scholarly journals Risk Assessment of the Metabolite M44 of Bixafen, One of the Active Substancesin Aviator Xpro EC225

2019 ◽  
pp. 317-318
Author(s):  
Jan Ludvig Lyche ◽  
Hubert Dirven ◽  
Marit Låg ◽  
Asbjørn Magne Nilsen ◽  
Katrine Borgå ◽  
...  
Keyword(s):  
Food Safety ◽  
Plant Protection ◽  
Experimental Studies ◽  
Plant Protection Products ◽  
Guidance Document ◽  
Developmental Effects ◽  
Historical Control Data ◽  
The Eu

Aviator Xpro EC 225 containing the active substance bixafen was assessed by VKM in spring 2013, and it was concluded that the metabolite M44 has potential for groundwater contamination. Furthermore, VKM assessed in late 2013 the relevance of this metabolite in accordance with the EU guidance document on metabolites in groundwater, and concluded that the malformations observed in rabbits exposed to the metabolite should be considered treatment related. VKM also concluded that the data presented to evaluate the possible genotoxic properties of the metabolite was insufficient to reach a conclusion. Based on this, the Norwegian Food Safety Authority rejected the approval of Aviator Xpro EC 225. The applicant has now submitted results from an in vivo study to strengthen the basis for assessment of genotoxic properties, and also submitted new historical controls in relation to the experimental studies on foetal developmental effects in rabbits. The VKM Panel on Plant Protection Products has discussed the questions raised by The Norwegian Food Safety Authority on the basis of the new data, and has the following opinion: On the assessment of genotoxic properties of the M44 metabolite of bixafen, one of the active ingredients of Aviator Xpro EC 225. It is the view of VKM Panel on Plant Protection Products that the new in vivo mouse micronucleus study, supplemented together with a separate study demonstrating bioavailability, overrides the results of the in vitro clastogenicity studies. Taken together, it is the opinion of VKM that under the conditions studied, M44 should be considered as non-genotoxic. On the assessment of the relevance of the foetal malformations in M44 exposed animals. VKMs Panel on Plant Protection products has assessed the arguments and new historical control data presented by the applicant, intended to show that metabolite M44 is not teratogenic. It is however the opinion of the Panel that the arguments and the new historical data provided by the applicant do not alter the panel’s previous conclusion; that the malformations observed in rabbits exposed to the metabolite M44 should be considered treatment related.

scholarly journals Risk Assessment of the Active Plant Protection Product Ingredient MCPA (4-chloro-2-methylphenoxyacetic acid): AOEL and ADI Determination

2019 ◽  
pp. 38-39
Author(s):  
Asbjørn Magne Nilsen ◽  
Hubert Dirven ◽  
Jan Ludvig Lyche ◽  
Marit Låg ◽  
Katrine Borgå ◽  
...  
Keyword(s):  
Food Safety ◽  
Plant Protection ◽  
Absorbed Dose ◽  
Plant Protection Products ◽  
Dermal Absorption ◽  
Renal Effects ◽  
In Vivo Experiments

MCPA (4-chloro-2-methylphenoxyacetic acid) is the active ingredient in several registered herbicides. VKM concluded in 2006 that the effects observed in experiments with dogs were of little relevance to humans, and an AOEL value of 0.036 mg/kg bw/day was proposed, based on renal effects in a 90-day study in rats. The manufacturer is of the opinion that AOEL should be set to 0.11 mg/kg bw/day, and ADI to 0.05 mg/kg bw/day, based on the view that since a 90-day and 2-year study in rats were conducted in the same lab using the same rat strain, it is reasonable to eliminate effects which are not reproduced in both sets of data. The Norwegian Food Safety Authority has therefore requested VKM’s Panel for Plant Protection Products for an opinion on the determination of NOAEL values based on the 90-day and 2-year studies in rats, and consider if it is acceptable to use the manufacturer's approach for an overall consideration of the submitted studies. The Panel has discussed the findings in the two rat studies and concluded that it is not considered acceptable that individual studies separated by several years, in this case studies performed in 1985 and 1988, are taken together and data not reproduced in both sets eliminated. The Panel is still of the opinion that both AOEL and ADI for MCPA should be set to 0.036 mg/kg bw/day based on a NOAEL of 3.6 mg/kg bw/day (50 ppm) from assessment of the renal effects in the 90-day study in rats. The manufacturer has also requested a reconsideration of the present values for dermal absorption which was set by the Norwegian Food Safety Authority during the administrative review of the product MCPA 750 Liquid in 2013. VKM’s Panel on Plant Protection Products supports the conclusion of the Norwegian Food Safety Authority concerning the determination of values for dermal absorption of MCPA. This includes the consideration of remaining substance in skin after washing as part of the absorbed dose in the in vitro studies, and the use of the same experimental time period in the in vitro and in vivo experiments as a basis for the so-called “Triple-pack-approach” for determination of human dermal absorption.

