scholarly journals Genotoxic Assessment of the Metabolite M-11 of Mepanipyrim, the Active Ingredient in the Plant Protection Product FRUPICA SC

2019 ◽  
pp. 306-307
Author(s):  
Hubert Dirven ◽  
Jan Ludvig Lyche ◽  
Marit Låg ◽  
Asbjørn Magne Nilsen ◽  
Katrine Borgå ◽  
...  
Keyword(s):  
Comet Assay ◽  
Rat Liver ◽  
Active Ingredient ◽  
Liver Tumors ◽  
Plant Protection ◽  
Plant Protection Products ◽  
In Vivo Studies ◽  
Plant Protection Product ◽  
Gamma Glutamyl Transpeptidase

The VKM Panel for plant protection products considered Frupica SC in a meeting on 25.11.2010, and found the active ingredient problematic with regard to carcinogenic effects and possible genotoxicity. M11 is a metabolite of mepanipyrim which is the active ingredient the plant protection product Frupica SC. The Norwegian Food Safety Authority has asked the applicant for further assessment of the genotoxic potential of the metabolite M11. The applicant has submitted a rat liver in vivo Comet assay of the metabolite, and the panel has been requested to consider if the genotoxic properties of mepanipyrim and the metabolite M11 is adequately documented.  The metabolite M11 caused positive findings in in vitro studies for bacterial mutation and chromosomal aberrations. Three in vivo studies (Micronucleus, unscheduled DNA synthesis and Comet assay) did not show evidence of genotoxicity. Based on the documentation available, VKMs Panel on Plant Protection Products concludes that mepanipyrim and the metabolite M11 should not be considered genotoxic in vivo. The lack of demonstrated in vivo genotoxicity makes it likely that mepanipyrim induces liver tumors in rats and mice by a mechanism that involves a threshold below which tumors are not expected to develop. This conclusion is strengthened by the finding of a promoter-like behavior of mepanipyrim for induction of gamma-glutamyl-transpeptidase positive foci in rat liver.

scholarly journals Ultrasonic Heating Detects Lipiodol Deposition within Liver Tumors after Transarterial Embolization: An In Vivo Approach

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 901
Author(s):  
Natsuhiko Saito ◽  
Toshihiro Tanaka ◽  
Kiyoyuki Minamiguchi ◽  
Ryosuke Taiji ◽  
Hideyuki Nishiofuku ◽  
...  
Keyword(s):  
Sound Velocity ◽  
Temperature Coefficient ◽  
Rat Liver ◽  
Liver Tumors ◽  
Transarterial Embolization ◽  
Rate Of Change ◽  
Accumulation Ratio ◽  
Ct Value ◽  
The Mean

Computed tomography (CT) is the standard method to evaluate Lipiodol deposition after transarterial embolization (TAE) for a long period. However, iodine but not Lipiodol can be observed on CT. A minimally invasive other method to detect Lipiodol has been needed to evaluate accurate evaluation after procedure. The purpose of this study was to evaluate the efficacy of using the rate of change in sound velocity caused by ultrasonic heating to reflect Lipiodol accumulation after TAE in a rat liver tumor model. We analyzed the association of this developed technique with CT images and histological findings. Eight rats bearing N1S1 cells were prepared. After confirmation of tumor development in a rat liver, Lipiodol was injected via the hepatic artery. Seven days after TAE, CT scan and sound velocity changes caused by ultrasonic heating were measured, and then the rats were sacrificed. An ultrasonic pulse-echo method was used to measure the sound velocity. The temperature coefficient of the sound velocity in each treated tumor was evaluated and compared with the mean CT value and the histological Lipiodol accumulation ratio. Pearson’s correlation coefficients were calculated to assess the correlation between the measured values. The correlation coefficient (r) of the mean CT value and histological Lipiodol accumulation ratio was 0.835 (p = 0.010), which was considered statistically significant. Also, those of the temperature coefficient of the sound velocity and the histological Lipiodol accumulation ratio were statistically significant (r = 0.804; p = 0.016). To our knowledge, this is the first study that reported the efficacy of ultrasonic heating to detect Lipiodol accumulation in rat liver tumors after TAE. Our results suggest that the rate of change in sound velocity caused by ultrasonic heating can be used to evaluate Lipiodol accumulation in liver tumors after TAE, and thus could represent an alternative to CT in this application. This new innovative technique is easy to treat and less invasive in terms of avoiding radiation compared with CT.

