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      A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

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          Abstract

          The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin doramectin and moxidectin. By comparison, information on compounds such as eprinomectin, emamectin and selamectin is still relatively scarce.

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          Microbial drug discovery: 80 years of progress

          Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.
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            Avermectins, new family of potent anthelmintic agents: producing organism and fermentation.

            The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 mug/ml.
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              Ivermectin: a potent new antiparasitic agent.

              Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet known whether ivermectin will be useful in human medicine.
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                Author and article information

                Journal
                Curr Pharm Biotechnol
                Curr Pharm Biotechnol
                CPB
                Current Pharmaceutical Biotechnology
                Bentham Science Publishers
                1389-2010
                1873-4316
                May 2012
                May 2012
                : 13
                : 6
                : 1004-1060
                Affiliations
                [1 ]UMR 5175 CEFE, Zoogéographie, Université Montpellier III, 34199 Montpellier cedex 5, France
                [2 ]UR Biodiversité et Biologie des Populations, ISSBAT, 9 ave Zohair Essefi, 1007, Tunis, Tunisia
                [3 ]Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, Alberta, Canada, T1J 4B1
                [4 ]ECT Oekotoxikologie GmbH, Böttgerstrasse 2-14, D-65439 Flörsheim, Germany
                [5 ]11 Deane Street, Yarralumla, Canberra, ACT 2600, Australia
                Author notes
                [* ]Address correspondence to this author at the UMR 5175 CEFE, Laboratoire de Zoogéographie, Université Montpellier III, 34199 Montpellier cedex 5, France; Tel: (+33) 4 67 14 23 16; Fax: (+33) 4 67 14 24 59; E-mail: jean-pierre.lumaret@ 123456univ-montp3.fr
                Article
                CPB-13-1004
                10.2174/138920112800399257
                3409360
                22039795
                b8b8ba00-61b7-46c0-9f17-7b99bf162614
                © 2012 Bentham Science Publishers

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 January 2010
                : 21 December 2010
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                abamectin,spinosad,ivermectin,veterinary pharmaceuticals.,eprinomectin,moxidectin (milbemycin),endectocides,emamectin benzoate,doramectin,ecotoxicology

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