The promotion of the atrazine degradation mechanism by humic acid in a soil microbial electrochemical system.

The enhancing effects of anodes on the degradation of the organochlorine pesticide atrazine (ATR) in soil within microbial electrochemical systems (MES) have been extensively researched. However, the impact and underlying mechanisms of soil microbial electrochemical systems (MES) on ATR degradation, particularly under conditions involving the addition of humic acids (HAs), remain elusive. In this investigation, a soil MES supplemented with humic acids (HAs) was established to assess the promotional effects and mechanisms of HAs on ATR degradation, utilizing EEM-PARAFAC and SEM analyses. Results revealed that the maximum power density of the MES in soil increased by 150%, and the degradation efficiency of ATR improved by over 50% following the addition of HAs. Furthermore, HAs were found to facilitate efficient ATR degradation in the far-anode region by mediating extracellular electron transfer. The components identified as critical in promoting ATR degradation were Like-Protein and Like-Humic acid substances. Analysis of the microbial community structure indicated that the addition of HAs favored the evolution of the soil MES microbial community and the enrichment of electroactive microorganisms. In the ATR degradation process, the swift accumulation of Hydrocarbyl ATR (HYA) was identified as the primary cause for the rapid degradation of ATR in electron-rich conditions. Essentially, HA facilitates the reduction of ATR to HYA through mediated bonded electron transfer, thereby markedly enhancing the efficiency of ATR degradation.

Occurrence and Ecological Risk of Alkylamine Triazines in Chinese Estuarine Sediments: An Emerging Class of Persistent, Mobile, and Toxic Substances.

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.

Swellable microneedle-coupled light-addressable photoelectrochemical sensor for in-situ tracking of multiple pesticides pollution in vivo.

In vivo monitoring of multiple pesticide contamination is of great significance for evaluating the health risks of different pesticides, agricultural production safety, and ecological and environmental assessment. Here, we report a hydrogel microneedle array coupled light-addressable photoelectrochemical sensor for tracking multiple pesticide uptake and elimination in living animals and plants, holding three prominent merits: i) enables in-situ detection of in vivo pesticides, avoiding cumbersome and complex sample transportation and handling processes; ii) allows repeated in vivo sampling of the same organism, improving tracking test controllability and accuracy; iii) avoids lethal sampling, providing a better understanding of the pesticides fate in living organisms. The coupled sensor is mechanically robust for withstanding more than 0.35 N per needle and highly swellable (800 %) for timely extraction of sufficient in vivo solution for analysis. For proof-of-concept, it achieves in-situ detection of atrazine, acetamiprid, and carbendazim efficiently and quantitatively in artificial agarose skin models, mouse skin interstitial fluids, and plant leaves with little inflammatory reaction. This simple, highly integrated, minimally invasive, and high-throughput in vivo monitoring method is ideal for future field environmental monitoring and plant and animal disease diagnosis.

Lipid-related ion suppression on the herbicide atrazine in earthworm samples in ToF-SIMS and matrix-assisted laser desorption ionization mass spectrometry imaging and the role of gas-phase basicity.

In mass spectrometry imaging (MSI), ion suppression can lead to a misinterpretation of results. Particularly phospholipids, most of which exhibit high gas-phase basicity (GB), are known to suppress the detection of metabolites and drugs. This study was initiated by the observation that the signal of an herbicide, i.e., atrazine, was suppressed in MSI investigations of earthworm tissue sections. Herbicide accumulation in earthworms was investigated by time-of-flight secondary ion mass spectrometry and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Additionally, earthworm tissue sections without accumulation of atrazine but with a homogeneous spray deposition of the herbicide were analyzed to highlight region-specific ion suppression. Furthermore, the relationship of signal intensity and GB in binary mixtures of lipids, amino acids, and atrazine was investigated in both MSI techniques. The GB of atrazine was determined experimentally through a linear plot of the obtained intensity ratios of the binary amino acid mixtures, as well as theoretically. The GBs values for atrazine of 896 and 906 kJ/mol in ToF-SIMS and 933 and 987 kJ/mol in MALDI-MSI were determined experimentally and that of 913 kJ/mol by quantum mechanical calculations. Compared with the GB of a major lipid component, phosphatidylcholine (GBPC = 1044.7 kJ/mol), atrazine's experimentally and computationally determined GBs in this work are significantly lower, making it prone to ion suppression in biological samples containing polar lipids.