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.

The role of the enzyme-modified comet assay in in vivo studies

2020 ◽  
Vol 327 ◽  
pp. 58-68 ◽  
Author(s):  
Andrew Collins ◽  
Ariane Vettorazzi ◽  
Amaya Azqueta
Keyword(s):  
Comet Assay ◽  
In Vivo Studies

Compensatory Application Provisions of Plant Protection Products to Protect Biodiversity

2020 ◽  
pp. 1-17
Author(s):  
Alexander KOOF
Keyword(s):  
European Union ◽  
Indirect Effects ◽  
Plant Protection ◽  
Plant Protection Products ◽  
Plant Protection Product ◽  
Legal Basis ◽  
Federal Environmental Agency ◽  
German Federal Environmental Agency ◽  
German Federal Environmental ◽  
Environmental Agency

For the protection of biodiversity, the German Federal Environmental Agency (UBA) pursues the goal of establishing compensation areas to balance unavoidable indirect effects on nature and the environment caused by the application of plant protection products. Whether there is a legal basis for this within either European Union or national law is one of the most debated and pressing issues currently in the authorisation procedure for plant protection products in Germany. The purpose of this article is to provide a comprehensive legal assessment of whether it is legally permissible to make plant protection product authorisations contingent to compensatory application provisions to protect biodiversity.

scholarly journals A Herb-drug interaction study: Screen the inhibitory effects of Insulin plant extract on rat liver CYP2D6 isoenzyme upon concurrent administration of Aripiprazole

2020 ◽  
Vol 10 (3) ◽  
pp. 15-23
Author(s):  
Harshita Gupta ◽  
Bhagyashree Kamble
Keyword(s):  
Rat Liver ◽  
Plant Extract ◽  
Liver Microsomes ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Diabetic Patients ◽  
Concurrent Administration ◽  
High Blood Glucose ◽  
Successive Extraction

Aripiprazole belongs to the atypical antipsychotic category of drug. Cytochrome2D6 (CYP2D6) is one of the prominent enzymes that play a key role in the metabolism of Aripiprazole and further formation of an active metabolite, Dehydroaripiprazole takes place. Patients under the treatment with this potent moiety have been reported with the high blood glucose level as a side effect. In addition to this, literature suggests that the leaves of Insulin plant (Costus igneus) are usually administered by diabetic patients (2-3 times) to manage the sugar level without concerning to the physicians. There might be probability while concurrent administration of (Aripiprazole and Insulin plant leaves), leaves inhibit the enzyme and ultimately Dehydroaripiprazole exhibit poor pharmacological action. Hence, the present work was done to investigate the inhibitory effect of Insulin plant extract (IPE) on CYP2D6, with the co-administration of Aripiprazole (to examine the changes in a metabolite of Aripiprazole). In order to carry out this protocol firstly, IPE was prepared by the successive extraction method. Methanolic extract of Insulin plant was found enriched with the Quercetin, which was used as a marker to carry out this study. Presence of Quercetin was confirmed with the Ultra-violet spectroscopy (UV) and High-performance liquid chromatography (HPLC) analytical methods. Characterization of Aripiprazole was done with the help of different analytical tools such as: HPLC, melting point, and UV. Aripiprazole alone and with the several dilutions of IPE were incubated using isolated rat liver microsome (RLM) and analyzed using HPLC. HPLC data demonstrated that the, mixture of IPE+Aripiprazole (herb and drug in liver microsomes), in comparison to Aripiprazole+RLM (alone drug in liver microsomes) has not shown any significant inhibition of the enzyme, and inhibitory concentration (IC50) value found to be 4.49µg/ml. Therefore this study concluded that IPE has shown safe results even at the highest clinical dose after oral administration i.e., 20-1000µg/ml and did not show any significant CYP2D6 inhibition. Nevertheless, to confirm these observations, inclusion of in vivo studies will be advantageous. As per our knowledge, this is the first attempt made on the detection of Herb- Drug interactions (HDI’S) between Insulin plant and Aripiprazole.  

