 ppm on solid medium, but grew well at 40 ppm when supplemented with liquid medium. They are able to tolerate selenite up to 2% (w/v) sodium selenite. A. funiculosus showed no growth in the presence of mixture of 2.5 ppm selenium and 20 ppm Dithane, whereas Fusarium sp. failed to grow at 2.5 ppm selenium and 10 ppm Dithane, or at 10 ppm of each. Nevertheless, Alternaria tenuis is more tolerant; it showed growth in the presence of relatively high levels of selenium and Dithane; up to 10 ppm selenium and 40 ppm Dithane, however, its growth was inhibited by the presence of a mixture of both. The results suggested new form of highly active fungicides. Selenium as an essential nutrient at such very low concentrations, as well as the application of very low concentrations of the fungicide, would certainly reduce the hazardous effect of such pollutant in the environment.

Topics: Alternaria; Aspergillus; Carbohydrates; Drug Interactions; Fungal Proteins; Fungicides, Industrial; Fusarium; Lipids; Maneb; Selenium; Sodium Selenite; Zineb

A study on the persistence, residues and residue distribution of mancozeb in tomato plant-soil system, as well as effects of cooking on transformation of residual mancozeb were carried out with radiotracer technique. Half-life values for total mancozeb residues on tomato leaves and in soil were observed to be 9.5 and 7.6 days, respectively. The results also suggested that mancozeb residues in soil were readily uptaken by plants and leach to soil layer as deep as 28cm within two weeks, although over 90% of the residues remained in the upper layer (0-6cm) of the soil. Translocation of the residues of mancozeb, especially the water soluble metabolites including ETU, throughout the plants could be one of the factors responsible for the contamination of tomato fruits. Deposit of sprayed mancozeb on the fruit skin was another important factor leading to the contamination of fruits. Fruit skin contained higher levels of residues than the pulp. Washing with water could remove more than 50% of the residues on the skin. It was also found that 20-30% of the residual mancozeb degraded to ETU during cooking process. The tomatoes should be washed to reduce the residues of the fungicide and ETU in food.

Topics: Autoradiography; Carbon Radioisotopes; Fungicides, Industrial; Maneb; Pesticide Residues; Plants; Soil Pollutants; Zineb

Mancozeb, a commonly used fungicide, has been shown to induce tumours in mouse skin and maneb, unit constituent of mancozeb, is reported to induce tumours in rats. The mechanism by which mancozeb induced tumorigenicity is not known. Since the levels of inositol phospholipids and phosphatidic acid have roles in the regulation of cell proliferation, the effects of mancozeb on the levels of these lipids were studied in rats. Daily oral administration of commercial grade mancozeb at a concentration of 50 mg/kg body wt for 30 days (5 days a week) caused no significant change in the levels of inositol phospholipids and phosphatidic acid (PA) in both cerebrum and liver, while at high concentration (250 mg/kg body wt) under the same treatment schedule mancozeb increased the levels of these lipids. In cerebrum, the levels of phosphatidylinositol (PI) and PA were increased by 36 and 43% respectively without affecting the levels of polyphosphoinositides, whereas in liver the levels of not only PI (50%) and PA (49%) but also those of polyphosphoinositides were increased. These results show that mancozeb influences the levels of PA and inositol phospholipids, involved in phospholipase C-pathway of signalling.