[Effects of Pesticides Use on Pesticides Residues and Its Environmental Risk Assessment in Xingkai Lake（China）].

Xingkai Lake, located in Heilongjiang Province, is an important fishery and agricultural base and is seriously polluted by agricultural non-point sources. To clarify the residual status of many pesticides in the surface water of Xingkai Lake, 27 types of pesticides, herbicides, and their degradation products were analyzed in rice paddy, drainage, and surface water around Xingkai Lake (China) during the rice heading and maturity periods. The results showed that all 27 types of pesticides, herbicides, and their degradation products were detected during the rice heading period, and the total concentration ranged from 247.97 to 6 094.49 ng·L-1. Additionally, 25 species were detected during the rice maturity period, and the total concentration ranged from 485.36 to 796.23 ng·L-1. In comparison, more pesticides, herbicides, and derived degradation products were detected during the heading period, and their total concentration was higher as well. During the rice heading period, atrazine, simetryn, and paclobutrazol were the main detected pesticides, atrazine and isoprothiolane were the main pesticides detected during the maturity period. The distribution characteristics of pesticides and herbicides in the surface water around Xingkai Lake (China) was similar to that in drainage, so they were probably imported from the drainage and rice paddy. The average risk quotient (RQ) values of atrazine, simetryn, prometryn, butachlor, isoprothiolane, and oxadiazon were higher than 0.1 in drainage and Xingkai Lake (China), which showed a potential risk to aquatic organisms.

Prediction of atrazine degradation in soil based on XGBoost model.

We established the optimal model by using the automatic machine learning method to predict the degradation efficiency of herbicide atrazine in soil, which could be used to assess the residual risk of atrazine in soil. We collected 494 pairs of data from 49 published articles, and selected seven factors as input features, including soil pH, organic matter content, saturated hydraulic conductivity, soil moisture, initial concentration of atrazine, incubation time, and inoculation dose. Using the first-order reaction rate constant of atrazine in soil as the output feature, we established six models to predict the degradation efficiency of atrazine in soil, and conducted comprehensive analysis of model performance through linear regression and related evaluation indicators. The results showed that the XGBoost model had the best performance in predicting the first-order reaction rate constant (k). Based on the prediction model, the feature importance ranking of each factor was in an order of soil moisture > incubation time > pH > organic matter > initial concentration of atrazine > saturated hydraulic conductivity > inoculation dose. We used SHAP to explain the potential relationship between each feature and the degradation ability of atrazine in soil, as well as the relative contribution of each feature. Results of SHAP showed that time had a negative contribution and saturated hydraulic conductivity had a positive contribution. High values of soil moisture, initial concentration of atrazine, pH, inoculation dose and organic matter content were generally distributed on both sides of SHAP=0, indicating their complex contributions to the degradation of atrazine in soil. The XGBoost model method combined with the SHAP method had high accuracy in predicting the performance and interpretability of the k model. By using machine learning method to fully explore the value of historical experimental data and predict the degradation efficiency of atrazine using environmental parameters, it is of great significance to set the threshold for atrazine application, reduce the residual and diffusion risks of atrazine in soil, and ensure the safety of soil environment.

Behavioral and biochemical consequences after chronic exposition to the herbicide atrazine in tadpoles.

Atrazine (ATZ) is the third most sold herbicide in Brazil, occupying the seventh position between most widely used pesticides. Due to its easy outflow, low reactivity and solubility, moderate adsorption to organic matter and clay, and long soil persistence, residual herbicide can be identified after long periods following application, and its usage has been prohibited in diverse countries. Amphibians are important bioindicators to assess impact of pesticide like atrazine, due to having a partial aquatic life cycle. This study had as objective to assess the response of bullfrog (Lithobates catesbeianus) tadpoles when exposed to this herbicide. Animals were exposed for a total of 168h to following concentrations: negative control, 40 µg/L, 200 µg/L, 2000 µg/L, 20000 µg/L of ATZ. Analysis of swimming activity was performed, and biochemical profile was assessed by analysis of blood and plasma glucose levels, urea, creatinine, cholesterol, HDL, triglycerides, glutamic pyruvic transaminase (GPT), alkaline phosphatase (AP), calcium, total proteins, phenol, peroxidase and polyphenol oxidase activity. Results exhibited malnutrition, anemia, likely muscle mass loss, and hepatic damage, indicating that ATZ can lead to an increase in energy to maintain homeostasis for animal survival.