scholarly journals Application of the Threshold of Toxicological Concern (TTC) in Food Safety: Challenges and Opportunities

2021 ◽  
Vol 3 ◽  
Author(s):  
Rositsa Serafimova ◽  
Tamara Coja ◽  
George E. N. Kass
Keyword(s):  
Food Safety ◽  
Plant Protection ◽  
Plant Protection Products ◽  
The European Union ◽  
Use Of Data ◽  
Challenges And Opportunities ◽  
Guidance Documents ◽  
Threshold Of Toxicological Concern ◽  
Active Substances

The safety assessment of chemicals added or found in food has traditionally made use of data from in vivo studies performed on experimental animals. The nature and amount of data required to carry out a risk assessment is generally stipulated either in the different food legislations or in sectoral guidance documents. However, there are still cases where no or only limited experimental data are available or not specified by law, for example for contaminants or for some minor metabolites from active substances in plant protection products. For such cases, the Threshold of Toxicological Concern (TTC) can be applied. This review explores the use of the TTC approach in food safety in the European Union, in relation to the different food sectors, legal requirements and future opportunities.

scholarly journals The role of the European Food Safety Authority in the active substance approval and renewal procedures within the EU pesticide policy

2021 ◽  
Vol 60 (90) ◽  
pp. 165-187
Author(s):  
Slađana Mladenović
Keyword(s):  
Food Safety ◽  
Active Substance ◽  
Plant Protection ◽  
Plant Protection Products ◽  
Scientific Output ◽  
European Food Safety Authority ◽  
Scientific Quality ◽  
Analysis Model ◽  
Member States ◽  
The Eu

The EU decentralised agencies are involved in various sectorial EU policies and related composite procedures. One of the agencies, the European Food Safety Authority (EFSA), has a prominent role in the composite procedures within the EU pesticide policy - the active substance approval and renewal procedures. These procedures represent the initial steps in the complex administrative process of placing on the market and control of use of plant protection products. The procedures are arranged under the linear risk analysis model within which the scientific risk assessment is performed by Member States and the EFSA, while the political risk management is performed by the Commission and Member States in the comitology procedure. After a brief analysis of the key stages and outcomes of the procedures, the paper discusses two topics. The first relates to the properties of three key aspects of the EFSA's role in the procedures: 1) involvement in adopting guidance documents; 2) publishing appropriate documents and deciding on confidentiality requests; and 3) preparing and submitting the conclusion, its main scientific output related to active substance. The second topic includes five elements of confidence in the EFSA regarding the course and outcome of the procedure: efficiency, independence, transparency, high scientific quality and effective risk communication. The paper discusses the properties of the elements, the main identified challenges associated with them, as well as ongoing and future responses to these challenges, especially those introduced by the Transparency Regulation, adopted in 2019 and applicable from 27 March 2021.

scholarly journals Specifics of pesticides effects on the phytopathogenic bacteria

