[Analysis of 5 patients with acute glyphosate poisoning clinical characteristics and metabolic concentration].

Objective: To analyze the correlation between changes in the concentration of glyphosate (GLY) and its metabolites (AMPA) in patients with acute glyphosate poisoning and clinical symptoms, and to provide reference for the study of glyphosate toxicity. Methods: Urine samples from 5 patients with oral glyphosate poisoning admitted to the Emergency Department of Yangzhou Third Class A General Hospital from February to July 2021 were collected. Urine concentrations of GLY and AMPA were measured using derivatization gas chromatography-mass spectrometry, and analyzed based on the patient's clinical manifestations and treatment process. Results: The main symptoms of the patient after poisoning were acute gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, etc. The concentration of GLY in the patient's urine reached its maximum on the first day and gradually decreased over time. On the day of discharge, the final concentration of GLY was 10% lower than the initial concentration. At discharge, the clearance rates of GLY in cases 1, 2, 3, and 4 were 96.97%, 95.91%, 96.87% and 92.87%, respectively. Conclusion: The glyphosate has a shorter maintenance time after entering the human body; There is no correlation between the concentration of glyphosate and its metabolites admitted to the hospital, the dose of poisoning, and clinical symptoms in poisoned patients.

[Investigation on health status of workers exposed to glyphosate].

Objective: To analyze the concentrations of glyphosate and its metabolites in occupational exposed workers and their possible effects on human health, so as to provide a reference for improving the safe use of glyphosate and toxicity research. Methods: From April to December 2020, 247 workers directly exposed to glyphosate in 5 enterprises were selected as the contact group, and 237 workers who were not exposed to glyphosate and other pesticides in the same enterprise were selected as the control group. Questionnaire survey and occupational health examination were conducted on objects, and the concentrations of glyphosate and its metabolites in the air of workplaces and biological samples were detected. The correlation between the concentrations and the difference of health examination between the two groups were analyzed. Results: The urine glyphosate concentration (0.022-47.668 mg/L), the rate of exceeding the standard (60.32%, 149/247) and the urine aminomethyl phosphonic acid concentration (<0.010-1.624 mg/L) in the contact group were higher than those in the control group [urine glyphosate concentration (<0.020-4.482 mg/L), the rate of exceeding the standard (2.53%, 6/237) and the urine aminomethyl phosphonic acid concentration (<0.010-0.524 mg/L) ], respectively (P<0.001). The exceeding standard rate of glyphosate concentration in the workplace was 33.67% (33/98). The concentration of glyphosate in the workplace was positively correlated with the concentrations of glyphosate and aminomethylphosphonic acid in urine (r(s)=0.804, 0.238, P<0.001), and the concentration of glyphosate in urine was positively correlated with the concentration of aminomethylphosphonic acid in urine (r(s)=0.549, P<0.001). The alanine aminotransferase (ALT), white cell ratio, creatinine, uric acid, the abnormal rates of ALT and total protein (TP) in the contact group were higher than those in the control group, and TP was lower than that in the control group, the differences were statistically different (P<0.05). The abnormal rates of overall liver function, overall renal function, blood routine test, urine routine test, electrocardiogram, liver B ultrasound and blood lipid in the contact group were significantly higher than those in the control group (P<0.05) . Conclusion: The concentration of glyphosate in the workplace is related to the concentrations of glyphosate and aminomethyl phosphonic acid in the urine of workers, and exposure to glyphosate may have some harmful effects on human health.

[Study on the occupational exposure limit of glyphosate in the air of workplace].

Objective: To establish occupational exposure limits for glyphosate in workplace air. Methods: In November 2014, by searching the documents of the United States Environmental Protection Agency (EPA) on glyphosate toxicity, the toxicity data and clinical symptoms of glyphosate toxicity were collected through various literature databases, and the target organs of glyphosate toxicity were determined. A total of 5 representative production enterprises in Jiangsu Province and Shandong Province were selected for field investigation. A total of 968 people were selected as the study subjects, including 526 workers exposed to glyphosate as the contact group, and 442 off-site (such as financial, administrative, etc.) workers with enterprises as the control group. Health examination was carried out in the exposure group and the control group to observe the damage of target organs of workers with different exposure concentrations and determine the occupational exposure limit. Results: The main target organs of glyphosate are liver and kidney and its effect on cholinesterase activity. The time-weighted average concentration (TWA) of glyphosate exposure in the exposure group was <0.03~48.91 mg/m(3), and there were statistically significant differences in liver and renal function between the exposure group and the control group (P<0.05). When the concentration of glyphosate in the air was higher than 5 mg/m3, there was a statistically significant difference in the abnormal rate of renal function between the exposure group and the control group (P<0.05) . Conclusion: The study sets the occupational exposure limit of glyphosate as 5 mg/m(3). The safety of this standard conforms to the relevant requirements of toxicology and occupational disease epidemiology, and also conforms to the existing economic and technological level in my country, and is highly feasible.

