Hormesis, the Individual and Combined Phytotoxicity of the Components of Glyphosate-Based Formulations on Algal Growth and Photosynthetic Activity.

The occurrence of the market-leading glyphosate active ingredient in surface waters is a globally observed phenomenon. Although co-formulants in pesticide formulations were considered inactive components from the aspects of the required main biological effect of the pesticide, several studies have proven the high individual toxicity of formulating agents, as well as the enhanced combined toxicity of the active ingredients and other components. Since the majority of active ingredients are present in the form of chemical mixtures in our environment, the possible combined toxicity between active ingredients and co-formulants is particularly important. To assess the individual and combined phytotoxicity of the components, glyphosate was tested in the form of pure active ingredient (glyphosate isopropylammonium salt) and herbicide formulations (Roundup Classic and Medallon Premium) formulated with a mixture of polyethoxylated tallow amines (POEA) or alkyl polyglucosides (APG), respectively. The order of acute toxicity was as follows for Roundup Classic: glyphosate < herbicide formulation < POEA. However, the following order was demonstrated for Medallon Premium: herbicide formulation < glyphosate < APG. Increased photosynthetic activity was detected after the exposure to the formulation (1.5-5.8 mg glyphosate/L and 0.5-2.2 mg POEA/L) and its components individually (glyphosate: 13-27.2 mg/L, POEA: 0.6-4.8 mg/L), which indicates hormetic effects. However, decreased photosynthetic activity was detected at higher concentrations of POEA (19.2 mg/L) and Roundup Classic (11.6-50.6 mg glyphosate/L). Differences were demonstrated in the sensitivity of the selected algae species and, in addition to the individual and combined toxicity of the components presented in the glyphosate-based herbicides. Both of the observed inhibitory and stimulating effects can adversely affect the aquatic ecosystems and water quality of surface waters.

Regulating seafarers' welfare: an examination of the protection of Filipino seafarers' well-being through a legal analysis of the POEA-Standard Employment Contract.

BACKGROUND: The Philippines is the global maritime industry's single biggest source of seafarers. This article examines how the Philippines protects the welfare of its seafarers working on board ocean-going vessels. MATERIALS AND METHODS: We employed a multi-method approach to better understand the POEA-SEC as a regulatory instrument. First, we analysed Philippine legislation and regulations that are shaping the employment, welfare, and working conditions of Filipino seafarers. Second, we examined the Philippine Overseas Employment Administration Standard Employment Contract (POEA-SEC) which requires that minimum standards of employment for seafarers are met. We use legal analysis to examine three specific provisions that pertain to their well-being: duration of employment, monetary considerations, and working conditions in terms of hours of work and rest periods. Third, we analysed interview and focus group data on the experiences of Filipino seafarers on board ships in respect of the POEA-SEC's efficacy in protecting their well-being. RESULTS: Analysis of the policy environment for Filipino seafarers shows how the interests of powerful actors have taken precedence over those of Filipino seafarers. Seafarers' experiences suggest that they cannot be reached by the contract, whether symbolic or otherwise. The contract fails to address seafarer issues, such as security of tenure, excessive working hours resulting in fatigue, stress and anxiety. CONCLUSIONS: The POEA-SEC falls short as a legal document to address occupational, health and safety issues, which contribute to the detriment of seafarers' health and well-being. This indicates that the Philippine government cannot fully protect its seafarers.

Polyoxyethylene tallow amine and glyphosate exert different developmental toxicities on human pluripotent stem cells-derived heart organoid model.

