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Chemosphere Feb 2023Dithiocarbamate Fungicides (DTFs) are widely analyzed and studied mainly due to the fact that they play an important role in the cultivation of fruits and vegetables.... (Review)
Review
Dithiocarbamate Fungicides (DTFs) are widely analyzed and studied mainly due to the fact that they play an important role in the cultivation of fruits and vegetables. This manuscript aims to display the results of a bibliometric analysis based on the Web of Science© database, performed in the DTF and food research area. A total of 374 publications were examined. The most scientific production was concentrated between 2012 and 2021, showing a decrease of 32% over the last two years. The Journal of Agricultural and Food Chemistry, India, and Sardar Vallabhbhai National Institute of Technology were the most productive journal, country, and institution, respectively. Reference Publication Year Spectroscopy index showed a decrease of 95% in the last last years studied. Finally, current and future trends should focus on keywords such as individual DTF (Mancozeb, Thiram and Maneb), metabolites (Ethylenethiourea, Propilenthiourea) and a change in the analysis methodology: HPLC versus traditional GC.
Topics: Fungicides, Industrial; Thiram; Vegetables; Fruit; Bibliometrics
PubMed: 36435325
DOI: 10.1016/j.chemosphere.2022.137342 -
European Journal of Cancer Prevention :... Jan 2022The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been...
INTRODUCTION
The thyroid peroxidase inhibiting compounds methimazole, methylthiouracil, propylthiouracil, thiouracil (i.e. 'antithyroid' drugs) and ethylenethiourea have been associated to thyroid tumours in rodents. According to a systematic review by the International Agency for Research on Cancer (IARC) published in 2000, evidence for the human carcinogenicity was inadequate.
METHODS
We performed an up-to-date systematic review of human epidemiological studies on the association between such compounds and thyroid cancer incidence or mortality.
RESULTS
The literature research (1999-March 2020) identified four relevant articles. Considering also reports from the previous IARC review, this systematic review considered seven reports (five distinct studies) on antithyroid drugs and two on ethylenethiourea. As for antithyroid drugs, three reports based on different follow-ups gave results from a cohort of patients treated for hyperthyroidism in 1946-1964. In the earlier report, thyroid cancer incidence was higher in patients primarily treated with antithyroid drugs (3.2/1000) than in those originally treated with thyroidectomy (0.34/1000) or radioactive iodine (0.88/1000), which can be explained by the higher frequency of subsequent thyroidectomy, and hence the higher chance of cancer detection, in that group (30 vs. 0.5 and 1.2%). The two subsequent reports found no deaths from thyroid cancer among patients treated exclusively with antithyroid drugs through 1990 and 2014. A nested case-control study found an odds ratio (OR) of thyroid cancer of 2.79 [95% confidence interval (CI), 0.78-10.02, from a 2-year lag analysis] for ≥3 vs. no propylthiouracil prescriptions. The increased risk can be attributed to advanced diagnosis of an underlying cancer, as suggested by the stronger association observed in a no-lag analysis (OR, 8.03). In a historical cohort of newly diagnosed hyperthyroid patients, the hazard ratio for treatment with radioactive iodine vs. thionamides only was 0.45 (95% CI, 0.21-0.99), possibly due to the closer surveillance of patients receiving thionamides only. Two case-control studies did not find any association with the use of antithyroid drugs. As for ethylenethiourea, no thyroid cancer cases were found in a historical cohort of 1929 workers occupationally exposed in a 15-year period and no association with proxies of mancozeb exposure (a fungicide whose main metabolite is ethylenethiourea) was detected in a cohort of >236 000 farmers.
CONCLUSION
There is no evidence for a relevant role of either antithyroid drugs or ethylenethiourea on thyroid cancer.
Topics: Antithyroid Agents; Case-Control Studies; Ethylenethiourea; Humans; Hyperthyroidism; Iodine Radioisotopes; Propylthiouracil; Thyroid Neoplasms
PubMed: 33492873
DOI: 10.1097/CEJ.0000000000000658 -
Environmental Health Perspectives Jun 1995Humans are exposed to ethylenebisdithiocarbamates (EBDCs) from environmental sources. Exposure to EBDCs is chronic for workers in a variety of industries, where EBDCs... (Review)
Review
Humans are exposed to ethylenebisdithiocarbamates (EBDCs) from environmental sources. Exposure to EBDCs is chronic for workers in a variety of industries, where EBDCs are used for their properties as slimicides, vulcanization accelerators, antioxidants, and scavengers in waste-water treatment. EBDCs, and particularly the EBDC metabolite ethylenethiourea, have clearly defined, important toxic effects in various animal species, and there is reason to suspect they are carcinogenic in humans. In the absence of definitive information regarding human risk, further studies need to be done. In the interim, regular surveillance of workers with high levels of exposure to EBDCs, with specific attention to markers of thyroid and hepatic pathology, should be considered.