2016 ◽  
Vol 23 (2) ◽  
pp. 311-331 ◽  
Author(s):  
Volodymyr Patyka ◽  
Natalia Buletsa ◽  
Lidiya Pasichnyk ◽  
Natalia Zhitkevich ◽  
Antonina Kalinichenko ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Plant Protection ◽  
Plant Protection Products ◽  
Ease Of Use ◽  
Chemical Pollution ◽  
Resistance Response ◽  
Phytopathogenic Bacteria ◽  
Long Term Storage

Abstract The data concerning the effects of pesticides of different nature on the phytopathogenic bacteria was examined and summarized. Without extensive research on the mechanisms of interaction between pathogenic bacteria and pesticides in the literature review a similar message about microorganisms of soil and phyllosphere are included. The bacteria can be suppressed permanently by pesticides with a mechanism of action that universally affects biological processes in living systems. Long-term storage, ease of use and fast visible effect are the advantages of synthetic pesticides remedies. But chemical pollution, shifts in the balance of ecosystems, unpredictable effects of chemical pesticides on non-target objects are the drawbacks. Stimulation of resistance response in plants is unifying factor for all types of biopesticides. This is realized through localization of the pathogen during infection, blocking its further penetration, distribution and reproduction. The results of the study of effects of plant protection products on the phytopathogenic bacteria of main crops are described. Among all tested pesticides, thiocarbamate fungicides demonstrated significant inhibitory action on phytopathogens, but their effect may be neutralized by other constituents of multicomponent preparations. Triazole fungicides affect the causative agents of bacterioses of crops at a dose of more than 1% of the active substance in the nutrient medium. Insecticides and herbicides have little or no effect on phytopathogenic bacteria; however they can enhance morphological dissociations of some Pseudomonas strains, thereby increasing their ability to survive. The disadvantage of many biopesticides against phytopathogenic microorganisms is the difference between their efficacy in vitro and in vivo that is why the desired result is not achieved in field condition. In addition, biological pesticides often lose their activity causing the problem of constant search for new active antagonists. The fact that the sensitivity of phytopathogenic bacteria to pesticides is strain-dependent should be considered in practice, particularly, assessment of the antibacterial action of various preparations should not be limited to a single bacterial strain.

scholarly journals Ammonium glufosinate and triazine herbicides have side effects on soil microorganisms and pathogens

2019 ◽  
pp. 6-11
Author(s):  
I. Storchous ◽  
Yu. Stefkivska
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Soil Microorganisms ◽  
Plant Protection ◽  
Plant Protection Products ◽  
Symbiotic Relationships ◽  
Ammonium Glufosinate ◽  
Negative Side Effects

Goal. Analysis and synthesis of research results regarding the beneficial and negative side effects of ammonium glufosinate and thiazine herbicides on microorganisms. Methods. System-analytical, abstract-logical, empirical. Results. Information on the side effects of herbicides with the content of the active substance glufosinate ammonium and derivatives of thiazine herbicides is given. One of the side effects of herbicides that attracts attention is their biological activity. The biological activity of herbicides goes beyond the effects on target organisms and, thus, herbicides can influence the plant-pathogen interaction through their effect on the causative agent or on the surrounding soil microorganisms, including symbiotic relationships. As a side effect, both a decrease and an increase in diseases caused by phytopathogens that affect leaves, stems or roots are established. However, in some cases, the results obtained in in vitro experiments differed from the results obtained in field conditions in vivo or on a host plant. The phenomenon of the manifestation of side effects of herbicides was first discovered in the early 1940s and began to be studied in more detail since 1960. Conclusions. Generalized information about the history, studies of the side effects of herbicides on different cultures and in different conditions in the world. It is important that such effects are not fully studied, and these mechanisms attract the attention of scientists for their further research. Future studies are planned to be carried out using high-precision methods, such as chip-based technologies, to study all the mechanisms involved in the pathogen-plant interaction, which are modulated by herbicides. This trilateral relationship today is studied as a molecular and biochemical cross-linkage between a plant and a pathogen, a plant and a herbicide, as well as a pathogen and a herbicide. Active studies by foreign scientists of the side effects of herbicides show that in Ukraine, as an agrarian state, it is necessary to purposefully investigate the effect of herbicides on soil microorganisms and pathogens to optimize the use of plant protection products in agricultural production.