Topics: Animals; Brain; Dose-Response Relationship, Drug; Female; Fungicides, Industrial; Liver; Maneb; Organ Size; Phosphatidic Acids; Pregnancy; Rats; Zineb

Comparative evaluation of the acute effects of ethylenebisdithiocarbamate (EBDC) fungicides, mancozeb and zineb on microsomal mixed function oxidases (MFO) revealed marked substrate-dependent inhibition of oxidative metabolism of aminopyrine, p-nitroanisole and aniline in rats sacrificed 4 hr after oral administration of 100 mg mancozeb or zineb/kg body weight. Mancozeb inhibited p-nitroanisole O-dealkylase and aniline hydroxylase to a greater degree than zineb, whereas the inhibition of aminopyrine N-demethylase by the two fungicides was quantitatively comparable. Interestingly, aryl hydrocarbon hydroxylase (AHH) which exhibited maximum inhibition with mancozeb, remained unaffected following zineb administration. The time-course and dose-dependence of MFO inhibition examined 1 and 4 hr after a single oral dose of 100 mg or 250 mg zineb/kg was expressed as a dose-dependent decline in the rate of xenobiotic biotransformation at 4 hr. In vitro interaction of zineb with MFO resulted in slightly greater inhibition of aminopyrine, p-nitroanisole and aniline while AHH exhibited more pronounced decrease with mancozeb. The magnitude of inhibition of aminopyrine N-demethylase and AHH was independent of the time of preincubation of fungicides with the enzyme. Kinetic studies indicated the non-competitive nature of AHH inhibition. Chronic oral treatment with mancozeb and zineb at a dose of 250 mg/kg for 4 weeks did not modify xenobiotic biotransformations except for a slight induction of aminopyrine N-demethylase by mancozeb.

Topics: Animals; In Vitro Techniques; Kinetics; Liver; Male; Maneb; Mixed Function Oxygenases; Oxidation-Reduction; Pesticides; Rats; Xenobiotics; Zineb

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cocarcinogenesis; Female; Fungicides, Industrial; Maneb; Mice; Skin Neoplasms; Thiocarbamates; Zineb

Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas.

Topics: Administration, Topical; Animals; Body Weight; Fungicides, Industrial; Maneb; Mice; Papilloma; Skin Neoplasms; Survival Analysis; Zineb

The present investigation reports the effect of chronic oral administration of mancozeb, a fungicide, on hepatic microsomal carboxylesterases/amidases or B-esterases responsible for hydrolytic metabolism of aspirin (acetylsalicylic acid or ASA) at pH 5.5 and 7.4, 2-acetylaminofluorene (AAF), acetanilide and p-nitrophenylacetate (NPA) and cholinesterase in rat. Oral administration of mancozeb (250 mg/kg/day) for 30 days caused significant stimulation of ASA esterase I (pH 5.5), ASA esterase II (pH 7.4), AAF N-deacetylase and acetanilide N-deacetylase in liver. However, the activities of NPA esterase and cholinesterase remained unaffected. Evaluation of induction kinetics demonstrated that the pattern and magnitude of responses of these microsomal hydrolases to mancozeb treatment for 7 days were comparable to those obtained after treatment for 30 days. The activities of hydrolases were not altered in animals killed 4 hr after an oral dose of mancozeb. Mancozeb did not affect these hydrolases in vitro.

Topics: 2-Acetylaminofluorene; Acetanilides; Animals; Aspirin; Fungicides, Industrial; Hydrolases; Male; Maneb; Microsomes, Liver; Nitrophenols; Rats; Xenobiotics; Zineb

Exposure of workers to ethylenebisdithiocarbamates (EBDCs; maneb or mancozeb) in 29 potato farms was evaluated during the control of potato late blight. Concentrations of EBDCs and ethylenethiourea (ETU), an impurity and degradation product in EBDC formulations, in ambient air were evaluated during pesticide application. Biological monitoring of exposure to EBDCs was carried out by measuring the concentrations of ETU, a metabolite of EBDCs, in urine for 22 days after the end of the exposure. The estimated inhaled doses of ETU and EBDCs during the average four hour application period were 0.07 and 1.8 micrograms/kg, respectively. Only 1-10% of ETU on the clothes reached the skin. The creatinine corrected concentrations of ETU in urine were 0.1-2.5 micrograms/mmol creatinine 24 hours after exposure ended. The estimated half life for eliminating ETU through the kidneys was close to 100 hours. These results indicate that the measurement of ETU in urine is suitable for biological monitoring of exposure to EBDCs.