Topics: Animals; Antifungal Agents; Environmental Health; Ethylenebis(dithiocarbamates); Ethylenethiourea; Food Contamination; Hazardous Substances; Humans; Kinetics
PubMed: 7556009
DOI: 10.1289/ehp.95103568 -
Environmental Research Apr 2022Human serum and urine samples were analyzed for a suite of nitrosatable pesticides and potentially carcinogenic pesticide-associated N-nitroso (PANN) compounds....
Analysis of human serum and urine for tentative identification of potentially carcinogenic pesticide-associated N-nitroso compounds using high-resolution mass spectrometry.
Human serum and urine samples were analyzed for a suite of nitrosatable pesticides and potentially carcinogenic pesticide-associated N-nitroso (PANN) compounds. Formation of PANN compounds may occur in vivo after consumption of food or water containing trace amounts of nitrosatable pesticide residues and nitrate. Using a modified version of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method, nine nitrosatable pesticides and byproducts were extracted from serum and urine from 64 individuals from two different sample populations in Atlantic Canada: (i) Prince Edward Island, a region where nitrate and trace amounts of nitrosatable pesticides have been detected in groundwater; and (ii) Halifax, Nova Scotia, a non-agricultural urban area. Samples were then analyzed using ultra-high pressure liquid chromatography (UHPLC) coupled with high-resolution accurate mass (HRAM) single-stage orbitrap mass spectrometry (MS), which allows for semi-targeted analysis and tentative identification of a virtually limitless number of exposure biomarkers. Two nitrosatable target analytes, ethylenethiourea (ETU) and 3,5,6-trichloro-2-pyridinol (TCPy) were found in serum, while atrazine (ATR) and ETU were detected in urine. Five and six PANN compounds were tentatively identified in serum and urine, respectively. The two PANN compounds that were most frequently tentatively identified in serum were N-nitroso dimethoate (N-DIM) and N-nitroso omethoate (N-OME) with detection frequencies of 78% and 95%, respectively. This is the first biomonitoring study of its kind to investigate PANN compounds in human serum and urine.
Topics: Carcinogens; Chromatography, High Pressure Liquid; Humans; Mass Spectrometry; Nitroso Compounds; Pesticide Residues; Pesticides
PubMed: 34896088
DOI: 10.1016/j.envres.2021.112493 -
PeerJ 2021High doses of ethylenebisdithiocarbamate (EBDC) are used in banana production, and unused pesticide mixture (solution) is often disposed of improperly. This can result...
BACKGROUND
High doses of ethylenebisdithiocarbamate (EBDC) are used in banana production, and unused pesticide mixture (solution) is often disposed of improperly. This can result in soil and water contamination and present an undue risk to rural communities and the environment. An alternative to reduce the environmental impacts caused by pesticide residues is the biobeds treatment. It is necessary to establish if the composition of the proposed biomixtures supports microbial activity to degrade pesticides in biobeds. This research aimed to evaluate the EBDC effect on the distribution and abundance of microbial populations in polluted biomixtures .
METHODS
For this purpose, a biomixture based on banana stem, mulch, and Fluvisol soil (50:25:25% v/v) was prepared and polluted with 1,000 mg L EBDC. The response variables kinetics were determined every 14 days for three months, such as pH, organic matter, moisture, cation exchange capacity, microbial colonies, and cell counts at three depths within the experimental units.
RESULTS
EBDC reduced the number of microbial colonies by 72%. Bacterial cells rapidly decreased by 69% and fungi 89% on the surface, while the decrease was gradual and steady at the middle and bottom of the biobed. The microbial populations stabilized at day 42, and the bacteria showed a total recovery on day 84, but the fungi slightly less. At the end of the experiment, the concentration of EBDC in the biomixture was 1.3-4.1 mg L. A correlation was found between fungal count (colonies and cells) with EBDC concentration. A replacement of the biomixture is suggested if the bacterial population becomes less than 40 × 10 CFU mL and the fungal population less than 8 × 10 CFU mL or if the direct cell count becomes lower than 50 × 10 cells mL in bacteria and 8 × 10 cells mL in fungi.