scholarly journals A Review on the Medicinal and Pharmacological Properties of Traditional Ethnomedicinal Plant Sonapatha, Oroxylum indicum

Sinusitis ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 71-89
Author(s):  
Ganesh Chandra Jagetia
Keyword(s):  
Glucose Transporter ◽  
Skin Diseases ◽  
Regulatory Element ◽  
Experimental Studies ◽  
Fatty Acid Synthetase ◽  
Preclinical Models ◽  
Oroxylin A ◽  
Oroxylum Indicum

Oroxylum indicum, Sonapatha is traditionally used to treat asthma, biliousness, bronchitis, diarrhea, dysentery, fevers, vomiting, inflammation, leukoderma, skin diseases, rheumatoid arthritis, wound injury, and deworm intestine. This review has been written by collecting the relevant information from published material on various ethnomedicinal and pharmacological aspects of Sonapatha by making an internet, PubMed, SciFinder, Science direct, and Google Scholar search. Various experimental studies have shown that Sonapatha scavenges different free radicals and possesses alkaloids, flavonoids, cardio glycosides, tannins, sterols, phenols, saponins, and other phytochemicals. Numerous active principles including oroxylin A, chrysin, scutellarin, baicalein, and many more have been isolated from the different parts of Sonapatha. Sonapatha acts against microbial infection, cancer, hepatic, gastrointestinal, cardiac, and diabetic disorders. It is useful in the treatment of obesity and wound healing in in vitro and in vivo preclinical models. Sonapatha elevates glutathione, glutathione-s-transferase, glutathione peroxidase, catalase, and superoxide dismutase levels and reduces aspartate transaminase alanine aminotransaminase, alkaline phosphatase, lactate dehydrogenase, and lipid peroxidation levels in various tissues. Sonapatha activates the expression of p53, pRb, Fas, FasL, IL-12, and caspases and inhibited nuclear factor kappa (NF-κB), cyclooxygenase (COX-2), tumor necrosis factor (TNFα), interleukin (IL6), P38 activated mitogen-activated protein kinases (MAPK), fatty acid synthetase (FAS), sterol regulatory element-binding proteins 1c (SREBP-1c), proliferator-activated receptor γ2 (PPARγ2), glucose transporter (GLUT4), leptin, and HPV18 oncoproteins E6 and E7 at the molecular level, which may be responsible for its medicinal properties. The phytoconstituents of Sonapatha including oroxylin A, chrysin, and baicalein inhibit the replication of SARS-CoV-2 (COVID-19) in in vitro and in vivo experimental models, indicating its potential to contain COVID-19 infection in humans. The experimental studies in various preclinical models validate the use of Sonapatha in ethnomedicine and Ayurveda.

scholarly journals Topical Application of Double-Stranded RNA Targeting 2b and CP Genes of Cucumber mosaic virus Protects Plants against Local and Systemic Viral Infection

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 963
Author(s):  
Maria C. Holeva ◽  
Athanasios Sklavounos ◽  
Rajendran Rajeswaran ◽  
Mikhail M. Pooggin ◽  
Andreas E. Voloudakis
Keyword(s):  
Cucumber Mosaic Virus ◽  
Mosaic Virus ◽  
Topical Application ◽  
Plant Virus ◽  
Plant Protection ◽  
Post Inoculation ◽  
Tobacco Plants ◽  
Double Stranded Rna

