Search Results (7)

Background. In January 2021, the European Union ended the license of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, because of some properties typical of human carcinogens. This decision contrasts the IARC classification of EBDC fungicides (Group 3, not classifiable as to human carcinogenicity). A systematic review of the scientific literature was conducted to explore the current evidence. Methods. Human and experimental studies of cancer and exposure to EBDC fungicides (Mancozeb, Maneb, Zineb, and others) and ethylene thiourea (ETU), their major metabolite, published in English as of December 2021, were retrieved using PubMed, the list of references of the relevant reports, and grey literature. Results. The epidemiological evidence of EBDC carcinogenicity is inadequate, with two studies each suggesting an association with melanoma and brain cancer and inconsistent findings for thyroid cancer. Experimental animal studies point at thyroid cancer in rats and liver cancer in mice, while multiple organs were affected following the long-term oral administration of Mancozeb. The mechanism of thyroid carcinogenesis in rats has also been shown to occur in humans. Genotoxic effects have been reported. Conclusions. The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted. Full article

(1) Background: The impact of occupational exposure to high doses of pesticides on hematologic disorders is widely studied. Yet, lifelong exposure to low doses of pesticides, and more particularly their cocktail effect, although poorly known, could also participate to the development of such hematological diseases as myelodysplastic syndrome (MDS) in elderly patients. (2) Methods: In this study, a cocktail of seven pesticides frequently present in water and food (maneb, mancozeb, iprodione, imazalil, chlorpyrifos ethyl, diazinon and dimethoate), as determined by the European Food Safety Authority, were selected. Their in vitro effects at low-doses on primary BM-MSCs from healthy volunteers were examined. (3) Results: Exposure of normal BM-MSCs to pesticides for 21 days inhibited cell proliferation and promoted DNA damage and senescence. Concomitantly, these cells presented a decrease in aldehyde dehydrogenase 2 (ALDH2: mRNA, protein and enzymatic activity) and an increase in acetaldehyde levels. Pharmacological inhibition of ALDH2 with disulfiram recapitulated the alterations induced by exposure to low doses of pesticides. Moreover, BM-MSCs capacity to support primitive hematopoiesis was significantly altered. Similar biological abnormalities were found in primary BM-MSCs derived from MDS patients. (4) Conclusions: these results suggest that ALDH2 could participate in the pathophysiology of MDS in elderly people long exposed to low doses of pesticides. Full article

A major problem in psychiatric research is a deficit of relevant cell material of neuronal origin, especially in large quantities from living individuals. One of the promising options is cells from the olfactory neuroepithelium, which contains neuronal progenitors that ensure the regeneration of olfactory receptors. These cells are easy to obtain with nasal biopsies and it is possible to grow and cultivate them in vitro. In this work, we used RNAseq expression profiling and immunofluorescence microscopy to characterise neurospheres-derived cells (NDC), that simply and reliably grow from neurospheres (NS) obtained from nasal biopsies. We utilized differential expression analysis to explore the molecular changes that occur during transition from NS to NDC. We found that processes associated with neuronal and vascular cells are downregulated in NDC. A comparison with public transcriptomes revealed a depletion of neuronal and glial components in NDC. We also discovered that NDC have several metabolic features specific to neuronal progenitors treated with the fungicide maneb. Thus, while NDC retain some neuronal/glial identity, additional protocol alterations are needed to use NDC for mass sample collection in psychiatric research. Full article

Cercospora leaf spot of olive (CLSO), caused by Pseudocercospora cladosporioides, is one of the most important foliar diseases of olives worldwide. This study aimed to evaluate the effect of a wide range of fungicides on mycelial growth and conidial germination of P. cladosporioides in vitro, and to evaluate the effect of several fungicides, application timings and management strategies (conservative and risky) to control CLSO under field conditions. Of the studied fungicides, strobilurin compounds and benomyl were the most effective active ingredients, followed by folpet, captan and maneb, in inhibiting mycelial growth and conidial germination. The pyraclostrobin + boscalid treatment was effective under field conditions, even without the application of supplementary copper. Treatments conducted in October or March were more effective than those conducted in May. Management strategies based on the author’s experience reduced copper applications up to 32.0% and 50.0% (conservative and risky strategy, respectively) in comparison to the reduction with the traditional strategy, without increasing CLSO incidence. This work provides useful information about effective formulations against CLSO and a reduction in unnecessary fungicide applications in an effort to implement IPM in olive orchards under Mediterranean conditions. Full article

