Polyethoxylated Tallow Amine Research Articles

Clinical toxicology of acute glyphosate self-poisoning: impact of plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amine surfactants on the toxicity

Introduction Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. Methods We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. Results Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69–0.97) and 0.76 (95% CI 0.59–0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). Discussion The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. Conclusions Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients.

Surfactant Coformulants in Glyphosate-Based Herbicides: Current Gaps, and Paths Forward in Human Biomonitoring.

Polyethoxylated tallow amine (POEA) surfactants in glyphosate formulations are understudied. They may constitute greater health risks than glyphosate itself. Lack of validated biomarkers of exposure and metabolism, as well as analytical methods for measuring POEA, limit the study of a formulation's toxicity and associated risk.

High-throughput analysis of polyethoxylated tallow amine homologs in citrus using a modified QuEChERS-HILIC-MS method.

A new method is described based on ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC) with electrospray mass spectrometry detection for comprehensive quantitative analysis of 66 polyethoxylated tallow amine (POE-tallowamine) homologs in citrus. Efficient separation, reduced band broadening, and high sensitivity were achieved by employing an acetonitrile-aqueous solution containing a 10 mM ammonium formate gradient on a hydrophilic interaction chromatography (HILIC) column with a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. The quantitative accuracy and precision of the method were improved by the use of matrix-matched calibration standards. At spiked levels of (50 + 250) μg/kg, (200 + 1000) μg/kg, and (500 + 2500) μg/kg POE-5 and POE-15 (1:5), the average recoveries of the POE-tallowamine homologs ranged from 71.9 to 112%, with RSDs < 16.6%. The limits of detection (LODs) and limits of quantification (LOQs) for POE-tallowamine homologs were 0.01-2.57 and 0.03-8.58 μg/kg, respectively. The method was successfully applied to determine POE-tallowamine in citrus samples from typical Chinese regions in 2021. POE-tallowamine was detected in all 54 samples, and the highest concentration (143 μg/kg) of POE-tallowamine was found in Jelly orange from Zhejiang Province, which might indicate a higher usage and demand of glyphosate herbicides in Zhejiang.

Rapid determination of polyethoxylated tallow amine surfactants in human plasma by LC-MSMS

The potential exposure to the widely used glyphosate-based herbicides, including attempted suicide by ingestion, is of world-wide concern. Whilst the major focus to date has been on managing exposure to the active ingredient glyphosate, it is now recognised that a common major ‘inert’ surfactant ingredient, polyethoxylated tallow amine (POEA) and related compounds, may be more toxic. However, the information on the toxicokinetics of POEA surfactants after exposure is limited, in part, due to the lack of suitable methods for their analysis in biological matrices. We therefore developed and validated a robust LC-MSMS method that allowed, for the first time, a rapid analysis of 11 POEA homologues in human plasma. Chromatographic separation was achieved on a Kinetex EVO C18 column under a 5 min gradient elution with mobile phase A containing water/acetonitrile/formic acid (95:5:0.1, v/v/v) and mobile phase B containing acetonitrile/water/formic acid (95:5:0.1, v/v/v). Amlodipine was chosen as the internal standard (IS) for this assay. Amlodipine-d4 would be an ideal alternative IS to expand the applicability of the established method especially in antihypertensive patients. Multiple reaction monitoring (MRM) methods were optimized for 11 POEA homologues and the IS. Sample pre-treatment was performed using simple protein precipitation with methanol at a ratio of 4:1, requiring only 20 μL plasma. The validated method showed good specificity, accuracy and precision with lower limits of quantification (LLOQ) ranging from 0.35 to 10.8 ng mL−1 for all selected POEA homologues. The method was then used to measure concentrations of the various POEA surfactants in more than 600 human plasma samples from 151 patients admitted to hospital with acute glyphosate intoxication. The highest concentrations ranged from 1.07 ng mL−1 for C18u(EO)4–362.70 ng mL−1 for C16s(EO)2. The analysis of POEA surfactants plasma concentrations as described here underpins the assessment of POEA internal exposure and the relationships between POEA related glyphosate toxicity and the extent of poisoning.