Topics: Agriculture; Air Pollutants, Occupational; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Ethylenethiourea; Humans; Imidazoles; Male; Maneb; Protective Clothing; Thiocarbamates; Zineb

It has been found that Phytophthora cactorum mainly infects ginseng roots and causes phytophthora roots rot without symptoms on the leaves. The results of fungistatic test indicate that mycelial growth of the pathogen can be inhibited completely by Mancozeb and Metalaxyl at 100 ppm in vitro.

Topics: Alanine; Maneb; Panax; Plant Diseases; Plants, Medicinal; Zineb

Ethylenethiourea (ETU) is a ubiquitous impurity of the ethylenebisdithiocarbamate (EBDC) fungicides widely used in agriculture and forestry. In the present study, ETU was used as a measure of the exposure to EBDC on potato farms and in pine nurseries during the application of EBDC fungicides and the weeding of the sprayed vegetation. Biological and hygienic monitoring was carried out through the analysis of ETU in the breathing zone and the urine of exposed workers. Even if the concentrations of ETU in the ambient air of pine nurseries exceeded those of potato farms, the concentrations of ETU in the urine of potato farmers exceeded those of pine nursery workers. This result may have been due better protective equipment in the pine nurseries. The excretion rate was 6-10 ng/h during the first 60 h after the cessation of exposure, and it diminished thereafter to 0.2 ng/h over a 22-d observation period.

Topics: Adult; Air Pollutants; Breath Tests; Environmental Exposure; Ethylenethiourea; Evaluation Studies as Topic; Female; Humans; Imidazoles; Male; Maneb; Risk Factors; Thiocarbamates; Thyroid Diseases; Urine; Zineb

The estrogenic effect of the ethylenebisdithiocarbamate fungicide Novozír MN 80 (Duslo, Sal') was studied by means of the screening method determining the reproductive risk of chemical substances, recommended by the Environmental Protection Agency. Compared to intact controls, a significant increase in relative uterine weight was recorded in the group of animals which received 1/25 of the maximal tolerable concentration of Novozír MN 80. Compared to negative controls (Tween 80), the relative uterine weight was increased significantly after administration of 1/25 and 1/50 of the maximal tolerable concentration of Novozír MN 80. On histologic examination the cuboidal epithelium of the mucous membrane was found to be changed into columnar epithelium, with uneven distribution of enlarged nuclei in the vacuolized cytoplasm. At 1/25 maximal tolerable concentration thickening of the uterine wall was observed.

Topics: Animals; Animals, Newborn; Estrogens; Female; Fungicides, Industrial; Maneb; Organ Size; Rats; Rats, Inbred Strains; Thiocarbamates; Uterus; Zineb

The cytotoxic and mutagenic effects of the fungicides mancozeb and thiram were studied using human peripheral blood lymphocytes cultured in vitro with or without an S-9 mix microsomal metabolizing system. The results obtained suggested that the chemicals caused dose-dependent inhibition of thymidine uptake and unscheduled DNA synthesis on both resting and proliferating lymphocytes in the absence of the S-9 mix. In the presence of the S-9 mix, only thiram showed mutagenic activity by eliciting unscheduled DNA synthesis and a significantly higher frequency of sister chromatid exchanges than did controls.

