CONICET | Buscador de Institutos y Recursos Humanos

The environmental pollution caused by agrochemicals is an issue of increasing concern, mainly because the exposure to agrochemicals may cause health effects on non-target species, even far from application sites. The most widespread agrochemicals include organochlorine pesticides, glyphosate-based herbicides, atrazine, cypermethrin, and chlorpyrifos, among others. Although in some countries some of these chemicals have been banned, they persist both in the environment and in the food chain. Results from laboratory and field studies have reported that the exposure to agrochemicals at environmentally relevant concentrations affect the functioning of cells, organs and systems through changes at molecular, cellular and tissue levels. Besides, epidemiological data have shown associations between agrochemical exposure and increased hormone-dependent tumor incidence, impaired reproductive outcome, and obesity.This Special Issue on Health Effects of Agrochemicals as Endocrine Disruptors compiles eleven review articles written by some of the greatest experts in the domain. These reviews present the state of the art in the field and strong evidence that humans, farm animals and wildlife are exposed to low, environmentally relevant, levels of agrochemicals that would act as endocrine-disrupting compounds (EDCs) and that would thus be responsible for adverse effects on development, neurogenesis, fertility, obesity and neoplasia. The review by Warner et al. addresses the variety of mechanisms through which agrochemicals can act as EDCs. These authors summarize the mechanisms of action of agrochemicals involving the ability to mimic the interaction between endogenous hormones and nuclear receptors such as estrogen receptors, androgen receptors, peroxisome proliferator activated receptors, the aryl hydrocarbon receptor, and thyroid hormone receptors, as well as non-genomic mechanisms of action, including interference with peptide, steroid, or amino acid hormone response, synthesis and degradation and epigenetic changes. Meanwhile, the review by Vandenberg et al. describes several distinct ways in which the agrochemicals used in crop production can affect estrogen signaling and illustrates how screening tests such as the US EPA´s EDSP Tier 1 assays and World Health Organization´s criteria can be used to evaluate agrochemicals for endocrine activity. Three of the other reviews included in this Special Issue address the effects of agrochemicals in non-mammalian vertebrate species. The use of comparative approaches to study the effects of agrochemicals that act as EDCs is very important and impactful, because it helps to identify similarities and species-specific differences in hormones and their action, which are essential to choose and characterize animal models, to improve species survival, sustainability, and eco-health. The review by Martyniuk et al. describes the potent endocrine-disrupting properties of organochlorine pesticides in fish, whereas that by Trudeau et al. provides interesting data on agrochemical disruption of multiple endocrine axes in amphibians, on how metamorphosis can be either advanced or delayed by agrochemicals with consequences on juvenile and adult health and survival, and on how agrochemicals affect anuran sexual development, including sex reversal and intersex in several species. On the other hand, the review by Tavalieri et al. focuses on crocodilians as sentinels of wetland ecosystems and on the effects of the pesticides atrazine and endosulfan on the reproductive system of aquatic wildlife species.The other five reviews cover a broad spectrum of research in mammalian animal models across different organs and hormone-modulated processes. The review by Rossetti et al. focuses on the most commonly used agrochemicals in Argentina and their effects on hippocampal neurogenesis. These authors also discuss the disruption of hormone synthesis and action as a possible mechanism through which agrochemicals could alter the brain functions. The review by Kass et al. provides a very comprehensive summary on the endocrine-disrupting effects of agrochemical pesticides on the development and differentiation of the rodent mammary gland. These authors also discuss the relationship between pesticide body burden and breast cancer and the gaps in knowledge that still exist on male breast cancer. Milesi et al. provide an overview of the fate and levels of endosulfan in the environment and the human population, the potential estrogenic properties of endosulfan in vitro and in vivo, its effects on uterine development, and its long-term effects on rodent female fertility. Ingaramo et al. summarize the endocrine-disrupting effects of exposure to glyphosate and glyphosate-based herbicides at low -environmentally relevant- doses on female reproductive tissues affecting fertility. These authors highlight the limitations of in vitro assays and the advantages of using different animal models to show that the effects on the female reproductive tract may be related to the mechanisms of actions of an EDC. On the other hand, the review by Ren et al. provides data from experimental animal studies showing obesogenic effects of agrochemicals, such as on the development and transgenerational effects. These authors also provide considerable epidemiological evidence linking human exposure to agrochemicals with obesity. Finally, the review by Cardona & Rudel states that breast cancer risk from pesticides may be missed if effects on mammary gland are not assessed in toxicology studies required for registration. This topic is of current scientific and regulatory interest and suggests that several common pesticides should be re-evaluated since it is important that the effects caused by pesticides and other chemicals on the mammary gland be considered in risk assessment.We expect that the data provided by the eleven reviews included in this Special Issue make possible a deep discussion of the evidences on the mechanisms of action and effects of agrochemicals to clarify whether these compounds behave as EDCs at the low doses that pollute the environment and, if necessary, help to re-define the safe doses. We hope that researchers, conservationists and police makers will enjoy the reading and that the reviews here presented become a useful resource for their research activity and professional practice.We cannot end this Editorial without thanking the reviewers, and, of course, the authors, whose contributions have been immeasurable to the success of this Research Topic and who have made this Special Issue come true. We are also deeply thankful to Vincent Laudet for inviting us to be guest editors and for contributing to making this Special Issue a reality