Glyphosate-Based Herbicide Causes Cellular Alterations to Gut Epithelium of the Neotropical Stingless Bee Melipona quadrifasciata quadrifasciata (Hymenoptera: Meliponini).

Glyphosate-based herbicides (GBH) are the best-selling pesticides in Brazil, with hundreds of thousands of tons sold per year. There is no study investigating morphological alterations caused by GBH on the epithelium of the gut in bees. Here, we aimed to demonstrate effects of chronic ingestion of GBH in the midgut digestive cells of the Brazilian stingless bee Melipona quadrifasciata quadrifasciata Lepeletier 1836. We kept forager workers of M. quadrifasciata in laboratory conditions and fed on food contaminated with three different concentrations of GBH for 10days, after which the midgut digestive cell structure and ultrastructure were analyzed. The presence of GBH in food did not affect food consumption, indicating that M. quadrifasciata bees do not reject food contaminated with GBH. As digestive cells of the midgut release apocrine secretion as a detoxication mechanism, we expected that the ingestion of food contaminated with GBH in the present study affect the height of midgut digestive cells. However, such reduction did not occur, probably because of the low-test concentrations. Although there were differences in digestive cell ultrastructure, ingestion of GBH impaired midgut digestive cell cohesion by disorganizing the smooth septate junctions between cells, which may probably be caused by the adjuvant "polyethoxylated tallow amine" present in the GBH. Previous studies demonstrated that GBH increase bees' sensibility to intestine infections, based on the present results we hypothesized that the loss of cell cohesion in the midgut epithelium favors pathogenic microbial infections and harms food absorption, increasing bees' mortality.

Challenges in direct determination of Glyphosate and aminomethylphosphonic acid in water by liquid chromatography-tandem mass spectrometry at modified reverse phase columns: Effect of matrix interferences in fresh and hard water systems.

This study validated two underivatized methods (M1 and M2) according to the Eurachem guidelines to analyze the herbicide Glyphosate and its major metabolite aminomethylphosphonic acid simultaneously by liquid chromatography-tandem mass spectrometry in both fresh and hard waters. Samples were analyzed directly after filtration through 0.22 μm syringe filters in M1, while samples were acidified with acetic acid before filtration in M2. Spike recoveries were greater than 80% for Glyphosate and aminomethylphosphonic acid in both methods. The limit of quantitation was 0.5 μg/L for M1, and 0.1 μg/L for M2 by using matrix-matched calibrations. The linear regression coefficient of both methods was greater than 0.995. The expanded uncertainty was found to be less than 25% for both. Moreover, M1 has an additional mass spectral confirmation ability, and the column and the mobile phase used in M2 can be used to analyze the inert surfactant used in Glyphosate formulations, Polyethoxylated tallow amine. The accuracy of the developed methods was assured by participating in a proficiency testing program against M2 and conducting the t-test for results generated by both M1 and M2. Both methods, therefore, can be used to determine Glyphosate and aminomethylphosphonic acid content concurrently in fresh and hard waters.

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning.

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning.

Cytotoxic effects of Roundup Classic and its components on NE-4C and MC3T3-E1 cell lines determined by biochemical and flow cytometric assays

