Simultaneous determination of diquat, paraquat, glufosinate, and glyphosate in plasma by liquid chromatography/tandem mass spectrometry: from method development to clinical application.

Diquat (DQ), paraquat (PQ), glufosinate (GLU), and glyphosate (GLYP) are commonly used herbicides that have been confirmed to be toxic to humans. Rapid and accurate measurements of these toxicants in clinical practice are beneficial for the correct diagnosis and timely treatment of herbicide-poisoned patients. The present study aimed to establish an efficient, convenient, and reliable method to achieve the simultaneous quantification of DQ, PQ, GLU, and GLYP in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without using derivatization or ion-pairing reagents. DQ, PQ, GLU, and GLYP were extracted by the rapid protein precipitation and liquid-liquid extraction method and then separated and detected by LC-MS/MS. Subsequently, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, extraction recovery, matrix effect, dilution integrity, and stability were evaluated to validate the method based on the FDA criteria. Finally, the validated method was applied to real plasma samples collected from 166 Chinese patients with herbicide poisoning. The results showed satisfactory linearity with low LOD (1 ng/mL for DQ and PQ, 5 ng/mL for GLU, and 10 ng/mL for GLYP, respectively) and low LOQ (5 ng/mL for DQ and PQ, 25 ng/mL for GLU and GLYP, respectively). In addition, the precision, accuracy, extraction recovery, and stability of the method were acceptable. The matrix effect was not observed in the analyzed samples. Moreover, the developed method was successfully applied to determine the target compounds in real plasma samples. These data provided reliable evidence for the application of this LC-MS/MS method for clinical poisoning detection.

Integration of paraquat pharmacokinetic data across species using PBPK modelling.

Paraquat dichloride (PQ) is a non-selective herbicide which has been the subject of numerous toxicology studies over more than 50 years. This paper describes the development of a physiologically-based pharmacokinetic (PBPK) model of PQ kinetics for the rat, mouse and dog, firstly to aid the interpretation of studies in which no kinetic measurements were made, and secondly to enable the future extension of the model to humans. Existing pharmacokinetic data were used to develop a model for the rat and mouse. Simulations with this preliminary model were then used to identify key data gaps and to design a new blood binding study to reduce uncertainty in critical aspects of the model. The new data provided evidence to support the model structure, and its predictive performance was then assessed against dog and rat datasets not used in model development. The PQ-specific model parameters are the same for all three species, with only the physiological parameters varying between species. This consistency across species provides a strong basis for extrapolation to other species, as demonstrated here for the dog. The model enables a wide range of PQ data to be linked together to provide a broad understanding of PQ pharmacokinetics in rodents and the dog, showing that the key aspects of PQ kinetics in these species are understood and adequately encapsulated within the model.

Paraquat pharmacokinetics in primates and extrapolation to humans.

By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.

Simultaneous determination of paraquat and diquat in human plasma by HPLC-DAD: Its application in acute poisoning patients induced by these two herbicides.

BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.

Metabolitic profiling of amino acids in paraquat-induced acute kidney injury.

BACKGROUND: The herbicide paraquat (1, 1'-dimethyl-4, 4'-bipyridylium dichloride; PQ) is a poison well-known to cause delayed mortality due to acute kidney injuries (AKI). This study examines the changes in serum amino acids (AAs) metabolite profiles as surrogate markers of renal cell metabolism and function after paraquat poisoning. METHODS: To identify the metabolic profiling of free serum AAs and its metabolites, serum from 40 paraquat-poisoned patients with or without AKI is collected. LC-MS/GC-MS is performed to analyze AA molecules. A Cox proportional hazard model was used to assess for incidence of AKI. Receiver operating characteristic (ROC) curve is applied to evaluate AKI occurrence and prognosis. RESULTS: A total of 102 serum AAs and its metabolites were identified. Compared with non-AKI patients, 37 varied significantly in AKI patients. The univariate Cox proportional hazard model analysis revealed that the estimated PQ amount, plasma PQ concentration, urine PQ concentration, APACHE, SOFA scores and 16 amino acids correlated with the incidence of AKI. Further analyses revealed that 3-methylglutarylcarnitine, 1-methylimidazoleacetate, and urea showed higher cumulative hazard ratios for the occurrence of AKI during follow-up (P < 0.05). The area under the curve (AUC) of 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were 0.917, 0.857, 0.872, respectively. CONCLUSION: 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.

Serial measurement of glyphosate blood concentration in a glyphosate potassium herbicide-intoxicated patient: A case report.