CONCLUSION
The biomixture based on banana stem supports the microbial activity necessary for the degradation of the EBDC pesticide. It was found that fungi could be used as indicators of the pollutant degradation process in the biomixtures. Microbial counts were useful to establish the mobility and degradation time of the pesticide and the effectiveness of the biomixture. Based on the results, it is appropriate to include the quantification of microbial populations to assess the effectiveness of pesticide degradation and the maturity level of the biomixture.
PubMed: 34616634
DOI: 10.7717/peerj.12200 -
Acta Histochemica Jan 2020Anorectal malformations (ARMs) are common congenital malformations of the terminal digestive tract, but little is known regarding their pathogenesis. Aberrant cell...
BACKGROUND
Anorectal malformations (ARMs) are common congenital malformations of the terminal digestive tract, but little is known regarding their pathogenesis. Aberrant cell proliferation/apoptosis are believed to be involved in ARMs. However, there are no studies on proliferation/apoptosis-related genes.
PURPOSE
We aimed to investigate the spatiotemporal expression patterns of two proliferation/apoptosis-related genes (MYC proto-oncogene and tumor protein p53) and explore their potential functions in the hindguts of ethylene thiourea-induced ARMs rat fetuses.
METHODS
MYC and p53 expression was evaluated using immunohistochemical staining, western blotting, and quantitative real-time polymerase chain reaction (RT-qPCR). Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and p53 costaining were performed to assay the colocalization of apoptotic and p53-expressing cells.
RESULTS
Rat fetuses with ARMs displayed fusion failure of the urogenital septum and cloacal membrane. In the control group, MYC was persistently expressed from gestational day (GD)14 to GD16 and distributed throughout the hindgut, while p53 was weakly detected in the terminal segment of the urethra and hindgut; in the ARMs group, MYC expression was obviously reduced, while p53 was widely and highly expressed in the urethra and hindgut. Western blotting and RT-qPCR confirmed the decrease in MYC and increase in p53 expression in ARMs. TUNEL and p53 co-staining revealed considerable overlap between apoptotic and p53-expressing cells.
CONCLUSION
The expression patterns of c-myc and p53 were disrupted in ARMs rat embryos, and the downregulation of c-myc and upregulation of p53 might be related to the development of ARMs at the key time points of ARMs morphogenesis.
Topics: Animals; Anorectal Malformations; Apoptosis; Cell Proliferation; Ethylenethiourea; Female; Fetus; Gene Expression Regulation, Developmental; Intestines; Pregnancy; Proto-Oncogene Proteins c-myc; Rats; Rats, Wistar; Tumor Suppressor Protein p53
PubMed: 31787253
DOI: 10.1016/j.acthis.2019.151466 -
International Journal of Environmental... Aug 2022Mancozeb (MNZ) is a fungicide commonly employed in many countries worldwide. This study assesses MNZ absorption dynamics in 19 greenhouse farmers, specifically following...
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 pesticides daily, as well as to clarify the occupational exposure levels to ETU.
Topics: Advanced Oxidation Protein Products; Biomarkers; Ethylenethiourea; Farmers; Humans; Maneb; Occupational Exposure; Oxidative Stress; Pesticides; Zineb
PubMed: 36078202
DOI: 10.3390/ijerph191710486 -
Environmental Pollution (Barking, Essex... Jan 2022Toxicological and epidemiological studies implicate exposure to dithiocarbamate (DTC) fungicides in adverse health outcomes. However, there is limited information about...
Toxicological and epidemiological studies implicate exposure to dithiocarbamate (DTC) fungicides in adverse health outcomes. However, there is limited information about human exposure to these chemicals. This systematic review determined to which extent human populations worldwide, including children, pregnant women, and adults, are exposed environmentally or occupationally to DTC pesticides and how these exposures compare to the NHANES 2003-2008 population, using urinary ETU data as an outcome measure. PubMed, Embase, and SciFinder were searched using the keywords "ethylenethiourea" or CAS No.: 96-45-7, and urine or urinary. Duplicates and irrelevant studies were removed from the search results based on predetermined exclusion criteria. This screening process identified 17 relevant papers. One additional paper was found independent of this search. Data from studies were extracted using a pre-established data collection form. Ten, two, and five manuscripts reported urinary levels in environmentally exposed adults, children, and pregnant women, respectively. Median ETU levels ranged from 0.15 to 4.7 μg/g creatinine in adults (1994-2017), 0.24-0.83 μg/g creatinine in children (2011), and 2.6-5.24 ng/ml in pregnant women (2011). Eight studies reported urinary ETU levels in mostly agriculturally exposed populations, with median ETU levels ranging from 0.42 to 49.6 μg/g creatinine (1999-2011). With one exception, all studies were conducted between 1994 and 2011. ETU levels in the NHANES 2003-2008 population appeared to be generally lower than most studies identified in this review. This finding suggests that, historically, DTC fungicide exposures in the general population of high-income countries, such as the US, were low, whereas agricultural populations may have experienced higher exposure. Unfortunately, more recent exposure data are missing, especially in countries where DTC pesticides are not being phased out.