Degradation of Atrazine by an Anaerobic Microbial Consortium Enriched from Soil of an Herbicide-Manufacturing Plant.

Atrazine is an important herbicide that has been widely used for weed control in recent decades. However, with the extensive use of atrazine, its residue seriously pollutes the environment. Therefore, the microbial degradation and detoxification of atrazine have received extensive attention. To date, the aerobic degradation pathway of atrazine has been well studied; however, little is known about its anaerobic degradation in the environment. In this study, an anaerobic microbial consortium capable of efficiently degrading atrazine was enriched from soil collected from an herbicide-manufacturing plant. Six metabolites including hydroxyatrazine, deethylatrazine, N-isopropylammelide, deisopropylatrazine, cyanuric acid, and the novel metabolite 4-ethylamino-6-isopropylamino-1,3,5-triazine (EIPAT) were identified, and two putative anaerobic degradation pathways of atrazine were proposed: a hydrolytic dechlorination pathway is similar to that seen in aerobic degradation, and a novel pathway initiated by reductive dechlorination. During enrichment, Denitratisoma, Thiobacillus, Rhodocyclaceae_unclassified, Azospirillum, and Anaerolinea abundances significantly increased, dominating the enriched consortium, indicating that they may be involved in atrazine degradation. These findings provide valuable evidence for elucidating the anaerobic catabolism of atrazine and facilitating anaerobic remediation of residual atrazine pollution.

Nitrogen fertiliser-domesticated microbes change the persistence and metabolic profile of atrazine in soil.

Pesticides and fertilisers are frequently used and may co-exist on farmlands. The overfertilisation of soil may have a profound influence on pesticide residues, but the mechanism remains unclear. The effects of chemical fertilisers on the environmental behaviour of atrazine and their underlying mechanisms were investigated. The present outcomes indicated that the degradation of atrazine was inhibited and the half-life was prolonged 6.0 and 7.6 times by urea and compound fertilisers (NPK) at 1.0 mg/g (nitrogen content), respectively. This result, which was confirmed in both sterilised and transfected soils, was attributed to the inhibitory effect of nitrogen fertilisers on soil microorganisms. The abundance of soil bacteria was inhibited by nitrogen fertilisers, and five families of potential atrazine degraders (Micrococcaceae, Rhizobiaceae, Bryobacteraceae, Chitinophagaceae, and Sphingomonadaceae) were strongly and positively (R > 0.8, sig < 0.05) related to the decreased functional genes (atzA and trzN), which inhibited hydroxylation metabolism and ultimately increased the half-life of atrazine. In addition, nitrogen fertilisers decreased the sorption and vertical migration behaviour of atrazine in sandy loam might increase the in-situ residual and ecological risk. Our findings verified the weakened atrazine degradation with nitrogen fertilisers, providing new insights into the potential risks and mechanisms of atrazine in the context of overfertilisation.

Photo-thermal activation of persulfate for the efficient degradation of synthetic and real industrial wastewaters: System optimization and cost estimation.

The photo-thermal activation of persulfate (PS) was carried out to degrade various pollutants such as reactive blue-222 (RB-222) dye, sulfamethazine, and atrazine. Optimizing the operating parameters showed that using 0.90 g/L of PS at pH 7, temperature of 90 °C, initial dye concentration of 21.60 mg/L, and reaction time of 120 min could attain a removal efficiency of 99.30%. The degradation mechanism was explored indicating that hydroxyl and sulfate radicals were the prevailing reactive species. The degradation percentages of 10 mg/L of sulfamethazine and atrazine were 83.30% and 70.60%, respectively, whereas the mineralization ratio was 63.50% in the case of real textile wastewater under the optimal conditions at a reaction time of 120 min. The treatment cost per 1 m3 of real wastewater was appraised to be 1.13 $/m3 which assured the inexpensiveness of the proposed treatment system. This study presents an effective and low-cost treatment system that can be implemented on an industrial scale.