Topics: Cell Survival; Cells, Cultured; DNA Damage; DNA Replication; Humans; Lymphocytes; Maneb; Mutagens; Sister Chromatid Exchange; Thiocarbamates; Thiram; Zineb

Topics: Agricultural Workers' Diseases; Air; Chromatography, High Pressure Liquid; Ethylenethiourea; Fungicides, Industrial; Humans; Imidazoles; Maneb; Occupational Diseases; Spectrophotometry, Atomic; Spectrophotometry, Ultraviolet; Thiocarbamates; Zineb

The effect of two herbicides (paraquat and 2,4-dichlorophenoxybutyric acid) and two fungicides (mancozeb and captafol) was studied on the growth of Flagellospora penicillioides, Lunulospora curvula and Phalangispora constricta using the poisoned-food technique. The pesticides did not produce any inhibition of growth at concentrations up to 5 mg/l. The required concentration to bring about total inhibition of growth varied among the chemicals and the cultures. The herbicides produced a slight enhancement of culture growth at concentrations ranging from 1 to 25 mg/l.

Topics: Captan; Cyclohexenes; Maneb; Mitosporic Fungi; Paraquat; Pesticides; Water Microbiology; Zineb

Chromosome aberrations and sister-chromatid exchanges (SCEs) were analyzed in short-term cultures of peripheral lymphocytes of 44 workers occupationally exposed to mancozeb during the production of the pesticide Novozir Mn80 and 30 control persons. The results suggest that mancozeb exposure was associated with a significant increase in the frequencies of cells with structural chromosome aberrations (2.07% vs. 1.10% in the controls), and the number of SCEs per cell (9.19 +/- 1.81 vs. 7.82 +/- 1.04 in the controls).

Topics: Adult; Chromosome Aberrations; Environmental Exposure; Female; Fungicides, Industrial; Humans; Lymphocytes; Male; Maneb; Sister Chromatid Exchange; Smoking; Thiocarbamates; Zineb

In this study the tumour-promoting activity of a carbamate fungicide, mancozeb, has been observed following topical application on mouse skin in a two-stage initiation--promotion protocol for carcinogenesis. Female Swiss albino mice were initiated with a single subcarcinogenic dose (52 micrograms) of 7,12-dimethylbenz[a]anthracene painted on the interscapular region. Seven days after initiation the mice underwent topical application of mancozeb (100 mg/kg body wt) three times per week as promoter. Development of tumours was observed after 12 weeks of mancozeb application in 1/14 animals and 100% tumorigenesis was recorded after 17 weeks of mancozeb application. On histological examination, these tumours were found mostly to be benign in nature, e.g. squamous cell papillomas and keratocanthomas.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cocarcinogenesis; Female; Fungicides, Industrial; Maneb; Mice; Skin Neoplasms; Thiocarbamates; Zineb

Topics: Animals; Insecticides; Male; Maneb; Mice; Mice, Inbred ICR; Organ Size; Phosmet; Sperm Count; Spermatozoa; Testis; Thiocarbamates; Zineb

The effects of Mancozeb and Zineb, two dithiocarbamate fungicides used to protect vegetables, on rat thyroid and liver function were studied in an acute and a chronic trial. These compounds may be spontaneously or metabolically transformed to ethylene thiourea, a goitrogenic, mutagenic and teratogenic molecule. Sex linked differences in sensitivity and the possibility that toxicity might be potentiated through induction of the microsomal drug metabolising system by phenobarbitone were investigated. When compared with the findings of Ugazio et al. (1985) on the toxicity of ethylene thiourea, the results obtained in this study, bearing in mind the doses employed and the fact that no potentiation by phenobarbitone was observed, suggest that the risks associated with exposure to these two fungicides are less severe than had been supposed.

Topics: Animals; Body Weight; Drug Synergism; Female; Liver; Male; Maneb; Phenobarbital; Rats; Rats, Inbred Strains; Sex Factors; Thiocarbamates; Thyroid Gland; Thyroxine; Triglycerides; Triiodothyronine; Zineb

Residues of EBDC (ethylenebisdithiocarbamate) fungicides and ETU (ethylenethiourea; 2-imidazolidinethione) were monitored in beers and wines from different locations. No EBDC residues were detected in any of the samples examined. Concerning the ETU residues, the residue levels higher than the limit of method detection (0.01 ppm) were 22.6% and 7.3% in the commercial beer and wine samples respectively, but the number of samples containing more than 0.1 ppm of ETU was practically negligeable.