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.

Comparative Pharmacokinetics of High and Low Doses of the Herbicide Propanil in Mice.

We have documented that the herbicide propanil is immunotoxic in mice, and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound, that require concentrations higher than environmental levels. The aim of this study was to compare tissue PK after exposure to propanil concentrations more relevant to levels of exposure to agricultural workers and the general population to concentrations previously reported for laboratory studies. To this end, we conducted a study to measure propanil distribution in three immune organs, using ultrasensitive accelerator mass spectrometry (AMS). We used two doses: the lower dose modeled levels expected in the environment or long-term occupational exposure to low doses, while the higher dose was to model the effects of an accidental exposure. Our results showed that the distribution and PK profiles from these two different concentrations was markedly different. The profile of the high dose (concentration) exposure was indicative of saturation of the detoxifying capability of the animal. In contrast, at the lower environmentally relevant concentration, in vivo concentrations of propanil in spleen, liver, and blood dropped to a very low level by 720 min. In conclusion, these studies highlight the differences in PK of propanil at these two doses, which suggests that the toxicity of this chemical should be re-investigated to obtain better data on toxic effects at doses relevant for humans.

[Determination of paraquat in serum by ultra performance liquid chromatography tandem mass spectrometry and toxicokinetics of paraquat in rat].

OBJECTIVE: To establish a simple and rapid ultra-performance liquid chromatography tandem mass spectrometry( UPLC-MS/MS) method for the determination of paraquat in serum, and to apply to the toxicokinetics of paraquat in rats. METHODS: The samples separated on ACQUITY UPLC BEH HILIC column( 2. 1 mm × 50 mm, 1. 7 µm)with acetonitrile-50 mmol/L ammonium formate( 0. 4% formic acid) as mobile phase. The analytes were analyzed using ESI operating in the positive multiple reaction monitoring( MRM) mode. The method was used in toxicokinetic study in poisoned rat. Toxicokinetic parameters were calculated by WinNonlin 7. 0 statistical software. RESULTS: Paraquat was linear in the range of 0. 3-1000. 0 µg/L, the recovery rate was 89. 0%-107. 7%, and the relative standard deviation( RSD) 1. 9%-13. 8%( n = 6). Toxicokinetic parameterswere as follows: C_(max), T_(max)and T_(1/2) were( 46. 50 ± 5. 11) mg/L, 0. 167 h, ( 63. 2 ±16. 2) h, respectively. CONCLUSION: This method is highly sensitive, high accuracy and is suitable for the analysis of paraquat in the toxicokinetic study in rats.

Analysis of Common Herbicides in Blood by UPLC-HRMS.

OBJECTIVES: To develop a method to screen and quantify 10 common herbicides （paraquat, diquat, glyphosate, glufosinate, cyanazine, atrazine, metazachlor, acetochlor, chlorsulfuron, and metsulfuron） in blood. METHODS: With acetonitrile-water solution [V（acetonitrile）∶V（water）=3∶1] as protein precipitant, 10 common herbicides in blood were detected using ultra-high performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. RESULTS: All the 10 herbicides had good linearity in their linear range （coefficient of determination R2≥0.993）, with the recovery rates 67.4%-111.9%, the relative standard deviations 1.5%-10.8%, the accuracies 85.1%-106.1%, intra-day precisions 2.7%-13.5%, and inter-day precisions 3.3%-13.3%. CONCLUSIONS: This method is easy to operate with high recovery rates. It enables rapid and accurate qualitative screening and quantitative analysis of various herbicides in blood simultaneously.

[Experimental study scavenging effect of paraquat by hemoperfusion].

Objective: To determine the scavenging effect and the change of metabolism of paraquat (PQ) using hemoperfusion (HP) once and twice within 12 hours after intoxication and explore the better scheme of HP. Methods: 18 beagles were randomly divided into 3 groups. Single HP group, Double HP group and Control group. Peripheral veins blood was collected at different times within 48 hours after exposure in each group. Toxin concentration was measured, analyzed and compared among 3 groups. Results: 6 hours after exposure, Single HP group and Double HP group has finished the first HP treatment, and the concentration of PQ was lower than that of the control group, the difference was statistically significant (P<0.05) . 10 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . 12 hours after exposure, Double HP group has finished the second HP treatment, the concentration of PQ was significantly lower than that of Single HP group and Control group (P<0.05) . 24 hours and 48 hours after exposure, there was no statistical difference of toxin concentration among 3 groups (P>0.05) . Statistical difference were not observed in toxicokinetical parameters among 3 groups (P>0.05) . Conclusion: HP treatment once and twice within 12 hours after intoxication could effectively reduce the toxin concentration in the peripheral veins blood after HP for about 4 hours, then the toxin concentration would return to the same level as Control group quickly. It was suggested that at the beginning of poisoning, HP treatment once or twice could not significantly change the metabolism of paraquat.

Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.

Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.

Metabolism and physiologically based pharmacokinetic modeling of flumioxazin in pregnant animals.

A physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of flumioxazin, in the blood and fetus of pregnant humans during a theoretical accidental intake (1000mg/kg). The data on flumioxazin concentration in pregnant rats (30mg/kg po) was used to develop the PBPK model in pregnant rats using physiological parameters and chemical specific parameters. The rat PBPK model developed was extrapolated to a human model. Liver microsomes of female rats and a mixed gender of humans were used for the in vitro metabolism study. To determine the % of flumioxazin absorbed after administration at a dose of 1000mg/kg assuming maximum accidental intake, the biliary excretion study of [phenyl-U-(14)C]flumioxazin was conducted in bile duct-cannulated female rats (Crl:CD (SD)) to collect and analyze the bile, urine, feces, gastrointestinal tract, and residual carcass. The % of flumioxazin absorbed at a dose of 1000mg/kg in rats was low (12.3%) by summing up (14)C of the urine, bile, and residual carcass. The pregnant human model that was developed demonstrated that the maximum flumioxazin concentration in the blood and fetus of a pregnant human at a dose of 1000mg/kg po was 0.86µg/mL and 0.68µg/mL, respectively, which is much lower than Km (202.4µg/mL). Because the metabolism was not saturated and the absorption rate was low at a dose of 1000mg/kg, the calculated flumioxazin concentration in pregnant humans was thought to be relatively low, considering the flumioxazin concentration in pregnant rats at a dose of 30mg/kg. For the safety assessment of flumioxazin, these results would be useful for further in vitro toxicology experiments.

Serum dioxin levels in Vietnamese men more than 40 years after herbicide spraying.

Recent studies have found elevated dioxin levels inside some U.S. military former air bases in Vietnam, known as hotspots. Many studies of Agent Orange have been done in U.S. veterans; however, there is little known about Vietnamese men. In 2010, we collected blood samples from 97 men in a hotspot and 85 men in an unsprayed area in Northern Vietnam. Serum concentrations of not only TCDD but also other dioxins (PCDDs), furans (PCDFs), and nonortho polychlorinated biphenyls (PCBs) were significantly higher in the hotspot than in the unsprayed area. In the hotspot, three subareas were demarcated, based on their proximity to the air base. The total toxic equivalents (TEQ) of PCDDs/PCDFs+PCBs was 41.7 pg/g lipid in the area closest to the air base, while it was around 29 pg/g lipid in the other two subareas. In the unsprayed area, the dioxin levels were no different between men who went to the South during the Vietnam War and those who remained in the North, with TEQs PCDDs/PCDFs+PCBs of around 13.6 pg/g lipid. Our findings suggested that people living close to the former U.S. air bases might have been exposed to both Agent Orange and other sources of dioxin-like compounds.

Prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning: a retrospective study.

Objectives: Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. Methods: This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Results: Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Conclusion: Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.

A highly efficient and selective rapid detection method applied to the detection of amide herbicides in fish serum.

Misuse of amide herbicides in the fisheries environment can pose unpredictable harm to aquatic products and ultimately human health. Thus, the development of a real-time, rapid on-site detection method is crucial. This study proposes for the first time, a paper-based visual detection method for amide herbicides in fish serum, by coating the molecularly imprinted polymer layer onto quantum dots, prepared fluorescent sensing materials (QDs@MIPs) for the detection of amide herbicides in aquatic products. These materials specifically cause fluorescence quenching in the presence of amide herbicides resulting in a color change. For practical application, this research designed a rapid test strip based on QDs@MIPs, meanwhile, incorporate a smartphone or a fluorescence spectrophotometer for qualitative and quantitative measurements, the limit of detection ranges of 0.061-0.500 µM. The method can be used for on-site evaluation of aquatic products, providing new technology for monitoring the safety of aquatic products.

Diagnostic and prognostic value of diquat plasma concentration and complete blood count in patients with acute diquat poisoning based on random forest algorithms.

