Glyphosate is an endocrine disruptor and can act on the activity of certain enzymes of metabolism subsequently altering some functions such as reproduction. The goal of the present study is to evaluate the involvement of glyphosate based-herbicide (GBH) in spermatogenesis disruption and to investigate which cells of the adult Wistar rat testis are most affected by short-term exposure to GBH. Treated groups received a diluted solution of GBH orally for 21 days (D1: 102.5 mg/Kg; D2: 200 mg/Kg; D3: 400 mg/Kg). The control group (C) received water in the same manner. Hormone levels, oxidative stress markers were evaluated, histological and morphometric analysis were performed, AR and p53 expression was conducted. Seminiferious epithelium sloughing associated to erosion of Sertoli and spermatogonia from the basement of the seminiferous tubules, with intraluminal exfoliated cells among with immature spermatids were observed. A significant change in morphometric measurement and significant decrease in AR expression in Sertoli cells were noted for all treated groups. A significant increase in NO level and p53 expression in Leydig cells were showed for animals treated with 200 and 400 mg/kg BW/day. These data demonstrate that short-term exposure to high doses of GBH has led to a disruption of certain parameters that could disturb spermatogenesis. The treatment showed that both Leydig and Sertoli cells are affected in the same manner by GBH, the activation of p53 expression in both Leydig cells and peritubular myloid cells nuclei, and the reduction in AR expression in Sertoli cells, which resulted in important testicular damage.

The use of genetically modified, glyphosate-resistant crops has led to the widespread application of glyphosate-based herbicides (GBHs), making them one of the most widely used herbicide formulations on the market. To enhance the efficacy of the active ingredient, GBHs used in practice often contain other ingredients marked as inert \"adjuvants\" or \"co-formulants\", the toxic properties of which are poorly understood. The objective of this study was to compare the cytotoxic effects of pure glyphosate, three GBHs (Roundup Mega, Fozat 480 and Glyfos) and two co-formulants commonly used in GBHs as assessed via CCK-8 assay, and the extent of their potential oxidative damage as assessed via superoxide dismutase (SOD) assay, in order to reveal the role of adjuvants in the toxicity of the formulations. Our results showed that glyphosate alone did not significantly affect cell viability. In contrast, GBHs and adjuvants induced a pronounced cytotoxic effect from a concentration of 100 μM. SOD activity of cells treated with GBHs or adjuvants was significantly lower compared to cells treated with glyphosate alone. This suggests that the adjuvants in GBHs are responsible for the cytotoxic effects of the formulations through the induction of oxidative stress.

Introduction: Glyphosate is a widely used, non-selective herbicide. Glyphosate and glyphosate-based herbicides (GBHs) are considered safe for non-target organisms and environmentally benign at currently allowed environmental exposure levels. However, their increased use in recent years has triggered questions about possible adverse outcomes due to low dose chronic exposure in animals and humans. While the toxicity of GBHs has primarily been attributed to glyphosate, other largely unstudied components of GBHs may be inherently toxic or could act synergistically with glyphosate. Thus, comparative studies of glyphosate and GBHs are needed to parse out their respective toxicity. Methods: We performed such a comparative screen using pure glyphosate and two popular GBHs at the same glyphosate acid equivalent concentrations in the freshwater planarian Dugesia japonica. This planarian has been shown to be a useful model for both ecotoxicology and neurotoxicity/developmental neurotoxicity studies. Effects on morphology and various behavioral readouts were obtained using an automated screening platform, with assessments on day 7 and day 12 of exposure. Adult and regenerating planarians were screened to allow for detection of developmentally selective effects. Results: Both GBHs were more toxic than pure glyphosate. While pure glyphosate induced lethality at 1 mM and no other effects, both GBHs induced lethality at 316 μM and sublethal behavioral effects starting at 31.6 μM in adult planarians. These data suggest that glyphosate alone is not responsible for the observed toxicity of the GBHs. Because these two GBHs also include other active ingredients, namely diquat dibromide and pelargonic acid, respectively, we tested whether these compounds were responsible for the observed effects. Screening of the equivalent concentrations of pure diquat dibromide and pure pelargonic acid revealed that the toxicity of either GBH could not be explained by the active ingredients alone. Discussion: Because all compounds induced toxicity at concentrations above allowed exposure levels, our data indicates that glyphosate/GBH exposure is not an ecotoxicological concern for D. japonica planarians. Developmentally selective effects were not observed for all compounds. Together, these data demonstrate the usefulness of high throughput screening in D. japonica planarians for assessing various types of toxicity, especially for comparative studies of several chemicals across different developmental stages.