Topics: Beer; Chromatography, Gas; Ethylenebis(dithiocarbamates); Ethylenethiourea; Fungicides, Industrial; Gas Chromatography-Mass Spectrometry; Imidazoles; Maneb; Pesticide Residues; Thiocarbamates; Wine; Zineb

Microorganisms which isolated from the plasters of prefabricated houses, constructed by Yübetaş company in Oran Ankara Were examined. As a result of isolations, Alternaria, Penicillium and Stemphylium species of fungi were founded on the plasters. The growth of the fungi was tested on Agrisan megess and Dyo Sadosan make plastic wall paints and it was found that these fungi showed a profuse growth in the former make paint, but not in the second one. When mancozeb (Dithan-M-45) in 0.2% and copper oxychloride (Mavi Bakir Sandoz) in 0.5% were added to the plaster the growth of the fungi were completely prevented, but Wettable powder sulfur in 0.4% did not prevent their growth but stimulated it.

Topics: Alternaria; Construction Materials; Copper; Housing; Maneb; Mitosporic Fungi; Paint; Penicillium; Zineb

Mancozeb is a protectant fungicide and is a polymeric complex of ethylene bis(dithiocarbamate)manganese (i.e. Maneb) with zinc salt. In this study, the tumour initiating ability of mancozeb has been observed by a 2-stage initiation-promotion protocol in mouse skin.

Topics: Animals; Carcinogens; Female; Maneb; Mice; Papilloma; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thiocarbamates; Zineb

Crl:CD rats were exposed (whole body) to mancozeb by inhalation at 0, 1, 17, 55, 110, 890, or 1890/500 mg/m3 for 6 hr/day from Day 6 through 15 of gestation (sperm-positive vaginal smear considered Day 1). Dams were killed 1 day prior to natural delivery and fetuses were examined externally, viscerally, and skeletally for any alterations. Maternal toxicity, as evidenced by significantly decreased body weight gain, hindlimb paralysis, general debilitation, and death or termination in extremis, was noted among rats exposed to mancozeb at concentrations of 500 to 1890 mg/m3. Dams from the 55 and 110 mg/m3 groups exhibited decreased body weight gain and hindlimb weakness. There was no maternal toxicity for dams exposed at a concentration of 17 mg/m3. Embryofetal toxicity, as evidenced by a significantly increased incidence of totally resorbed litters, external hemorrhage, and wavy ribs, was noted at concentrations of 55 mg/m3 and above. The embryofetal toxicity occurred only at concentrations toxic to the dam. Among the groups exposed to mancozeb, the incidence of major malformations was not dose related. Hence, under the test conditions of this study, mancozeb was not found to be teratogenic and produced no toxicity unique to the conceptus.

Topics: Abnormalities, Drug-Induced; Animals; Atmosphere Exposure Chambers; Body Weight; Female; Fetal Resorption; Fetus; Maneb; Maternal-Fetal Exchange; Particle Size; Pregnancy; Rats; Teratogens; Zineb

Topics: Aged; Dermatitis, Occupational; Humans; Male; Maneb; Thiocarbamates; Vitiligo; Zineb

This paper reports the effects of three commercial powders mixed into the diet, Dithane M-45 (mancozeb 80%), Pomarsol (thiram 80%) and Peltar (maneb 50% and methyltiophanate 25%) on survivorship of adults Drosophila and on the progeny. With wild-type adults (Oregon), fungicides were added to the diet at the rate recommended on the label. The mean lifespan was reduced by 42.5% (Pomarsol), 50% (Dithane M-45), and 83% (Peltar). For larvae of two strains (Oregon and triploid) intoxicated with Dithane M-45 and Peltar, a linear relationship was demonstrated between the doses and the percentage of the progeny reduction. The calculated doses inducing a 50% reduced progeny (PR50) are in the range of 400 to 700 ppm. With Pomarsol in the range of 500 to 1500 ppm and for the both strains, the progeny was decreased by about 60%. A very reduced size and a leg paralysis was observed with each toxic powder for Oregon and triploid flies. It appears that a triploid stock of chromosomes does not significantly modify the reaction of the flies.

