Toxicokinetic mixture effects of co-formulants and active substances in plant protection products in vitro

2021 ◽  
Vol 350 ◽  
pp. S237
Author(s):  
M. Karaca ◽  
B. Fischer ◽  
C.T. Willenbockel ◽  
P. Marx-Stoelting ◽  
D. Bloch
Author(s):  
Mawien Karaca ◽  
Benjamin Christian Fischer ◽  
Christian Tobias Willenbockel ◽  
Tewes Tralau ◽  
Philip Marx-Stoelting ◽  
...  

AbstractCurrently, the authorisation process for plant protection products (PPPs) relies on the testing of acute and topological toxicity only. Contrastingly, the evaluation of active substances includes a more comprehensive set of toxicity studies. Nevertheless, mixture effects of active ingredients and co-formulants may result in increased toxicity. Therefore, we investigated effects of surface active co-formulants on the toxicity of two PPPs focussing on qualitative and quantitative toxicokinetic effects on absorption and secretion. The respective products are based on the active substances abamectin and fluroxypyr-meptyl and were tested for cytotoxicity in the presence or absence of the corresponding surfactants and co-formulants using Caco-2 cells. In addition, the effect of co-formulants on increased cellular permeation was quantified using LC–MS/MS, while potential kinetic mixture effects were addressed by fluorescence anisotropy measurements and ATPase assays. The results show that surface active co-formulants significantly increase the cytotoxicity of the investigated PPPs, leading to more than additive mixture effects. Moreover, analytical investigations show higher efflux ratios of both active substances and the metabolite fluroxypyr upon combination with certain concentrations of the surfactants. The results further point to a significant and concentration-dependent inhibition of Pgp transporters by most of the surfactants as well as to increased membrane fluidity. Altogether, these findings strongly support the hypothesis that surfactants contribute to increased cytotoxicity of PPPs and do so by increasing the bioavailability of the respective active substances.


2014 ◽  
Vol 9 (2) ◽  
pp. 157-166 ◽  
Author(s):  
Dorothee J. Lüken ◽  
Martina Janke ◽  
Friedrich-Wilhelm Lienau ◽  
Katharina Gerdel ◽  
Werner von der Ohe ◽  
...  

2021 ◽  
Vol 3 ◽  
Author(s):  
Rositsa Serafimova ◽  
Tamara Coja ◽  
George E. N. Kass

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.


2015 ◽  
Vol 76 (2) ◽  
pp. 191-206 ◽  
Author(s):  
Adam Okorski ◽  
Agnieszka Pszczółkowska ◽  
Tomasz Oszako ◽  
Justyna A. Nowakowska ◽  
Małgorzata Oszako

AbstractThe possibility of using chemicals in European forestry is extremely limited due to the binding legal regulations and specific conditions concerning the market of plant protection products. This is reflected in the limited availability of active fungicides in forestry. Due to this limitation, practitioners using fungicides in forest nurseries and forest cultivation must have substantial knowledge of the biology of pathogens to ensure satisfactorily effective protection.The work presented here provides an overview of the currently recommended fungicides in Polish forestry as well as the mechanisms of interaction between the active substances and the pathogen, the plant and mycorrhizal fungi. The risk of fungicide resistance, which has been insufficiently explored in the context of forest pathogens, is also discussed in this paper.


2020 ◽  
Author(s):  
Aude Ratier ◽  
Christelle Lopes ◽  
Gauthier Multari ◽  
Vanessa Mazerolles ◽  
Patrice Carpentier ◽  
...  

AbstractToday, there are no ready-to-use convenient tools in ecotoxicology to diagnose and predict the accumulation and effects of chemical substances on living organisms, accounting for exposure situations that are known to be complex (routes of exposure, metabolization processes, cocktail effects, etc.). Regarding plant protection products in marketing authorization applications, regulation No 283/2013 (EU) defines the data requirements for active substances with a bioaccumulation test on fish according to OECD Test guideline 305. This paper presents new perspectives on the estimation of the bioaccumulation factors via an innovative ready-to-use web tool providing these factors, associated with their uncertainty to facilitate the daily work of regulators, but also of any user, by benefiting of a freely available and user-friendly on-line interface avoiding to invest into underlying mathematical and statistical technicalities. This tool, MOSAICbioacc, is available at https://mosaic.univ-lyon1.fr/bioacc, and can be used by any environmental scientists, ecotoxicologists or managers when accumulation-depuration data are collected and need to be easily and quickly analysed.


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