Cytotoxic effects of the market leading broad-spectrum, synthetic herbicide product Roundup Classic, its active ingredient glyphosate (in a form of its isopropylamine (IPA) salt) and its formulating surfactant polyethoxylated tallowamine (POE-15) were determined on two murine cell lines, a neuroectodermal stem cell-like (NE-4C) and a high alkaline phosphatase activity osteoblastic cell line (MC3T3-E1). Cytotoxicity, genotoxicity, effects on cell viability and cell cycles were examined in five flow cytometry tests, the two former of which were compared by the enzymatic-assay and the alkaline single cell gel electrophoresis (Comet) assay. All of the tests indicated the NE-4C cells being more sensitive, than the MC3T3-E1 cell line to the treatments with the target compounds. Higher sensitivity differences were detected in the viability test by flow cytometry (7–9-fold), than by the MTT assay (1.5–3-fold); in the genotoxicity test by the Comet assay (3.5–403-fold), than by the DNA-damage test (9.3–158-fold); and in the apoptosis test by the Annexin V dead cell kit (1.1–12.7-fold), than by the Caspase 3/7 kit (1–6.5-fold). Cell cycle assays indicated high count of cells (~70%) in the G0/G1 phase for MC3T3-E1 cells, than in NE-4C cell (~40%) after 24 h. The order of the inhibitory potency of the target substances has unequivocally been POE-15 > Roundup Classic > > glyphosate IPA salt.

Eco-friendly surfactants in glyphosate formulation

Weeds affect various crops worldwide, causing low yields and, therefore, significant economic losses. These losses can be minimized by the use of herbicides such as glyphosate. However, the efficiency of glyphosate depends on the type of agrochemical formulations. The most widely used surfactant is polyethoxylated tallow amine. Nevertheless, the disadvantage of these compounds is that their toxicity is greater than that of glyphosate itself. Thus, this study aimed to develop an environmentally-friendly combination of surfactants that can increase the performance of glyphosate compared to other currently used formulations. Saponin (S) is environmentally friendly and has a unique ability to go through the waxy cuticle of the weed leaf. However, its interfacial properties are very poor. In contrast, the alkyl glucoside (AG) mixture has shown excellent interfacial properties, being an environmentally safe surfactant, but cannot pass through the cuticle. In the present study, we mixed both surfactants. Two formulations were made with 20% (F1) and 2% (F2) of S with 4% AG. To verify the usefulness of our formulations, they were compared against a commercial product. The results showed that the commercial product had better CMC 0.3±0.1% and pC20 1.155±0.099 than our formulations F1 and F2. Formulations F1 and F2 showed better gCMC than the commercial product 36.5±4.1 mN/m and 30.9±1.4 mN/m, respectively. Field tests showed that F2 was more effective than the commercial product in eliminating weeds at the end of the test at 30 days. Our results allowed confirming that the use of saponin improves the efficiency of glyphosate. The work showed that structures similar to cyclopentaneperhydrophenanthrene are very effective for introducing drugs into plants through the leaves. This is an advance in general and in particular for the increase of the yield in certain crops.

Toxicity of glyphosate-based isopropylamine salt and polyethoxylated tallow amine formulations on juvenile Clarias gariepinus

The formulation of glyphosate composed of Isopropylamine salt and Polyethoxylated tallow Amine (Clearweed) is widely used as herbicide to control weeds both in the terrestrial and aquatic environments. A static bioassay was conducted to examine toxicity of this formulation on juvenile African catfish (Clarias gariepinus). Catfish juvenile (mean weight 27.97±0.03g) were exposed to glyphosate at concentrations of 0.00mg/l (control), 5.00, 7.50, 10.00, 12.50 and 15.00mg/l. Each concentration was treated in triplicate and the exposure period lasted for 96 hrs. Mortality rates and physico-chemical parameters of water were monitored. Results revealed that fish mortality increased with increasing concentration of glyphosate and time of exposure. The median lethal concentration (96-hr LC50) value was 8.88mg/l with the upper and lower limits of 9.10mg/l and 7.75mg/l respectively. Behavioural changes observed the treated fish included: erratic swimming, jerky movement, increased opercula and tail movements, gulping of air, lost of balance and consciousness, cessation of opercula and tail movement signifying eventual death. Water quality parameters increased significantly (p&lt;0.05) with extract concentration except dissolve oxygen levels which reduced (p&lt;0.05). However, all values reported were within the permissible limits of the Federal Ministry of Environment (FMEnv) for water samples. The results of this study indicated that glyphosate formulation has toxic effects on catfish. Thus, the herbicide should be cautiously used to avoid ecotoxicological hazards particularly on 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.