Topics: Adult; Biological Monitoring; Biomarkers; Child; Ethylenethiourea; Female; Fungicides, Industrial; Humans; Nutrition Surveys; Pregnancy
PubMed: 34751155
DOI: 10.1016/j.envpol.2021.118419 -
Molecular Diversity Jun 2023Imidazolidine-2-thione substructure represents a pharmaceutically attractive scaffold, being included in different antimicrobial, anticancer and pesticide agents. To...
Imidazolidine-2-thione substructure represents a pharmaceutically attractive scaffold, being included in different antimicrobial, anticancer and pesticide agents. To further evaluate the pharmaceutical potential of this chemical moiety, imidazolidine-2-thione was reacted with atypical Vilsmeier adducts, obtained by the condensation between dimethylacetamide and various acyl chlorides endowed with different electronic and steric properties. The formation of mono-acylated or di-acylated thiourea derivatives emerged to be affected by the nature of the considered acyl chloride reagent. Computational semi-empirical simulations were carried out to rationalize the relevant factor influencing the outcome of the reaction. As acylthioureas are pharmacologically relevant compounds, the chemical versatility of mono-acylated derivatives were evaluated by reacting benzoyl imidazolidin-2-thione with acyl chlorides. A small library of asymmetric di-acylthioureas was prepared and the obtained derivatives did not show any cytotoxicity on SKOV-3 and MCF-7 cancer cell lines. Additionally, in silico studies predicted good pharmacokinetics properties and promising drug-like characteristics for mono- and di-acylated thioureas. These considerations further support the value of the prepared compounds as interesting non-cytotoxic chemical scaffold useful in the medicinal chemistry field.
Topics: Humans; Ethylenethiourea; Chlorides; Thiourea; MCF-7 Cells
PubMed: 35867289
DOI: 10.1007/s11030-022-10487-5 -
Frontiers in Genetics 2021Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous...
Anorectal malformations (ARMs) are among the most common congenital terminal digestive tract malformations. Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, play roles in the development of the digestive system; however, their contributions to the pathogenesis of ARMs are not well-established. In this study, we explored the mechanism underlying ethylenethiourea (ETU)-induced ARMs by profiling circRNA expression via RNA-seq and constructing a regulatory circRNA-miRNA-mRNA network. Nine pregnant rats were gavage-fed a single dose of 125 mg/kg 1% ETU (ARM group) on gestational day 10 (GD10), and another 9 pregnant rats received a similar dose of saline (normal group) as a control. Embryos were obtained by cesarean section on the key time-points of anorectal development (GD14, GD15, and GD16). Hindgut samples isolated from the fetuses were evaluated by high-throughput sequencing and differentially expressed circRNAs were validated by reverse transcription-quantitative polymerase chain reaction, agarose gel electrophoresis, and Sanger cloning and sequencing. A total of 18295 circRNAs were identified in the normal and ARM groups. Based on the 425 differentially expressed circRNAs (|Fc| > 2, p < 0.05), circRNA-miRNA and miRNA-mRNA pairs were predicted using miREAP, miRanda, and TargetScan. A total of 55 circRNAs (14 up- and 41 downregulated in the ARM group compared to the normal group) were predicted to bind to 195 miRNAs and 947 mRNAs. Competing endogenous RNA networks and a Kyoto Encyclopedia of Genes and Genomes analysis revealed that novel_circ_001042 had the greatest connectivity and was closely related to ARM-associated signaling pathways, such as the Wingless Type MMTV integration site family, mitogen-activated protein kinase, and transforming growth factor-β pathways. These results provide original insight into the roles of circRNAs in ARMs and provide a valuable resource for further analyses of molecular mechanisms and signaling networks.
PubMed: 33927745
DOI: 10.3389/fgene.2021.605015