The early stage of heart development is highly susceptible to various environmental factors. While the use of animal models has aided in identifying numerous environmental risk factors, the variability between species and the low throughput limit their translational potential. Recently, a type of self-assembling cardiac structures, known as human heart organoids (hHOs), exhibits a remarkable biological consistency with human heart. However, the feasibility of hHOs for assessing cardiac developmental risk factors remains unexplored. Here, we focused on the cardiac developmental effects of core components of Glyphosate-based herbicides (GBHs), the most widely used herbicides, to evaluate the reliability of hHOs for the prediction of possible cardiogenesis toxicity. GBHs have been proven toxic to cardiac development based on multiple animal models, with the mechanism remaining unknown. We found that polyoxyethylene tallow amine (POEA), the most common surfactant in GBHs formulations, played a dominant role in GBHs' heart developmental toxicity. Though there were a few differences in transcriptive features, hHOs exposed to sole POEA and combined POEA and Glyphosate would suffer from both disruption of heart contraction and disturbance of commitment in cardiomyocyte isoforms. By contrast, Glyphosate only caused mild epicardial hyperplasia. This study not only sheds light on the toxic mechanism of GBHs, but also serves as a methodological demonstration, showcasing its effectiveness in recognizing and evaluating environmental risk factors, and deciphering toxic mechanisms.

Negligible Toxicokinetic Differences of Glyphosate by Different Vehicles in Rats.

Glyphosate is a non-selective herbicide. Although glyphosate is not acutely toxic, the intake of glyphosate-based herbicides has caused many accidents. Some studies have suggested that surfactants might be the cause. The purpose of this study was to compare the toxicokinetic (TK) properties of glyphosate according to different vehicles in rats. Glyphosate (1%) was dissolved in distilled water (DW), polyoxyethylene tallow amine (POEA), and Tween 20. After a single oral treatment of glyphosate (50 mg/kg), blood was collected at time intervals, and glyphosate concentrations in the target organ (liver and kidney) were determined 24 h after final blood collection. All samples were analyzed using LC-MS/MS. The TK parameters of glyphosate were similar in the DW and Tween 20 groups. However, there were significant differences in Tmax and volume of distribution (Vd) between the DW and POEA group (p < 0.05). Glyphosate was absorbed about 10 times faster in POEA group rather than DW, and exhibited a higher distribution. However, other important TK parameters of T1/2, AUC, and Cmax were not statistically different among the different vehicle groups. Although glyphosate concentration in the liver was significantly higher in the POEA group than in the DW group, there was no significant difference in the kidney. These results indicate that the toxicokinetics of glyphosate are not significantly affected by POEA. It can be concluded that POEA toxicity itself can be attributed to the acute toxicity of glyphosate-containing products.

Environmental fate studies with 14C-polyoxyethylene tallow amine (POE-T) to characterize environmental exposure and inform environmental risk assessments.

Polyoxyethylene tallow amine (POE-T) is a member of the polyoxyethylene alkylamine (POEA) class of nonionic surfactants and is a component of some glyphosate-based formulations. The presence of POE-T improves foliar uptake of glyphosate in weeds, thereby reducing the amount of glyphosate needed for weed control. To further characterize the environmental fate of POE-T, aerobic soil degradation, hydrolysis, adsorption/desorption, and aerobic aquatic degradation studies were conducted according to U.S. EPA and OECD pesticide regulatory testing guidelines. POE-T labeled with carbon-14 was used in the studies to aid in analysis, assess mineralization to CO2, and allow for mass balance determinations. The aerobic soil half-lives (DT50) for POE-T ranged from 20 to 166 days with DT50 values increasing with increasing soil percent organic carbon (OC). POE-T was hydrolytically stable at pH 4-9. POE-T adsorbed strongly to soil (KFocads = 17,600-114,000) with sorption generally increasing as soil percent OC increased. The aerobic aquatic (water-sediment) system DT50s for POE-T were 14-29 days, with POE-T dissipating from the water column with DT50s of 0.10-0.12 days through metabolism and adsorption to sediment. Based on these results, aquatic organisms are unlikely to be exposed to POE -T in the water column for more than a few hours following waterborne exposure and sediment is a significant sink for POE-T in aquatic systems. However, bioavailability of POE-T in sediment and soil is predicted to be low based on strong adsorption and it is not readily desorbed.