Cucumber mosaic virus (CMV) is a destructive plant virus with worldwide distribution and the broadest host range of any known plant virus, as well as a model plant virus for understanding plant–virus interactions. Since the discovery of RNA interference (RNAi) as a major antiviral defense, RNAi-based technologies have been developed for plant protection against viral diseases. In plants and animals, a key trigger of RNAi is double-stranded RNA (dsRNA) processed by Dicer and Dicer-like (DCL) family proteins in small interfering RNAs (siRNAs). In the present study, dsRNAs for coat protein (CP) and 2b genes of CMV were produced in vitro and in vivo and applied onto tobacco plants representing a systemic solanaceous host as well as on a local host plant Chenopodium quinoa. Both dsRNA treatments protected plants from local and systemic infection with CMV, but not against infection with unrelated viruses, confirming sequence specificity of antiviral RNAi. Antiviral RNAi was effective when dsRNAs were applied simultaneously with or four days prior to CMV inoculation, but not four days post inoculation. In vivo-produced dsRNAs were more effective than the in vitro-produced; in treatments with in vivo dsRNAs, dsRNA-CP was more effective than dsRNA-2b, while the effects were opposite with in vitro dsRNAs. Illumina sequencing of small RNAs from in vivo dsRNA-CP treated and non-treated tobacco plants revealed that interference with CMV infection in systemic leaves coincides with strongly reduced accumulation of virus-derived 21- and 22-nucleotide (nt) siRNAs, likely generated by tobacco DCL4 and DCL2, respectively. While the 21-nt class of viral siRNAs was predominant in non-treated plants, 21-nt and 22-nt classes accumulated at almost equal (but low) levels in dsRNA treated plants, suggesting that dsRNA treatment may boost DCL2 activity. Taken together, our findings confirm the efficacy of topical application of dsRNA for plant protection against viruses and shed more light on the mechanism of antiviral RNAi.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

scholarly journals Histone/protein deacetylases and T-cell immune responses

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2443-2451 ◽  
Author(s):  
Tatiana Akimova ◽  
Ulf H. Beier ◽  
Yujie Liu ◽  
Liqing Wang ◽  
Wayne W. Hancock
Keyword(s):  
T Cell ◽  
Cell Biology ◽  
T Regulatory Cells ◽  
Hdac Inhibitors ◽  
Experimental Studies ◽  
Cell Subset ◽  
Histone Protein ◽  
Anti Inflammatory

Abstract Clinical and experimental studies show that inhibition of histone/protein deacetylases (HDAC) can have important anti-neoplastic effects through cytotoxic and proapoptotic mechanisms. There are also increasing data from nononcologic settings that HDAC inhibitors (HDACi) can exhibit useful anti-inflammatory effects in vitro and in vivo, unrelated to cytotoxicity or apoptosis. These effects can be cell-, tissue-, or context-dependent and can involve modulation of specific inflammatory signaling pathways as well as epigenetic mechanisms. We review recent advances in the understanding of how HDACi alter immune and inflammatory processes, with a particular focus on the effects of HDACi on T-cell biology, including the activation and functions of conventional T cells and the unique T-cell subset, composed of Foxp3+ T-regulatory cells. Although studies are still needed to tease out details of the various biologic roles of individual HDAC isoforms and their corresponding selective inhibitors, the anti-inflammatory effects of HDACi are already promising and may lead to new therapeutic avenues in transplantation and autoimmune diseases.

scholarly journals Diabetic Cataract—Pathogenesis, Epidemiology and Treatment

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Andreas Pollreisz ◽  
Ursula Schmidt-Erfurth
Keyword(s):  
Experimental Studies ◽  
Disease Process ◽  
Basic Research ◽  
Polyol Pathway ◽  
Population Based ◽  
Diabetic Patients ◽  
Diabetic Cataract ◽  
Cataract Development

Cataract in diabetic patients is a major cause of blindness in developed and developing countries. The pathogenesis of diabetic cataract development is still not fully understood. Recent basic research studies have emphasized the role of the polyol pathway in the initiation of the disease process. Population-based studies have greatly increased our knowledge concerning the association between diabetes and cataract formation and have defined risk factors for the development of cataract. Diabetic patients also have a higher risk of complications after phacoemulsification cataract surgery compared to nondiabetics. Aldose-reductase inhibitors and antioxidants have been proven beneficial in the prevention or treatment of this sightthreatening condition in in vitro and in vivo experimental studies. This paper provides an overview of the pathogenesis of diabetic cataract, clinical studies investigating the association between diabetes and cataract development, and current treatment of cataract in diabetics.

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