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Endocrine Disruptor Compounds (Edcs) and Agriculture: the Case of Pesticides Yves Combarnous Endocrine Disruptor Compounds (EDCs) and agriculture: The case of pesticides Yves Combarnous To cite this version: Yves Combarnous. Endocrine Disruptor Compounds (EDCs) and agriculture: The case of pesticides. Comptes Rendus Biologies, Elsevier Masson, 2017, 340 (9-10), pp.1-4. 10.1016/j.crvi.2017.07.009. hal-01605710 HAL Id: hal-01605710 https://hal.archives-ouvertes.fr/hal-01605710 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives| 4.0 International License C. R. Biologies 340 (2017) 406–409 Contents lists available at ScienceDirect Comptes Rendus Biologies w ww.sciencedirect.com Endocrine disruptors Endocrine Disruptor Compounds (EDCs) and agriculture: The case of pesticides a,b, Yves Combarnous * a INRA, CNRS, universite´ de Tours, UMR « Physiologie de la reproduction & des comportements », 37380 Nouzilly, France b Acade´mie d’agriculture de France, 75015 Paris, France A R T I C L E I N F O A B S T R A C T Article history: A number of pesticides are suspected or proved to act as endocrine disruptor compounds Received 29 November 2016 (EDCs). In the present survey of the literature, we try to define the main issues to be Accepted after revision 21 July 2017 considered to classify individual pesticides as EDC or not. Available online 18 August 2017 C 2017 Acade´mie des sciences. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ Keywords: 4.0/). Pesticide Endocrine Disruptor Nuclear receptor Risk Hazard Mechanism 1. Introduction Our aim in the present paper is to define the functional characteristics of endocrine disruptors in order to evaluate Pesticides are synthetic molecules aimed at being toxic if their toxicity toward non-target species is primarily due towards fungi, plants or animals that are detrimental to to endocrine disruption or not. cultures. Fungicides, herbicides, and insecticides have been developed in order to control as specifically as possible 2. Endocrine disruptors definition(s) these pests in order to protect cultures. Nevertheless, these pesticides can be toxic to Human and wild fauna. These Endocrine disruptor compounds (EDCs) have been molecules are intended to be toxic since they are aimed to defined in 2002 by the WHO: ‘‘An endocrine disruptor is destroy living organisms, but they are selected to affect an exogenous substance or mixture that alters function(s) precise steps in target organism(s) that are not present in of the endocrine system and consequently causes adverse non-target organisms. Also, their intended use is to acutely health effects in an intact organism, or its progeny, or eradicate unwanted species, and most toxicity tests are (sub)populations’’. also done in acute situations rather than in long-term The endocrine system is constituted by a large network experiments. And it is generally in long-term situations of hormones allowing the coordinate functions of dozens that xenogeneic molecules can potentially act as endocrine of different cell types in multicellular organisms. This disruptors. network possesses numerous loops of stimulation and retroaction in cascade so that the different physiological parameters (such as glycaemia, lipedema, hydro-mineral balances, etc.) and physiological functions (such as development, growth, reproduction, etc.) are set in the * INRA, CNRS, universite´ de Tours, UMR « Physiologie de la reproduction proper range for the good health of the whole organism & des comportements », 37380 Nouzilly, France. E-mail address: [email protected]. and for the survival of the species. http://dx.doi.org/10.1016/j.crvi.2017.07.009 C 1631-0691/ 2017 Acade´mie des sciences. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Y. Combarnous / C. R. Biologies 340 (2017) 406–409 407 Fig. 1. Mechanisms of action of Endocrine Disruptor Compounds (EDCs). A. Direct interaction of EDC with a hormone nuclear receptor leading to stimulation (agonism) or inhibition (antagonism) of its transcriptional activity. B. Stimulation or inhibition of endogeneous hormone biosynthesis. C. Stimulation or inhibition of endogeneous hormone degradation. D. Stimulation or inhibition of endogeneous hormone binding protein leading to decreased or enhanced circulating hormone availability. In this paper, our aim is to introduce a number of central The insecticides control insects by interfering with their questions concerning EDCs with particular