Dietary Behavior of Drosophila melanogaster Fed with Genetically-Modified Corn or Roundup®.

With the rise in concern about GMOs and pesticides on human health, we have utilized Drosophila melanogaster as a model organism for understanding the effects of Roundup-Ready® GMO diets on health. We recorded dietary behavior during and after exposure to a medium containing GMO or non-GMO corn, Roundup® in organic corn medium, and sucrose with or without one of the two Roundup® formulations. No differences in behavior were observed when Drosophila were exposed to a medium containing Roundup-Ready® GMO or non-GMO corn. Drosophila can detect and refrain from eating sucrose containing one Roundup® formulation, Ready-to-Use, which contains pelargonic acid in addition to glyphosate as an active ingredient. Drosophila exhibited dose-dependent increased consumption of sucrose alone after exposure to a medium containing either Roundup® formulation. This may indicate that flies eating a medium with Roundup® eat less and were thus hungrier when then given sucrose solution; that a medium with Roundup® is more difficult to digest; or that a medium with Roundup® is less nutritious, as would be the case if nutritionally important microbes grew on control medium, but not one containing Roundup®.

Ecotoxicology of Glyphosate, Its Formulants, and Environmental Degradation Products.

The chemical and biological properties of glyphosate are key to understanding its fate in the environment and potential risks to non-target organisms. Glyphosate is polar and water soluble and therefore does not bioaccumulate, biomagnify, or accumulate to high levels in the environment. It sorbs strongly to particles in soil and sediments and this reduces bioavailability so that exposures to non-target organisms in the environment are acute and decrease with half-lives in the order of hours to a few days. The target site for glyphosate is not known to be expressed in animals, which reduces the probability of toxicity and small risks. Technical glyphosate (acid or salts) is of low to moderate toxicity; however, when mixed with some formulants such as polyoxyethylene amines (POEAs), toxicity to aquatic animals increases about 15-fold on average. However, glyphosate and the formulants have different fates in the environment and they do not necessarily co-occur. Therefore, toxicity tests on formulated products in scenarios where they would not be used are unrealistic and of limited use for assessment of risk. Concentrations of glyphosate in surface water are generally low with minimal risk to aquatic organisms, including plants. Toxicity and risks to non-target terrestrial organisms other than plants treated directly are low and risks to terrestrial invertebrates and microbial processes in soil are very small. Formulations containing POEAs are not labeled for use over water but, because POEA rapidly partitions into sediment, risks to aquatic organisms from accidental over-sprays are reduced in shallow water bodies. We conclude that use of formulations of glyphosate under good agricultural practices presents a de minimis risk of direct and indirect adverse effects in non-target organisms.

Adjuvant contributes Roundup's unexpected effects on A549 cells.

Roundup® (RDP) is one of the most representative glyphosate-based herbicides (GBHs), which extensive use increases pressure on environmental safety and potential human health risk. The aim of this study was to investigate whether the adjuvant polyethoxylated tallow amine (POEA) or the herbicidal active ingredient glyphosate isopropylamine salt (GP) in formulation confers RDP cytotoxicity. We demonstrated that RDP and POEA could inhibit the proliferation of human lung A549 cells. Intracellular biochemical assay indicated that collapse of mitochondrial membrane, release of cytochrome c into cytosol, activation of caspase-9/-3, cleavage of poly (ADP-ribose) polymerase (PARP), oxidative DNA damage, DNA single-strand breaks and double-strand breaks are occurred in RDP and POEA treated A549 cells, not occurred in GP treated A549 cells. We conclude that the RDP's effect of apoptosis and DNA damage on human A549 cells is related to the presence of adjuvant POEA in formulation, independent of the herbicidal active ingredient GP. This study would enrich the theoretical basis of the RDP toxicity effects and attract attention on potential human health and environmental safety threat caused by adjuvant.

Controversies over human health and ecological impacts of glyphosate: Is it to be banned in modern agriculture?