[Toxic effects of long-term pesticides exposure and key gene discovery].

Objective: Bioinformatics methods were used to mine differentially expressed genes (DEGs) and enriched signal pathways induced by chronic pesticide exposure, and explore its potential pathogenic mechanisms and key genes. Methods: In July 2021, high-throughput gene expression profile data related to pesticide toxicity was downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. The samples were from American male farm workers who had been exposed to pesticides for a long time and other industry workers. The functional enrichment analysis of GO, KEGG and Geme Set Enrichment Analysis (GSEA) were performed by R package clusterProfiler. STRING, Cytoscape and other tools were applied to construct and visualize the protein interaction network. With the help of MCODE and Cytohubba plugins, gene function modules were obtained, and hub gene was screened out. Results: 189 DEGs were screened from GSE30335 dataset, including 101 up-regulated genes and 88 down-regulated genes. The results of GO, KEGG and GSEA were mainly enriched in biological functions such as regulation of neuron projection development, regulation of locomotion, ribosomal protein synthesis, and pathways related to complex nervous system diseases such as Parkinson's disease. And the comprehensive screening showed that KLF1 was the hub gene of pesticide exposure, with a fold change of 0.456 (t=-3.82, P=0.021) . Conclusion: Long term exposure to pesticides results in the differential expression of multiple genes in the exposed population, which may be involved in the pathological changes of nervous system by down regulating KLF1 and related biological pathways.

[Determination of acetochlor and its metabolites in urine using liquid chromatography-tandem mass spectrometry].

Objective: A method for the determination of acetochlor and its metabolites in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established. Methods: After cleaned-up by a HLB extraction cartridges, the urine was eluted with 1% acetic acid acetonitrile solution. The target compounds were separated by ACQUITY UPLC®HSS T3 Column (2.1 mm×100 mm×1.8 µm) by using 1% formic acid solution and acetonitrile as mobile phase with gradient elution program, and analyzed in positive electrospray ionization mode by liquid chromatography tandem mass spectrometry. Results: All the target compounds showed good linear relationships in the range of 1-50 µg/L, and the correlation coefficients (r) were higher than 0.997. The recoveries rates at three different spiked levels for all target compounds in blank matrices were 107.6%-129.1%, and the relative standard deviations (RSD) were 1.5%-9.9% (n=6) . The limits of detection and quantitation of the method were 0.04-0.11 µg/L and 0.15-0.42 µg/L, respectively, and target substances were detected in all urine samples from occupational exposure workers to acetochlor. Conclusion: This method is suitable for rapid screening and analysis of acetochlor and metabolites in urine with the advantages of accuracy, rapidity, simplicity, high sensitivity and good specificity.

[Analysis of clinical characteristics and prognostic factors in 40 cases of acute glyphosate poisoning].

