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      Mixture toxicity assisting the design of eco-friendlier plant protection products: a case-study using a commercial herbicide combining nicosulfuron and terbuthylazine

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          Abstract

          The development of environmentally friendly plant protection products (PPPs), including pesticides, is a challenge nowadays. A commercial herbicide combining terbuthylazine and nicosulfuron as active substances (a.s.) was selected as a model PPP. The suitability of manipulating the ratio between a.s. towards alternative formulations with reduced impacts in a non-target indicator ( Lemna minor) was assessed. The efficacy of such eco-friendlier a.s. ratios was then assessed using a target weed, Portulaca oleracea. Single and mixture toxicity testing with L. minor revealed an antagonistic joint action of the a.s., suggesting an environmentally protective effect of the combination compared to single dosing of a.s. The efficacy testing against the target weed of single and combined treatments of the a.s. showed that (i) the a.s. behave antagonistically throughout the whole P. oleracea response surface; (ii) there were no environmentally safe a.s. combinations ensuring target-efficacy; (iii) terbuthylazine alone was effective in controlling P. oleracea with no environmental hazardous potential, dosed at concentrations 10-fold lower than those involved in commercially recommended application doses. Overall, this case-study suggests that modelling tools widely used in the field of environmental risk assessment of PPPs may also have application in PPP design stages for a more efficient meeting of efficacy and environmental friendliness requirements.

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          An international database for pesticide risk assessments and management

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            ‘Environmental and Economic Costs of the Application of Pesticides Primarily in the United States’

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              The expected effect of a combination of agents: the general solution.

              Interactions between agents (drugs, carcinogens, physiological stimuli, environmental pollutants, etc.) in producing their effects are of fundamental interest and practical importance in virtually every branch of biology and medicine. A combination of agents is said to show interaction when the magnitude of its effect is greater or smaller than expected, expectation being based on the dose-effect relations of the individual agents in the combination. The crux of the matter is to decide what is expected, and various rules have been proposed to this end (for example, that the expected effect is the sum of the effects of the individual constituents of the combination, or that it is the product of these effects, or that it may be calculated from the law of mass action). These rules are valid for combinations of agents with particular and rather restricted types of dose-effect relations, but they have no general validity. A general solution to this problem is given here, that enables the effects of non-interactive combinations to be calculated directly from the dose-effect relations of the individual agents (whether expressed algebraically or numerically), regardless of the particular types of dose-effect relations involved. This solution is based on the fact that, when an effect of particular magnitude is produced by a combination of n agents which do not interact to produce that effect, the point representing the combination in the n-dimensional space spanned by the dose-axes of the individual agents lies in the same (n-1)-dimensional hyperplane as those representing other combinations iso-effective with it and iso-effective amounts of the individual agents. Methods for calculating the effect of a non-interactive combination as the sum or product of the effects of its constituents, or from the law of mass action, each of which is correct in appropriate cases, may be deduced (without invoking mechanisms of action) by applying this general principle to particular types of dose-effect relations.
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                Author and article information

                Contributors
                jpereira@ua.pt
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 April 2018
                3 April 2018
                2018
                : 8
                : 5547
                Affiliations
                ISNI 0000000123236065, GRID grid.7311.4, Department of Biology, CESAM (Centre for Environmental and Marine Studies), , Campus de Santiago, ; 3810-193 Aveiro, Portugal
                Author information
                http://orcid.org/0000-0001-7573-6184
                Article
                23883
                10.1038/s41598-018-23883-5
                5883046
                29615770
                403d7d63-6cb6-4477-8d16-4829fbc18077
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 November 2017
                : 22 March 2018
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