Glyphosate herbicide is ubiquitously used in agriculture and weed control. It has now been identified in aquatic ecosystems worldwide, where numerous studies have suggested that it may have both suppressive and stimulatory effects on diverse non-target organisms. We cultured natural biofilms from a hypereutrophic environment to test the effects on periphytic diatoms of exposure to a glyphosate-based herbicide formulation at concentrations from 0 to 10 mg L-1 of active ingredient. There were clear and significant differences between treatments in diatom community structure after the 15-day experiments. Diversity increased more in low glyphosate treatments relative to higher concentrations, and compositional analyses indicated statistically significant differences between glyphosate treatments. The magnitude of change observed was significantly correlated with glyphosate-based herbicide concentration. Our results show that glyphosate-based herbicides have species-selective effects on benthic diatoms that may significantly alter trajectories of community development and therefore may affect benthic habitats and whole ecosystem function.

Glyphosate-based herbicides, the most extensively used herbicides in the world, are available in an enormous number of commercial formulations with varying additives and adjuvants. Here, we study the effects of one such formulation, Credit41, in two genetically diverse yeast strains. A quantitative trait loci (QTL) analysis between a sensitive laboratory strain and a resistant strain linked mitochondrial function to Credit41 resistance. Two genes encoding mitochondrial proteins identified through the QTL analysis were HFA1, a gene that encodes a mitochondrial acetyl CoA carboxylase, and AAC3, which encodes a mitochondrial inner membrane ATP/ADP translocator. Further analysis of previously studied whole-genome sequencing data showed that, although each strain uses varying routes to attain glyphosate resistance, most strains have duplications of mitochondrial genes. One of the most well-studied functions of the mitochondria is the assembly of Fe-S clusters. In the current study, the expression of iron transporters in the transcriptome increased in cells resistant to Credit41. The levels of iron within the cell also increased in cells exposed to Credit41 but not pure glyphosate. Hence, the additives in glyphosate-based herbicides have a significant contribution to the negative effects of these commercial formulations on biological systems.

The aim of this work was to know the differential composition of the dissolved fraction of a glyphosate-based herbicide (GBH), commercialized as GLIFOPAC, when reaches different aquatic environments and its ecotoxicological effects on crustaceans species living in them. Daphnia magna, Tisbe longicornis, and Emerita analoga were exposed to glyphosate herbicide called GLIFOPAC (480 g L-1 of active ingredient or a.i.) at concentrations between 0.5 and 4.8 g a.i. L-1. Acute toxicity in D. magna (48 h-LC50), E. analoga (48 h-LC50), and T. longicornis (96 h-LC50) was studied. Chromatographic analysis of the GBH composition used and water (freshwater/sea water) polluted with GLIFOPAC were evaluated. Results reported acute toxicity (48-96 h-LC50) values for D. magna, E. analoga and T. longicornis of 27.4 mg L-1, 806.4 mg L-1, and 19.4 mg L-1, respectively. Chromatographic evaluation described around 45 substances of the GLIFOPAC composition, such as from the surfactant structures (aliphatic chain with esther/ether group), metabolites (AMPA), and other substances (glucofuranose, glucopyranoside, galactopyranose). This study evidenced differences in the GLIFOPAC composition in freshwater and marine water, which may differentiate the toxic response at the crustacean-level in each aquatic environment.

Glyphosate, formulated as Roundup, is the world\'s most widely used herbicide. Glyphosate is used extensively on genetically modified (GM) food crops designed to tolerate the herbicide, and global use is increasing rapidly. Two recent reviews of glyphosate\'s health hazards report conflicting results. An independent review by the International Agency for Research on Cancer (IARC) found that glyphosate is a \"probable human carcinogen\". A review by the European Food Safety Agency (EFSA) found no evidence of carcinogenic hazard. These differing findings have produced regulatory uncertainty.
Reflecting this regulatory uncertainty, the European Commission on November 27 2017, extended authorization for glyphosate for another 5 years, while the European Parliament opposed this decision and issued a call that pesticide approvals be based on peer-reviewed studies by independent scientists rather than on the current system that relies on proprietary industry studies.
The Ramazzini Institute has initiated a pilot study of glyphosate\'s health hazards that will be followed by an integrated experimental research project. This evaluation will be independent of industry support and entirely sponsored by worldwide crowdfunding. The aim of the Ramazzini Institute project is to explore comprehensively the effects of exposures to glyphosate-based herbicides at current real-world levels on several toxicological endpoints, including carcinogenicity, long-term toxicity, neurotoxicity, endocrine disrupting effects, prenatal developmental toxicity, the microbiome and multi-generational effects.

Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine.
We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA.
Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA.
Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.

Eating, drinking, sexual activity, and parenting invoke pleasure, an emotion that promotes repetition of these behaviors, are essential for survival. Euphoria, a feeling or state of intense excitement and happiness, is an amplification of pleasure, aspired to one\'s essential biological needs that are satisfied. People use party drugs as a shortcut to euphoria. Ecstasy (3,4-methylenedioxymethamphetamine), γ-hydroxybutyric acid, and ketamine fall under the umbrella of the term \"party drugs,\" each with differing neuropharmacological and physiological actions. This chapter seeks to survey the history and epidemiology of party drug use; we will then discuss the pharmacological characteristics of each drug to provide a platform for understanding the difficulties that party drug users encounter through intoxication, harmful use, dependence, and withdrawal and how these should be clinically managed.