Banning of herbicides and the impact on agriculture: the case of glyphosate in Sri Lanka

AbstractGlyphosate, a widely used preplant herbicide in annual and perennial crops, was introduced to Sri Lanka in 1977. Its use has expanded since 2008 with the phase-out and ban in 2014 of paraquat. In December 2014, glyphosate use in Sri Lanka was regionally restricted. Crop protection and production in the country was severely affected in 2016 and 2017 due to the irrational decisions of the government of Sri Lanka (GoSL). Increased crop production costs due to the absence of effective and economically viable weed control techniques, low crop yields, loss of foreign exchange, and enhanced use of smuggled glyphosate products are the consequences of the glyphosate ban. The ban was imposed without a scientific basis because of sociopolitical pressure. A series of dialogues with the GoSL helped rescind the ban in 2018 for a period of 36 mo, but its use is limited to tea [Camellia sinensis (L.) Kuntz.] and rubber [Hevia brasiliensis (Willd. ex A. Juss.) Müll. Arg.]. In August 2019, the Cabinet of Ministers of the GoSL also decided to allow use of glyphosate to devitalize propagules in the floriculture industry (export oriented) and destroy coconut (Cocos nucifera L.) trees infected by Weligama coconut leaf wilt disease and sugarcane (Saccharum officinarum L.) infected by white leaf disease. However, glyphosate products with the co-formulant polyethoxylated tallow amine are still not permitted in Sri Lanka.

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.

Adverse Metabolic Outcomes in Soil Pseudomonas Species Exposed to Polyethoxylated Tallow Amine and Glyphosate

Polyethoxylated tallow amine (POEA) is a common surfactant used in glyphosate-based herbicide formulations to enhance the bioavailability of the active herbicide ingredient. Toxic effects of POEA e...

Increased severity associated with tallowamine in acute glyphosate poisoning

Context: During the re-approval process of glyphosate in Europe, it was mentioned that glyphosate-based products (GBF) were more toxic than glyphosate alone. This phenomenon was attributed to the surfactants and among them, polyethoxylated tallowamine (POEA) has been suspected to significantly contribute to the toxicity of glyphosate products. In animal data acute oral toxicity of POEA has been suggested to be greater than glyphosate toxicity in animal studies. There are no data, however, comparing the clinical signs and severity of acute human poisoning with tallowamine-containing GBF (TA) and non-tallowamine-containing GBF (NTA). The aim of this study was to compare the severity of oral poisoning between TA and NTA cases, reported to the French Poison Control Centres (PCC) over 7 years.Methods: This is a retrospective study of cases of oral exposure to GBF reported to French PCCs between January 1st, 2008 and December 12th, 2014. The formulation of every GBF was reviewed using the PCC national database of products and compositions, to identify cases involving TA, NTA, or GBF with unknown co-formulants.Results: Between 2008 and 2014, 1362 cases of GBF ingestion were registered in the PCC national database of poisoning cases. Among them, 429 were symptomatic acute cases of ingestion of GBF. There were 235 exposures to TA, 105 to NTA, and 89 to unknown GBF. There were more severe cases in the TA group than in the NTA group (p = 0.037).Discussion: The present study shows that POEA rather than other co-formulants leads to more severe symptoms in those patients ingesting GBF. The acute toxicity of POEA might be explained by its irritating properties; in experimental studies, it caused skin irritation and severe eye and mucous membranes irritation.Conclusion: In this study, severe respiratory symptoms were also more frequently reported in the TA group. The surfactant properties of POEA are likely to cause aspiration pneumonitis which is a plausible explanation for the respiratory failure complicating severe GBF poisoning cases.

A natural adjuvant shows the ability to improve the effectiveness of glyphosate application.