Pesticides belong to a group of xenobiotics harmful to humans and wildlife, whose fate and activity depends on their susceptibility to degradation. Therefore, the monitoring of their residue level in agricultural soils is very important because it provides very valuable information on the actual level of soil contamination and environmental risk resulting from their application. The aim of this study was to evaluate contemporary concentrations of organochlorine (OCPs) and non-chlorinated pesticides (NCPs) in arable soils of Poland as an example of Central and Eastern European countries. The results were assessed in relation to Polish regulations, which are more restrictive compared to those of other European countries. The sampling area covered the territory of arable lands in Poland (216 sampling points). The distribution of sampling points aimed to reflect different geographical districts, conditions of agricultural production, and various soil properties. The collected soil samples were extracted with organic solvents in an accelerated solvent extractor (ASE 2000). The OCPs, including α-HCH, β-HCH, γ-HCH, and p,p’DDT, p,p’DDE, and p,p’DDD, were extracted with a hexane/acetone mixture (70:30 v/v) and determined by gas chromatography with an electron capture detector (GC-μECD). NCPs included atrazine, carbaryl, and carbofuran were extracted with a dichloromethane/acetone mixture (50:50 v/v), while maneb was extracted by intensive shaking the sample with acetone (1:1 v/v) and ethylenediamine-tertraacetic acid. The NCPs were identified by a dual mass- spectrometry (GC-MS/MS). The total content of individual OCPs ranged from 0.61 to 1031.64 µg kg⁻¹, while the NCP concentrations were significantly lower, from 0.01 to 43.92 µg kg⁻¹. DDTs were detected in all soils samples (p,p’DDD (23.60 µg kg⁻¹) > p,p’DDT (18.23 µg kg⁻¹) > p,p’DDE (4.06 µg kg⁻¹), while HCHs were only in 4% of the analyzed samples (β-HCH (339.55 µg kg⁻¹) > α-HCH (96.96 µg kg⁻¹) > γ-HCH (3.04 µg kg⁻¹)), but in higher values than DDTs. Among NCPs, higher concentration was observed for carbaryl (<0.01–28.07 µg kg⁻¹) and atrazine (<0.01–15.85 µg kg⁻¹), while the lower for carbofuran (<0.01–0.54 µg kg⁻¹). Maneb was not detected in analyzed soils. Assessment of the level of soil pollution based on Polish regulations indicated that several percentages of the samples exceeded the criterion for OCPs, such as ∑3DDTs (14 samples; 6.5% of soils) and HCH congeners (α-HCH in one sample; 0.5% of soils), while NCP concentration, such as for atrazine, carbaryl and carbofuran were below the permissible levels or were not detected in the analyzed soils, e.g., maneb. The obtained results indicated that residues of the analyzed pesticides originate from historical agricultural deposition and potentially do not pose a direct threat to human and animal health. The behavior and persistence of pesticides in the soils depend on their properties. Significantly lower NCP concentration in the soils resulted from their lower hydrophobicity and higher susceptibility to leaching into the soil profile. OCPs are characterized by a high half-life time, which affect their significantly higher persistence in soils resulting from affinity to the soil organic phase. Full article

We previously found that carbamate pesticides induced significant apoptosis in human natural killer cells. To investigate whether carbamate pesticides also induce apoptosis in human T lymphocytes, in the present study Jurkat human T cells were treated in vitro with thiram, maneb, carbaryl or ziram. Apoptosis was determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspase 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that thiram, ziram, maneb and carbaryl also induced apoptosis in a time- and dose-dependent manner in the human T cells. However, the strength of the apoptosis-inducing effect differed among the pesticides, with the: thiram > ziram > maneb > carbaryl. Moreover, thiram significantly increased the intracellular level of active caspase 3 and caspase inhibitors significantly inhibited apoptosis. Thiram also significantly caused mitochondrial cytochrome-c release. These findings indicate that carbamate pesticides can induce apoptosis in human T cells, and the apoptosis is mediated by the activation of caspases and the release of mitochondrial cytochrome-c. Full article

Parkinson’s disease (PD) is a common neurodegenerative movement disorder that is characterized pathologically by a progressive loss of midbrain dopaminergic neurons and by protein inclusions, designated Lewy bodies and Lewy neurites. PD is one of the most common neurodegenerative diseases, affecting almost 1% of the population over 60 years old. Although the symptoms and neuropathology of PD have been well characterized, the underlying mechanisms and causes of the disease are still not clear. Genetic mutations can provide important clues to disease mechanism, but most PD cases are sporadic rather than familial; environmental factors have long been suspected to contribute to the disease. Although more than 90% of PD cases occur sporadically and are thought to be due, in part, to oxidative stress and mitochondrial dysfunction, the study of genetic mutations has provided great insight into the molecular mechanisms of PD. Furthermore, rotenone, a widely used pesticide, and paraquat and maneb cause a syndrome in rats and mice that mimics, both behaviorally and neurologically, the symptoms of PD. In the current review, we will discuss various aspects of gene-environment interaction that lead to progressive dopaminergic neurodegenration, mainly focusing on our current finding based on stress-mediated parkin dysfunction. Full article