Objective: To explore the clinical characteristics and prognostic factors of patients with acute glyphosate poisoning, and to provide reference for the comprehensive treatment and prognosis judgment of acute glyphosate poisoning. Methods: The complete hospitalized medical records data of 40 patients with acute glyphosate poisoning who were treated in the emergency department of Affiliated Hospital of Yangzhou University from 2014 to 2019 were collected in August 2020. According to the outcome during the follow-up period of 90 d after discharge from hospital, patients were divided into survival group (n=33) and treatment failure group (n=7) . The clinical characteristics of the two groups were analyzed. The influencing factors of prognosis were analyzed by binary logistic regression, and the receiver operating characteristic (ROC) curve was used to evaluate the value of white blood cell count level at admission to the prognosis of patients with acute glyphosate poisoning. Results: The average age of the 40 glyphosate poisoning patients was (57.70±19.72) years old, the oral dose was 100 (50, 200) ml, the hospital stay was 4.0 (1.0, 5.0) d, and the fatality rate was 17.5% (7/40) . The main clinical manifestations were the symptoms of the digestive tract, respiratory tract, cardiovascular system and nervous system. Logistic regression showed that white blood cell level at admission was an influencing factor for the prognosis of patients with acute glyphosate poisoning (OR=1.148, 95%CI: 1.124-1.791, P=0.003) . The ROC curve showed that the best diagnostic cut-off value of white blood cell level at admission to the prognosis of acute glyphosate poisoning was 14.65×10(9)/L, the area under the curve (AUC) was 0.9351. The sensitivity was 100.00%, and the specificity was 84.85%. Conclusion: High level of white blood cell at admission is a risk factor for the prognosis of acute glyphosate poisoning, and white blood cell level at admission has a certain predictive value for the prognosis of acute glyphosate poisoning.

[Study on the effect of occupational exposure to glyphosate on blood routine].

Objective: To investigate the effect of glyphosate on blood routine of occupational exposure population. Methods: The workers who were occupationally exposed to glyphosate were selected as exposure group, and administrative staffs who were not exposed to glyphosate were selected as control group. Occupational health examination was conducted on all the subjects, and personal monitoring was applied to detect the concentration of glyphosate in the air of workplace. Time weighted average (TWA) concentration was calculated by the result of determination. Statistical methods were employed to compare the difference of blood routine results between the contact group and the control group, as well as between different posts. Results: 178 glyphosate workers were included in the contact group, and 203 non-contact persons were included in the control group. There was no statistically significant difference in the equilibrium test between the two groups(P>0.05). The abnormal rate of blood routine in the exposure group and the control group were 70.8% and 69.0%, respectively, but the difference was not statistically significant (P>0.05). Compared with the control group, the red blood cell count and platelet distribution width difference (P<0.05) were significant difference. There was no significant difference between different positions (P>0.05). Conclusion: When TWA value is below 9.40 mg/m(3), glyphosate has effect on the results of platelet distribution width and red blood cell count, but has no effect on the abnormal rate of blood routine.

[Analysis on monitoring results of occupational hazards in Yangzhou city from 2014 to 2018].

Objective: To undersand the monitor of occupational hazards in the enterprises in the past 5 years, as well as the distribution of occupational disease hazards and their dynamic changes in their respective jurisdictions, for providing scientific basis for prevention and control of occupational diseases in relevant departments. Methods: Taking the method of cluster sampling, select the monitoring results of the occupational disease hazard factors commissioned by the Municipal Center for Disease Control and Prevention from 2014 to 2018 and the annual monitoring data of the network of the occupational hazard declaration system of the Safety Supervision Bureau, using chi-square test, trend Statistical analysis was performed by chi-square test or Fisher exact probability method. Results: There were 461 testing companies in the past 5 years, with a total of 15, 186 monitoring points and 43428 samples. The pass rate was 94.32% (14324/15186) . The pass rate was increasing year by year from 2014 to 2017 (P<0.05) ; The pass rate of various occupational disease hazards surveillance were greater than 90% except the rate of physical factors. In 2014, the qualified rate of physical factors was the lowest, which was 86.99% (1558/1791) ; the production rate of different production scale enterprises in 2018 was higher than that of 2014. From 2014 to 2018, the number of inspection enterprises and the number of inspection points of the joint-stock economy and state-owned economic enterprises are both high, 58 (10091 points) and 71 (1830 points) respectively; The qualified rate of state-owned economy and collective economy monitoring is high, 98.36% (1800/1830) and 100% (74/74) respectively. It had reached more than 95%; The enterprises tested mainly from the economic development zone and Guangling, respectively accounting for 34.27% (158/461) and 33.84% (156/461) of the total number of enterprises. Which followed by the Hanjiang, accounting for 23.21% of the total number of enterprises (107/461) ; The monitoring enterprises were mainly distributed in the manufacturing and power industries, which accounted for 85.25% (393/461) and 6.07% (28/461) of the total number of enterprises, respectively. Conclusion: The monitoring rate of enterprises had been increasing year by year from 2014 to 2018. Noise was the main disease prevention and controlling factor in the area.In addition, micro-enterprises, individual economy and foreign-invested economy were the key targets for occupational health.