Glyphosate is a common herbicide used worldwide, but its adjuvant has not been studied much. A new adjuvant A-178®, based on the coconut shell extracts, has been developed for glyphosate (glyphosate isopropylamine salt: GP). The potency of the new adjuvant was compared with traditional adjuvant polyethoxylated tallow amine (POEA). Field study has shown that A-178® can improve the herbicidal effect of GP formulation, and, as compared with 41% GP mixed with 7% POEA (GPP), 41% GP mixed with 7% A-178® (recommended dose, GPA) is more effective for weed control. GPA improved herbicidal activity against GP alone by 79.27% and against GPP by 27.38% at 500 g a.i./ha. A-178® decreased the surface tension, increased the spreading area of GP, and improved the uptake of GP in cockspur (Echinochloa crus-galli L.). Our results indicated that the new adjuvant shows better ability to improve glyphosate efficacy than does POEA.

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.

Impact of the glyphosate-based commercial herbicide, its components and its metabolite AMPA on non-target aquatic organisms

Glyphosate (GLY) is the active ingredient of several herbicide formulations widely used to control weeds in agricultural and non-agricultural areas. Due to the intensive use of GLY-based herbicides and their direct application on soils, some of their components, including the active ingredient, may reach the aquatic environment through direct run-off and leaching. The present study assessed the acute toxicity and genotoxicity of the GLY-based formulation Atanor 48 (ATN) and its major constituents GLY, surfactant polyethoxylated tallow amine (POEA), as well as the main metabolite of GLY aminomethylphosphonic acid (AMPA) on non-target aquatic organisms. The toxic effects of these chemicals were evaluated in the fish embryo acute toxicity test with zebrafish (Danio rerio), while genotoxic effects were investigated in the comet assays with cells from zebrafish larvae and rainbow trout gonad-2 (RTG-2). GLY and AMPA caused no acute toxic effect, while ATN and POEA induced significant lethal effects in zebrafish (LC50-96 h 76.50 mg/L and 5.49 mg/L, respectively). All compounds were genotoxic in comet experiments with zebrafish larvae (LOEC 1.7 mg/L for GLY, ATN, AMPA and 0.4 mg/L for POEA). Unlike in vivo, only POEA induced DNA damage in RTG-2 cells (LOEC 1.6 mg/L), suggesting that it is a direct acting genotoxic agent. In summary, these data indicate that the lethal effects on zebrafish early-life stages can be ranked in the following order from most to least toxic: surfactant POEA > formulation ATN > active ingredient GLY ≈ metabolite AMPA. Genotoxic effects were observed in both RTG-2 cells (only POEA) and zebrafish (all test compounds) with the lowest tested concentrations. Therefore, it is important to evaluate different toxicological endpoints as well as use different non-target organisms to predict the hazards of GLY-based formulations and their components and breakdown product to aquatic biota.

An integrative omics approach to unravel toxicity mechanisms of environmental chemicals: effects of a formulated herbicide

The use of integrative molecular approaches can aid in a comprehensive understanding of the effects of toxicants at different levels of biological organization, also supporting risk assessment. The present study aims to unravel the toxicity mechanisms of a widely used herbicide to the arthropod Folsomia candida exposed in a natural soil, by linking effects on reproduction, proteomics and genome-wide gene expression. The EC50 effects on reproduction over 4 weeks was 4.63 mg glyphosate/kg of soil. The formulation included a polyethoxylated tallowamine as an adjuvant, which at 50% effect on reproduction had an estimated concentration of 0.87–1.49 mg/kg of soil. No effects were observed on survival and reproduction when using the isolated active substance, pointing the toxicity of the formulated product to the co-formulant instead of the active ingredient, glyphosate. RNA sequencing and shotgun proteomics were applied to assess differential transcript and protein expressions between exposed and control organisms in time, respectively. Specific functional categories at protein and transcriptome levels were concordant with each other, despite overall limited correlations between datasets. The exposure to this formulation affected normal cellular respiration and lipid metabolism, inducing oxidative stress and leading to impairment in biological life cycle mechanisms such as molting and reproduction.