Glyphosate, introduced by Monsanto Company under the commercial name Roundup in 1974, became the extensively used herbicide worldwide in the last few decades. Glyphosate has excellent properties of fast sorption in soil, biodegradation and less toxicity to nontarget organisms. However, glyphosate has been reported to increase the risk of cancer, endocrine-disruption, celiac disease, autism, effect on erythrocytes, leaky-gut syndrome, etc. The reclassification of glyphosate in 2015 as 'probably carcinogenic' under Group 2A by the International Agency for Research on Cancer has been broadly circulated by anti-chemical and environmental advocacy groups claiming for restricted use or ban of glyphosate. In contrast, some comprehensive epidemiological studies involving farmers with long-time exposure to glyphosate in USA and elsewhere coupled with available toxicological data showed no correlation with any kind of carcinogenic or genotoxic threat to humans. Moreover, several investigations confirmed that the surfactant, polyethoxylated tallow amine (POEA), contained in the formulations of glyphosate like Roundup, is responsible for the established adverse impacts on human and ecological health. Subsequent to the evolution of genetically modified glyphosate-resistant crops and the extensive use of glyphosate over the last 45 years, about 38 weed species developed resistance to this herbicide. Consequently, its use in the recent years has been either restricted or banned in 20 countries. This critical review on glyphosate provides an overview of its behaviour, fate, detrimental impacts on ecological and human health, and the development of resistance in weeds and pathogens. Thus, the ultimate objective is to help the authorities and agencies concerned in resolving the existing controversies and in providing the necessary regulations for safer use of the herbicide. In our opinion, glyphosate can be judiciously used in agriculture with the inclusion of safer surfactants in commercial formulations sine POEA, which is toxic by itself is likely to increase the toxicity of glyphosate.

An integrated transcriptomic- and proteomic-based approach to evaluate the human skin sensitization potential of glyphosate and its commercial agrochemical formulations.

We investigated the skin sensitization hazard of glyphosate, the surfactant polyethylated tallow amine (POEA) and two commercial glyphosate-containing formulations using different omics-technologies based on a human dendritic cell (DC)-like cell line. First, the GARD™skin assay, investigating changes in the expression of 200 transcripts upon cell exposure to xenobiotics, was used for skin sensitization prediction. POEA and the formulations were classified as skin sensitizers while glyphosate alone was classified as a non-sensitizer. Interestingly, the mixture of POEA together with glyphosate displayed a similar sensitizing prediction as POEA alone, indicating that glyphosate likely does not increase the sensitizing capacity when associated with POEA. Moreover, mass spectrometry analysis identified differentially regulated protein groups and predicted molecular pathways based on a proteomic approach in response to cell exposures with glyphosate, POEA and the glyphosate-containing formulations. Based on the protein expression data, predicted pathways were linked to immunologically relevant events and regulated proteins further to cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. In summary, we here present an integrative analysis involving advanced technologies to elucidate the molecular mechanisms behind DC activation in the skin sensitization process triggered by the investigated agrochemical materials. SIGNIFICANCE: The use of glyphosate has increased worldwide, and much effort has been made to improve risk assessments and to further elucidate the mechanisms behind any potential human health hazard of this chemical and its agrochemical formulations. In this context, omics-based techniques can provide a multiparametric approach, including several biomarkers, to expand the mechanistic knowledge of xenobiotics-induced toxicity. Based on this, we performed the integration of GARD™skin and proteomic data to elucidate the skin sensitization hazard of POEA, glyphosate and its two commercial mixtures, and to investigate cellular responses more in detail on protein level. The proteomic data indicate the regulation of immune response-related pathways and proteins associated with cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. Therefore, our data show the applicability of a multiparametric integrated approach for the mechanism-based hazard evaluation of xenobiotics, eventually complementing decision making in the holistic risk assessment of chemicals regarding their allergenic potential in humans.

Estimated exposure to glyphosate in humans via environmental, occupational, and dietary pathways: an updated review of the scientific literature.