Currently, the incidence of diquat (DQ) poisoning is increasing, and quickly predicting the prognosis of poisoned patients is crucial for clinical treatment. In this study, a total of 84 DQ poisoning patients were included, with 38 surviving and 46 deceased. The plasma DQ concentration of DQ poisoned patients, determined by liquid chromatography-mass spectrometry (LC-MS) were collected and analyzed with their complete blood count (CBC) indicators. Based on DQ concentration and CBC dataset, the random forest of diagnostic and prognostic models were established. The results showed that the initial DQ plasma concentration was highly correlated with patient prognosis. There was data redundancy in the CBC dataset, continuous measurement of CBC tests could improve the model's predictive accuracy. After feature selection, the predictive accuracy of the CBC dataset significantly increased to 0.81 ± 0.17, with the most important features being white blood cells and neutrophils. The constructed CBC random forest prediction model achieved a high predictive accuracy of 0.95 ± 0.06 when diagnosing DQ poisoning. In conclusion, both DQ concentration and CBC dataset can be used to predict the prognosis of DQ treatment. In the absence of DQ concentration, the random forest model using CBC data can effectively diagnose DQ poisoning and patient's prognosis.

Rapid determination of glyphosate and glufosinate in human blood by probe electrospray ionization tandem mass spectrometry.

In forensic science, glyphosate (GLYP) and glufosinate (GLUF), a class of non-selective broad-spectrum herbicides, have been frequently encountered in many fatal poisoning and suicide cases due to their widespread availability. Therefore, it is essential to develop an effective method for detecting these compounds. Some conventional methods, such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), have been reported to detect these compounds. However, these methods are not ideal for their time-consuming and non-sensitive feature. Herein, probe electrospray ionization (PESI) tandem mass spectrometry (MS/MS), a fast and sensitive technique, was applied for the determination of GLYP and GLUF in human blood, which can obtain analytical results within 0.5 min without derivatization and chromatographic separation. After protein precipitation of blood samples, the supernatant was mixed with isopropanol and ultra-pure water (1:1 v/v). Then, 8 µL of the mixture was introduced into the plastic sample plate for PESI-MS/MS analysis. The limits of detection (LODs) of the method were 0.50 µg/mL and 0.25 µg/mL for two analytes, and the limits of quantitation (LOQs) were both 1.00 µg/mL, which are higher than the concentration of reported poisoning and fatal cases. In the linear range of 1-500 µg/mL, the regression coefficients (r2) for GLYP and GLUF were over 0.99. The matrix effects ranged from 94.8 % to 119.5 %, and the biases were below 4.3 %. The recoveries ranged between 84.8 % and 107.4 %, and the biases were below 7.6 %. Meanwhile, the method was effectively utilized to detect and quantify the blood, urine, and other samples. Consequently, the results suggest that PESI-MS/MS is a straightforward, fast, and sensitive method for detecting GLUF and GLYP in forensics. In the future, PESI-MS/MS will become an indispensable technique for polar substances in grassroots units of public security where rapid detection is essential.

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.

[Predictive value of 3 methods in severity evaluation and prognosis of acute paraquat poisoning].

OBJECTIVE: To evaluate the predictive value of 3 methods, namely plasma paraquat concentration, severity index of paraquat poisoning (SIPP), and acute physiology and chronic health evaluation (APACHE II) in severity evaluation and prognosis of acute paraquat poisoning. METHODS: A total of 73 acute paraquat poisoning patients with oral administration were collected. Paraquat concentration in the plasma and other parameters on admission for SIPP and APACHE II were taken from medical records. According to the clinical outcome in the hospital or 7 days after the discharge, discrimination and calibration test were performed to evaluate the prognosis of the 3 methods. RESULTS: Discrimination of the 3 methods was greater than 0.8, and the area under the receiver operator curve for SIPP (0.938) was greater than paraquat concentration in the plasma (0.857) and APACHE II (0.801) with statistical significance (z=2.429, 2.021; P=0.015, 0.043). Difference in plasma paraquat concentration (0.857) and APACHE II (0.801) had no statistical significance (z=0.755, P=0.450). Hosmer-Lemeshow good fit test suggested better calibration value with statistical significance for the 3 methods (P>0.05). CONCLUSION: The 3 methods are valid in the severity evaluation and prognosis of acute paraquat poisoning. SIPP is the most preferred method, followed by paraquat concentration on admission. When there is no facility to measure paraqut concentration, APACHE II can be used as a reference for the death risk in acute paraquat poisoning.