A mixture of mesotrione and atrazine harms adults and larvae of the predatory wasp Polistes satan.

Herbicides have been intensively used for weed control, raising concerns about their potentially adverse effects on non-target organisms. Research on the effects of these common agrochemicals on beneficial insects and the ecosystem services they provide (e.g., predation and pollination) is scarce. Therefore, we tested whether a commercial formulation comprising a mixture of mesotrione and atrazine was detrimental to adult females and larvae of the Neotropical predatory social wasp Polistes satan, which is an effective natural enemy of crop pests. Wasps were individually fed syrups contaminated with different concentrations of the herbicide above and below the maximum label rate (MLR = 12 mL/L). Survival was assessed. The locomotor activity, immune response, and midgut morphology of adults as well as the immune response of the larvae were also studied. Herbicide concentrations far above the MLR (12, 40, and 100 times) caused adult mortality, whereas lower concentrations (0.5, 1, and 6 times) did not. Herbicide exposure at 0.5 to 12 times the MLR increased adult activity. Adult exposure at 0.1 or 0.5 times the MLR did not affect melanotic encapsulation of foreign bodies but led to changes in the morphology of the midgut epithelium and peritrophic matrix. In larvae, the ingestion of herbicide at 0.1 or 0.2 times the MLR (corresponding to 9.6 and 19.2 ng of herbicide per individual) did not cause mortality but decreased their melanization-encapsulation response. Increased locomotor activity in herbicide-exposed adults can affect their foraging activity. The altered midgut morphology of adults coupled with the decreased immune response in larvae caused by herbicide exposure at realistic concentrations can increase the susceptibility of wasps to infections. Therefore, herbicides are toxic to predatory wasps.

A first survey for herbicide resistant weeds across major maize growing areas in the North Island of New Zealand.

Weeds are increasingly documented with evolved resistance to herbicides globally. Three species have been reported as resistant in maize crops in New Zealand: Chenopodium album to atrazine and dicamba, Persicaria maculosa to atrazine and Digitaria sanguinalis to nicosulfuron. Despite knowledge of these cases, the distribution of these resistant biotypes is unknown. This study aimed to determine the prevalence of known resistant weeds in major maize growing areas in New Zealand, and to pro-actively screen other species for resistance. Weed seeds of broadleaf and grass species were collected from 70 randomly selected maize growing farms in the North Island in 2021-2022. Seeds were grown and treated with herbicides at recommended field rates. Atrazine-resistant C. album were recorded in a third of surveyed farms and nicosulfuron-resistant D. sanguinalis in a sixth. Half of Waikato farms and a quarter of Bay of Plenty farms (no Hawkes Bay or Wellington farms) had atrazine-resistant C. album. Dicamba-resistant C. album were not detected, nor were atrazine-resistant P. maculosa. Nicosulfuron resistant D. sanguinalis was recorded in 19% of Waikato farms, 6% of Bay of Plenty farms and 9% of Hawkes Bay farms (no Wellington farms). Amaranthus spp., Fallopia convolvulus, Persicaria spp., Solanum spp., Echinochloa crus-galli, Panicum spp. and Setaria spp. were not resistant to any of the herbicides tested. Twenty-nine to 52% of maize farms in the North Island are estimated to have herbicide resistant weeds. Resistance is common in maize farms in Waikato and western Bay of Plenty. Resistance is rare in southern regions, with only one instance of nicosulfuron-resistant D. sanguinalis and no resistant C. album. Most annual weeds in maize are not resistant to herbicides; although atrazine resistant C. album is widespread, it is currently controlled with alternative herbicides. Resistant D. sanguinalis appears to be an emerging problem.

A combination of silymarin and garlic extract enhances thyroid hormone activation and body metabolism in orally intoxicated male rats with atrazine: Impact on hepatic iodothyronine deiodinase type 1.

Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.

Early and transitory hypoactivity and olfactory alterations after chronic atrazine exposure in female Sprague-Dawley rats.

Several studies have shown that chronic exposure to the herbicide atrazine (ATR) causes alterations in locomotor activity and markers of the dopaminergic systems of male rats. However, few studies have evaluated the sex-dependent effects of atrazine exposure. The aim of the present study was to evaluate whether chronic ATR exposure causes alterations in behavioral performance and dopaminergic systems of female rats. At weaning, two groups of rats were exposed to 1 or 10 mg ATR/kg body weight daily thorough the food, while the control group received food without ATR for 14 months. Spontaneous locomotor activity was evaluated monthly for 12 months, while anxiety, egocentric and spatial memory, motor coordination, and olfactory function tasks were evaluated between 13 and 14 months of ATR exposure. Tyrosine hydroxylase (TH) and monoamine content in brain tissue were assessed at the end of ATR treatment. Female rats treated with 1 or 10 mg ATR showed vertical hypoactivity compared to the control group only in the first month of ATR exposure. Impairments in olfactory functions were found due to ATR exposure. Nevertheless, no alterations in anxiety, spatial and egocentric memory, or motor coordination tasks were observed, while the levels of TH and dopamine and its metabolites in brain tissue were similar among groups. These results suggest that female rats could present greater sensitivity to the neurotoxic effects of ATR on spontaneous locomotor activity in the early stages of development. However, they are unaffected by chronic ATR exposure later in life compared to male rats. More studies are necessary to unravel the sex-related differences observed after chronic ATR exposure.

Deep degradation of atrazine in water using co-immobilized laccase-1-hydroxybenzotriazole-Pd as composite biocatalyst.

The efficient and green removal technology of refractory organics such as atrazine in water has been an important topic of research in water treatment. A novel membrane composite biocatalyst Lac-HBT-Pd/BC as prepared for the first time by co-immobilizing laccase, mediator 1-hydroxybenzotriazole (HBT) and metal Pd on functionalized bacterial cellulose (BC) to investigate the removal of atrazine and degradation of its intermediates under mild ambient conditions. It was found that atrazine could be completely degraded in 5 h by the catalysis of Lac-HBT-Pd/BC, and the removal rate of degradation intermediates from atrazine was about 85% after continuous catalysis, which achieved deep degradation of atrazine. The effect of electrochemical activity and radical stability of the membrane composite biocatalysts loaded with Pd was investigated. The possible degradation pathways were proposed by identifying and analyzing the deep degradation products of atrazine. The Lac-HBT-Pd/BC demonstrated deep degradation of atrazine and favorable reusability as well as considerable adaptability to various water qualities. This work provides an important reference for preparing new kinds of biocatalysts to degrade refractory organic pollutants in water.

MAPK/NF-κB signaling mediates atrazine-induced cardiorenal syndrome and antagonism of lycopene.

Atrazine (ATZ) is the most prevalent herbicide that has been widely used in agriculture to control broadleaf weeds and improve crop yield and quality. The heavy use of ATZ has caused serious environmental pollution and toxicity to human health. Lycopene (LYC), is a carotenoid that exhibits numerous health benefits, such as prevention of cardiovascular diseases and nephropathy. However, it remains unclear that whether ATZ causes cardiorenal injury or even cardiorenal syndrome (CRS) and the beneficial role of LYC on it. To test this hypothesis, mice were treated with LYC and/or ATZ for 21 days by oral gavage. This study demonstrated that ATZ exposure caused cardiorenal morphological alterations, and several inflammatory cell infiltrations mediated by activating NF-κB signaling pathways. Interestingly, dysregulation of MAPK signaling pathways and MAPK phosphorylation caused by ATZ have been implicated in cardiorenal diseases. ATZ exposure up-regulated cardiac and renal injury associated biomarkers levels that suggested the occurrence of CRS. However, these all changes were reverted, and the phenomenon of CAR was disappeared by LYC co-treatment. Based on our findings, we postulated a novel mechanism to elucidate pesticide-induced CRS and indicated that LYC can be a preventive and therapeutic agent for treating CRS by targeting MAPK/NF-κB signaling pathways.

l-Cysteine and barium titanate co-modified enteromorpha biochar as effective peroxymonosulfate activator for atrazine treatment.