Glyphosate is one of the most widely used herbicides in the world, but it has also been the focus of discussion and restrictions in several countries since it was declared 'probably carcinogenic to humans (Group 2A)' by the International Agency for Research on Cancer in 2015. Since that time, several regulatory agencies have reviewed the public literature and guideline studies submitted for regulatory purposes and have concluded that it is not a carcinogen, and revised acceptable daily intakes (ADIs) and the reference dose (RfD) have been published. Also, restrictions on use have been lifted in many locations. Risk assessment for any pesticide requires knowledge of exposure in humans and the environment, and this paper is an update on a previous review in 2016 and includes papers published after 2016. These exposure data for air, water, bystanders, the general public, domesticated animals, pets, and applicators were combined and compared to the revised exposure criteria published by regulatory agencies. In all cases, measured and estimated systemic exposures to glyphosate in humans and animals were less than the ADIs and the RfD. Based on this large dataset, these exposures represent a de minimis risk. © 2019 Society of Chemical Industry.

The surfactant polyethoxylated tallowamine (POEA) reduces lifespan and inhibits fecundity in Drosophila melanogaster- In vivo and in vitro study.

In order to develop an understanding of the role of adjuvants in a popular glyphosate-based herbicide - Roundup® Concentrate Plus (RCP), on non-target organisms, the effects of pure glyphosate [N-(phosphonomethyl)-glycine], RCP and a non-ionic surfactant - polyethoxylated tallowamine (POEA) were studied in the fruit fly Drosophila melanogaster. Acute exposure to sub-lethal concentrations of RCP (15 µg/mL) and POEA (45 µg/mL) reduced (p < 0.001) lifespan of female flies compared to untreated controls or glyphosate (100 µg/mL). Negative geotaxis responses in female flies were reduced (p < 0.05) following acute exposure to sub-lethal concentrations of RCP and POEA whereas glyphosate did not significantly affect this response compared to untreated flies. Acute exposure to sub-lethal concentrations of RCP and POEA elevated (p < 0.05) protein carbonyl levels while markedly (p < 0.01) inhibiting carbonyl reductase activity whereas glyphosate treatment did not significantly affect protein carbonyl levels or carbonyl reductase activity. Fecundity was reduced (p < 0.05) following exposure to sub-lethal concentrations of RCP and POEA whereas glyphosate did not affect fecundity. In vitro treatment of ovarian stem sheath (OSS) cells with sub-lethal concentrations of RCP and POEA revealed decreased cell viability and enhanced caspase activity indicative of pro-apoptotic processes after 48 h compared to untreated controls. Glyphosate however was non-toxic at the concentration used. The results suggest that RCP and the surfactant POEA are more toxic than pure glyphosate and inhibit fecundity in Drosophila by impairing cell viability through enhanced apoptosis.

Roundup-Induced AMPK/mTOR-Mediated Autophagy in Human A549 Cells.

The extensive use of pesticide caused an amount of pressure on the environment and increased the potential human health risk. Glyphosate-based herbicide (GBH) is one of the most widely used pesticides based on a 5-enolpyruvylshikimate-3-phosphate synthase target, which does not exist in vertebrates. Here, we study autophagic effects of the most famous commercial GBH Roundup (RDP) on human A549 cells in vitro. Intracellular biochemical assay indicated opening of mitochondrial permeability transition pore, LC3-II conversion, up-regulation of beclin-1, down-regulation of p62, and the changes in the phosphorylation of AMPK and mTOR induced by RDP in A549 cells. Further experimental results indicated that all the effects induced by RDP were related to its adjuvant polyethoxylated tallow amine, not its herbicidal active ingredient glyphosate isopropylamine salt. All these results showed that RDP has the ability to induce AMPK/mTOR-mediated cell autophagy in human A549 cells. This study would provide a theoretical basis for understanding RDP's autophagic effects on human A549 cells and attract attention on the potential human health risks induced by the adjuvant.