Topics: Animals; Carbamates; Dose-Response Relationship, Drug; Drosophila melanogaster; Female; Fungicides, Industrial; Longevity; Male; Maneb; Reproduction; Thiram; Zineb

Topics: Ethylenebis(dithiocarbamates); Food Contamination; Fruit; Fungicides, Industrial; Maneb; Pesticide Residues; Thiocarbamates; Vegetables; Zineb

Topics: Acetamides; Animals; Bone Marrow; Chromosome Aberrations; Dose-Response Relationship, Drug; Humans; Lymphocytes; Maneb; Rats; Rats, Inbred Strains; Thiocarbamates; Zineb

A case of allergic contact dermatitis to the rubber additive material ethylene thiourea (ETU) is presented. Testing for cross-sensitivity gave a positive reaction to the fungicide Maneb, manganous ethylenebisdithiocarbamate, but this reaction was probably due to ETU which was detected in Maneb by thin-layer chromatography. Different sources of ETU are reported.

Topics: Dermatitis, Contact; Ethylenethiourea; Female; Humans; Imidazoles; Maneb; Middle Aged; Patch Tests; Rubber; Zineb

Topics: Dermatitis, Atopic; Dermatitis, Occupational; Fungicides, Industrial; Humans; Male; Maneb; Middle Aged; Thiocarbamates; Zinc; Zineb

Topics: Edible Grain; Ethylenethiourea; Hordeum; Hot Temperature; Imidazoles; Maneb; Pesticide Residues; Thiocarbamates; Triticum; Zinc; Zineb

35S-cysteine incorporation in the protein synthesis of liver and testes is studied in groups of 20 white rats each, following 14--day poisoning with dithiocarbamates, at doses 1/5 LD50, as follows: group one, cineb - o,180 g/kg, maneb - 0,140 g/kg, and mankozeb - 0,260 g/kg. Protein incorporation in liver and testes is studied after decapitation of the animals, within two hours of intraperitoneal 35S-cysteine injection at dose 15 micro C per rat. Liver and testes undergo appropriate treatment after the method of Munro et al./10/, as modified by Sheitanov /9/, and counting is done with VAZ--310. The results point to a varying degree of cysteine incorporation increase in the protein synthesis of liver and testes. It is attributed to a variety of dystrophic and necrobiotic changes in the tissues of either of the organs, taking place under the effect of dithiocarbamate preparations. An enhancement of regenerative processes in the above mentioned organs, associated with intensified protein synthesis, is by no means ruled out. Differences established in the intensity of amino acid incorporation correlate with the degree of protein synthesis disorders, mostly in terms of the effect of maneb preparations.

Topics: Acute Disease; Administration, Oral; Animals; Cysteine; Liver; Male; Maneb; Protein Biosynthesis; Rats; Sulfur Radioisotopes; Testis; Thiocarbamates; Zinc; Zineb

Oral administration of high dosages of the dithiocarbamate pesticides maneb and mancozeb was teratogenic in rats but not in mice. The malformations, severe limb and craniofacial defects, were pronounced after maneb treatment but less so after mancozeb and propineb, zinc-containing compounds. The teratogenic effect of maneb was progressively reduced by simultaneously administering increasing amounts of zinc acetate. The mechanism of the teratogenic effect may involve the compounds being chelating agents, trapping zinc required for many important enzyme systems.

Topics: Abnormalities, Drug-Induced; Acetates; Animals; Female; Fetal Resorption; Maneb; Mice; Pregnancy; Rats; Thiocarbamates; Zinc; Zineb