In this study, pyrolysis and hydrothermal methods were used for Enteromorpha biochar that was co-modified with l-cysteine and barium titanate (LBCBa). It has great environmental tolerance and can remove 93.0 % of atrazine (ATZ, 10 mg·L-1) within 60 mins of ultrasonic treatment. The enhanced hydrophilicity, electron-donating capability, and piezoelectricity of LBCBa are considered to induce excellent performance. The apparent reaction rate of the LBCBa-2/PMS/ATZ system with ultrasonic was 2.87 times that without ultrasonic. The density functional theory points out that, introducing l-cysteine to carbon edges improves the adsorption of ATZ and peroxymonosulfate (PMS), making PMS easier to activate. This work offered unique insights for fabricating effective catalysts and demonstrated the combination of hydrophilic functional groups and piezoelectricity in improving catalytic performance and stability.

Atrazine Desorption Mechanism from an Hydrated Calcium Montmorillonite-A DFT Molecular Dynamics Study.

Atrazine is one of the most widely used herbicide molecules in the triazine family. Despite its interdiction in the European Union in 2004, atrazine and its main degradation products remain among the most frequently found molecules in freshwater reservoirs in many European Union countries. Our study aims in obtaining insight into the desorption process of atrazine from the main soil absorbent material: clay. Constrained Molecular Dynamics simulations within the Density Functional Theory framework allow us to obtain a free energy desorption profile of atrazine from a Ca2+-montmorillonite surface. The results are interpreted in terms of atrazine inclination to the clay surface and moreover, in terms of hydration states of the cations present in the clay interlayer as well as the hydration state of the atrazine. The desorption mechanism is driven by atrazine alkyl groups and their sizes because of dispersion stabilizing effects. The highest barrier corresponds to the loss of the isopropyl interaction with the surface.

Developmental regulation of cellular metabolism is required for intestinal elongation and rotation.

Malrotation of the intestine is a prevalent birth anomaly, the etiology of which remains poorly understood. Here, we show that late-stage exposure of Xenopus embryos to atrazine, a widely used herbicide that targets electron transport chain (ETC) reactions, elicits intestinal malrotation at high frequency. Interestingly, atrazine specifically inhibits the cellular morphogenetic events required for gut tube elongation, including cell rearrangement, differentiation and proliferation; insufficient gut lengthening consequently reorients the direction of intestine rotation. Transcriptome analyses of atrazine-exposed intestines reveal misexpression of genes associated with glycolysis and oxidative stress, and metabolomics shows that atrazine depletes key glycolytic and tricarboxylic acid cycle metabolites. Moreover, cellular bioenergetics assays indicate that atrazine blocks a crucial developmental transition from glycolytic ATP production toward oxidative phosphorylation. Atrazine-induced defects are phenocopied by rotenone, a known ETC Complex I inhibitor, accompanied by elevated reactive oxygen species, and rescued by antioxidant supplementation, suggesting that malrotation may be at least partly attributable to redox imbalance. These studies reveal roles for metabolism in gut morphogenesis and implicate defective gut tube elongation and/or metabolic perturbations in the etiology of intestinal malrotation.

An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

BACKGROUND: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. OBJECTIVE: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. METHODS: Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. RESULTS: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [rate ratios (RR)=1.24; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (RRQ4=1.20; 95% CI: 0.95, 1.52; p-trend=0.19), particularly among those <60 years old (RRQ4=3.04; 95% CI: 1.61, 5.75; p-trend<0.001; p-interaction=0.04). Among applicators <50 years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (RR=2.43; 95% CI: 1.10, 5.38; p-interaction=0.60). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (RRT3: 2.54; 95% CI: 0.97, 6.62; p-trend=0.31). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (RRT3=3.04; 95% CI: 1.45, 6.36; p-trend=0.07) and kidney (RRQ4=1.62; 95% CI: 1.15, 2.29; p-trend<0.005) cancers. DISCUSSION: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.