Toxicology and human health risk assessment of polyethoxylated tallow amine surfactant used in glyphosate formulations.

Roundup® branded herbicides contain glyphosate, a surfactant system and water. One of the surfactants used is polyethoxylated tallow amine (POE-T). A toxicology dataset has been developed to derive the most representative points of departure for human health risk assessments. Concentrated POE-T was very irritating to skin, corrosive to eyes, and sensitizing to skin. The irritation and sensitization potential of POE-T diminishes significantly upon dilution with water. Repeated dosing of rats with POE-T produced gastrointestinal effects but no systemic effect on organ systems. POE-T was not genotoxic and had no effect on embryo-fetal development or reproduction. The occupational risk assessment of POE- T for the agricultural use of glyphosate products has demonstrated that margins of exposure (MOEs) are 2517 and 100,000 for maximum and geometric mean dermal exposures, respectively. In the food risk assessment for relevant agricultural uses, the range of MOEs for consumption of foods from plant and animal origin were 330 to 2909. MOEs ≥100 are generally considered to be of no toxicological concern. Based on the results of the occupational and food risk assessments, it is concluded that there are no significant human health issues associated with the use of POE-T as a surfactant in glyphosate products.

Insight into the confusion over surfactant co-formulants in glyphosate-based herbicides.

Glyphosate is the active ingredient in glyphosate-based herbicides (GBHs). Other chemicals in GBHs are presumed as inert by regulatory authorities and are largely ignored in pesticide safety evaluations. We identified the surfactants in a cross-section of GBH formulations and compared their acute toxic effects. The first generation of polyethoxylated amine (POEA) surfactants (POE-tallowamine) in Roundup are markedly more toxic than glyphosate and heightened concerns of risks to human health, especially among heavily-exposed applicators. Beginning in the mid-1990s, first-generation POEAs were progressively replaced by other POEA surfactants, ethoxylated etheramines, which exhibited lower non-target toxic effects. Lingering concern over surfactant toxicity was mitigated at least in part within the European Union by the introduction of propoxylated quaternary ammonium surfactants. This class of POEA surfactants are ∼100 times less toxic to aquatic ecosystems and human cells than previous GBH-POEA surfactants. As GBH composition is legally classified as confidential commercial information, confusion concerning the identity and concentrations of co-formulants is common and descriptions of test substances in published studies are often erroneous or incomplete. In order to resolve this confusion, laws requiring disclosure of the chemical composition of pesticide products could be enacted. Research to understand health implications from ingesting these substances is required.

Dissipation of polyoxyethylene tallow amine (POEA) and glyphosate in an agricultural field and their co-occurrence on streambed sediments.

The environmental fate of polyoxyethylene tallow amine (POEA), an additive in glyphosate herbicide formulations, has not been studied. This study examined the dissipation of POEA; glyphosate; and aminomethylphosphonic acid (AMPA), a degradation product of glyphosate, in the top 45 cm of soil from an agricultural field where glyphosate was applied. The concentration of these compounds was also analyzed in bed sediment samples from watersheds in agricultural and urban areas from six states (Georgia, Hawaii, Iowa, Mississippi, North Carolina, South Carolina). The field studies show that POEA, glyphosate, and AMPA persist on the soil from planting season to planting season but dissipate over time with little migration into deeper soil. POEA, glyphosate, and AMPA were found on the bed sediment samples in urban and agricultural watersheds.

Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides.

The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general.

Increased plasma oleoylethanolamide and palmitoleoylethanolamide levels correlate with inflammatory changes in alcohol binge drinkers: the case of HMGB1 in women.