scholarly journals Effects of photopolymerisation on genotoxicity of composite adhesives in the comet assay

Genetika ◽  
2016 ◽  
Vol 48 (2) ◽  
pp. 617-627
Author(s):  
Stefan Dacic ◽  
Ninoslav Djelic ◽  
Milena Radakovic ◽  
Nada Lakic ◽  
Aleksandar Veselinovic ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Human Lymphocytes ◽  
Negative Control ◽  
In Vivo Studies ◽  
Halogen Lamp ◽  
Genotoxic Effects ◽  
Significant Difference ◽  
Isolated Human Lymphocytes

Certain in vivo studies have shown that the application of adhesives directly onto the open pulp or on a thin layer of dentin causes inflammation and pulpal abscesses. This reaction is related to toxic effects of monomers from adhesives. It has been confirmed that after proper illumination the adhesives become less toxic. The aim of the study was to examine genotoxicity of non-polymerised, partly polymerised and polymerised adhesives on isolated human lymphocytes using the alkaline Comet assay. Adper Single bond2 and Adper Easy One/3M ESPE adhesive photopolymerisation was performed by Elipar Highlight 3M ESPE halogen lamp for 0, 10 and 40 sec, at final concentrations of 100, 200, 500 and 1000 ?g/mL. With both adhesives, photopolymerisation at 0 and 10 seconds showed statistically significant increase in DNA damage in comparision to the negative control (solvent). On the other hand, after 40 seconds of photopolymerisation of both adhesives in all tested concentrations, the degree of DNA damage in Comet assay had no significant difference (P>0.05, ?2 test) compared to the negative control. Therefore, only the 40 seconds of photopolymerisation prevented genotoxic effects of both adhesives in the Comet assay.

scholarly journals COMPARATIVE INVESTIGATION OF GENOTOXIC ACTIVITY OF GLYPHOSATE TECHNICAL PRODUCTS IN THE MICRONUCLEUS TEST IN VIVO

2018 ◽  
pp. 24-28 ◽  
Author(s):  
N. A. Ilyushina ◽  
N. S. Averianova ◽  
G. V. Masaltsev ◽  
Yu. A. Revazova
Keyword(s):  
Plant Protection ◽  
Micronucleus Test ◽  
Plant Protection Products ◽  
Comparative Investigation ◽  
Negative Control ◽  
Genotoxic Activity ◽  
Technical Products ◽  
Dose Dependent Increase ◽  
Dose Dependent

Glyphosate is one of the most widely used herbicides in the world. In recent years, there have been concerns about the possible mutagenicity and carcinogenicity of this pesticide. In this connection, the study of genotoxic and carcinogenic properties of glyphosate and glyphosate-containing preparations has been resumed in a number of countries. In this study, the induction of micronucleation formation in vivo in polychromatophilic erythrocytes of bone marrow of CD-1 mice was assessed by the action of three different technical glyphosate products entering the Russian Federation. It was found that the tested samples of technical products showed different cytogenetic activity, while only one of them caused a statistically significant, dose-dependent increase in the frequency of induction of micronuclei compared to the negative control. The analysis of the composition of the studied product samples showed that the cytogenetic activity may depend on the content of potentially mutagenic impurities, in particular formaldehyde. The obtained data are additional grounds for lowering the upper limit of formaldehyde content in technical products of glyphosate and also indicate the need to assess the genotoxic activity of analog pesticides entering the market of plant protection products.

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