interest in nervous system or by inhibiting their molt. For example, pesticides. acetylcholinesterase inhibitors (organophosphates, carba- mates) and sodium channel agonists (pyrethroids) act on 3. Endocrine disruption mechanisms the insect’s nervous system [8,9] as well as neonicotinoid insecticides (imidacloprid, acetamiprid, thiacloprid, clo- EDCs are molecules, natural or synthetic, that happen to thianidin, thiamethoxam, and dinotefuran) that act through interfere with the endocrine network of vertebrates, their preferential affinity for nicotinic receptor (nAChR) provoking adverse dysregulation of the hormonally subtypes [10–15]. The latter have favourable safety profiles, controlled physiological parameters or functions [1]. This due to their poor penetration of the mammalian blood– interference can occur through different mechanisms brain barrier and low application rates, and they effectively (Fig. 1) either directly by binding to the hormone receptor, control pest species that have evolved resistance to other or indirectly by increasing or decreasing the concentration insecticide classes. However, due to their high intrinsic of endogenous hormone(s): toxicity to honey bees [16,17], nitro-substituted neonico- tinoid insecticides have been intensively examined world- the most direct one is an interaction of the EDCs with an wide by regulatory agencies and temporarily suspended in hormone receptor leading either to stimulation (Fig. 1A) the European Union for seed treatment, soil application, and [2] or inhibition (Fig. 1A) of downstream cellular foliar treatment in crops attractive to bees. This illustrates pathway in target cells; the difficulty to develop and use insecticides without or endogenous active hormone concentrations can be affecting non-target insects [18,19]. affected by the stimulation or inhibition of either their The herbicides control development of unwanted synthesis (Fig. 1B), or degradation (Fig. 1C) [2,3], or plants by inhibiting synthesis of some of their amino- availability (Fig. 1D). acids or their photosynthesis or by specifically antagonizing the action of natural regulators of their development [20– A number of in vitro and in vivo tests have been set up by 22]. For example, triketone herbicides alter the formation of diverse national and international agencies to identify carotenoids and therefore disrupt the photosynthetic EDCs [4–7]. electron transport in plants. Since the aim is to have physiological impact on specific weeds and not on crops, the 4. Structures and intended toxic activity of pesticides rapid metabolism of triketones by maize, in particular by cytochrome P450 enzymes, makes this plant insensitive to A large majority of pesticides are small organic the herbicide treatment [23]. A precise knowledge of the molecules with molecular weights around 300 to 2000 Da. weed species is important to obtain maximum efficiency by 408 Y. Combarnous / C. R. Biologies 340 (2017) 406–409 choosing the most specific and efficient herbicide [24]. The molecules as thoroughly as possible in order to evaluate fungicides [25] control fungi by inhibiting the synthesis of the risk for human and/or wildlife populations. In this some of their amino-acids or their cell division. prospect, it is important to consider (1) the exposure of populations to the chemical under study, (2) the dose 5. Structures and endocrine-disrupting activity of responses of its effects, and (3) the cocktail effect. pesticides In the case of pesticides, it is clear that professional exposure [28] is considerably higher than the general Many in vitro tests have been set up to detect direct population’s exposure, but professionals can take appro- potential stimulating or inhibiting effects (Fig. 1A) of priate measures, if correctly informed, while the public pesticides on the transcriptional activity of nuclear should not be exposed to detrimental levels of pesticide(s). receptors, that are the main direct targets of EDCs Moreover, the prenatal and postnatal periods of develop- [26]. In 2010, a large survey of 200 pesticides in in vitro ment until puberty are particularly sensitive, because of transcriptional tests for six different receptors (hERa, their persistent effects due to possible detrimental effects hERb, hAR, hPXR, mPPARa, mAhR) was published [27], and during developmental steps [29]. The exposure of the pointed out that, among them, 47 showed hERa-mediated general
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