Alcohol binge drinking is a heavy pattern of alcohol consumption increasingly used by young people. In a previous study, we reported that young drinkers with a 2-year history of binge alcohol consumption had an overactivation of the innate immune system and peripheral inflammation when compared with controls. In the present study, we measured several biolipids that are fatty acid derivatives belonging to the acylethanolamide or 2-acylglycerol families in the plasma of the same subjects (n = 42; 20 men and 22 women). We found that during abstinence, alcohol binge drinkers had elevated plasma levels of oleoylethanolamide, palmitoleoylethanolamide, arachidonoylethanolamide, dihomo-γ-linolenoyl ethanolamide and linoleoyl ethanolamide, which positively correlated with changes in the mRNA expression of key inflammatory markers in peripheral blood mononuclear cells, such as toll-like receptors (TLR4), pro-inflammatory cytokines/chemokines interleukin-1 beta, interleukin-6 and monocyte chemoattractant protein-1, and cyclooxygenase-2. Additionally, plasma oleoylethanolamide positively correlated with plasma levels of high mobility group box-1, which is a danger-associated molecular pattern and an endogenous TLR4 agonist, specifically in female alcohol binge drinkers. No changes were observed in 2-acylglycerols in alcohol binge drinkers, although sex-related differences in these bioactive lipids as well as in palmitoleoylethanolamide and docosatetraenoylethanolamide levels were detected. These results extend the previous clinical findings observed in patients diagnosed with long-term alcohol use disorder to young users and suggest a prominent role for these lipids in the response to acute alcohol exposure.

The plasma lipidome in acute myeloid leukemia at diagnosis in relation to clinical disease features.

BACKGROUND: Early studies established that certain lipids were lower in acute myeloid leukemia (AML) cells than normal leukocytes. Because lipids are now known to play an important role in cell signaling and regulation of homeostasis, and are often perturbed in malignancies, we undertook a comprehensive lipidomic survey of plasma from AML patients at time of diagnosis and also healthy blood donors. METHODS: Plasma lipid profiles were measured using three mass spectrometry platforms in 20 AML patients and 20 healthy blood donors. Data were collected on total cholesterol and fatty acids, fatty acid amides, glycerolipids, phospholipids, sphingolipids, cholesterol esters, coenzyme Q10 and eicosanoids. RESULTS: We observed a depletion of plasma total fatty acids and cholesterol, but an increase in certain free fatty acids with the observed decline in sphingolipids, phosphocholines, triglycerides and cholesterol esters probably driven by enhanced fatty acid oxidation in AML cells. Arachidonic acid and precursors were elevated in AML, particularly in patients with high bone marrow (BM) or peripheral blasts and unfavorable prognostic risk. PGF2α was also elevated, in patients with low BM or peripheral blasts and with a favorable prognostic risk. A broad panoply of lipid classes is altered in AML plasma, pointing to disturbances of several lipid metabolic interconversions, in particular in relation to blast cell counts and prognostic risk. CONCLUSIONS: These data indicate potential roles played by lipids in AML heterogeneity and disease outcome. GENERAL SIGNIFICANCE: Enhanced catabolism of several lipid classes increases prognostic risk while plasma PGF2α may be a marker for reduced prognostic risk in AML.

The effect of glyphosate-based herbicide Roundup and its co-formulant, POEA, on the motoric activity of rat intestine - In vitro study.

The study was aimed at evaluating the effect of Roundup, polyoxyethylene tallow amine (POEA) and mixture of glyphosate and POEA in different levels on the motoric activity of jejunum strips. The incubation in the Roundup solutions caused a significant, mostly miorelaxant, reversible reaction of smooth muscle; only in the highest tested dose which is equivalent to the agricultural concentration (1% corresponding to 1.7g glyphosate/L) there was an irreversible disturbance of the spontaneous contractility and reactivity. The incubation in POEA solutions in the range of low doses (0.256; 1.28; 6.4mg/L) resulted in a biphasic muscle reaction (relaxation and contraction); whereas in the range of high doses, i.e. 32; 160 and 800mg/L (agricultural spray concentrations) induced only a miorelaxant, irreversible response. The results indicate very high toxicity of POEA which exceeds the toxicity of the commercial formulations. Besides, it is postulated that glyphosate and POEA may display antagonistic interaction towards the motoric activity of gastrointestinal tract.