Carbon disulfide induces accumulation of TDP-43 in the cytoplasm and mitochondrial dysfunction in rat spinal cords.

The relationship between environmental neurotoxicant exposure and neurodegenerative diseases is being extensively investigated. Carbon disulfide, a classic neurotoxicant and prototype of dithiocarbamates fungicides and anti-inflammatory agents, has been detected in urban adults, raising questions about whether exposure to carbon disulfide is associated with a high incidence of neurodegenerative diseases. Here, using rat models and SH-SY5Y cells, we investigated the possible mechanistic linkages between carbon disulfide neurotoxicity and the expression of TDP-43 protein, a marker of amyotrophic lateral sclerosis/frontotemporal lobar degeneration. Our results showed that rats exhibited severe dyskinesia and increased TDP-43 expression in the spinal cord following carbon disulfide exposure. Moreover, carbon disulfide exposure induced abnormal cytoplasmic localization and phosphorylation of TDP-43 in motor neurons. Importantly, carbon disulfide treatment led to the accumulation of TDP-43 in the mitochondria of motor neurons and resulted in subsequent mitochondrial damage, including mitochondrial structural disruption, mitochondrial respiratory chain complex I inhibition, and impaired VCP/p97-dependent mitophagy. In summary, our study provides support for carbon disulfide exposure-mediated TDP-43 mislocalization and mitochondrial dysfunction, contributes to understanding the pathogenesis of environmental neurotoxin-induced neurodegeneration, and provides inspiration for potential therapeutic strategies.

Carbon disulfide removal from gasoline fraction using zinc-carbon composite synthesized using microwave-assisted homogenous precipitation.

Carbon disulfide (CS2) is one of the sulfur components that are naturally present in petroleum fractions. Its presence causes corrosion issues in the fuel facilities and deactivates the catalysts in the petrochemical processes. It is a hazardous component that negatively impacts the environment and public health due to its toxicity. This study used zinc-carbon (ZC) composite as a CS2 adsorbent from the gasoline fraction model component. The carbon is derived from date stone biomass. The ZC composite was prepared via a homogenous precipitation process by urea hydrolysis. The physicochemical properties of the prepared adsorbent are characterized using different techniques. The results confirm the loading of zinc oxide/hydroxide carbonate and urea-derived species on the carbon surface. The results were compared by the parent samples, raw carbon, and zinc hydroxide prepared by conventional and homogeneous precipitation. The CS2 adsorption process was performed using a batch system at atmospheric pressure. The effects of adsorbent dosage and adsorption temperatures have been examined. The results indicate that ZC has the highest CS2 adsorption capacity (124.3 mg.g-1 at 30 °C) compared to the parent adsorbents and the previously reported data. The kinetics and thermodynamic calculation results indicate the spontaneity and feasibility of the CS2 adsorption process.

Carbon disulfide exposure induced lung function reduction partly through oxidative protein damage: A cross-sectional and longitudinal analysis.

Carbon disulfide (CS2) exposure has been associated with lung function reduction in occupational population. However, evidence on the general population with relatively low CS2 exposure is lacking and the mechanism involved remains largely unknown. Urinary CS2 metabolite (2-mercaptothiazolidine-4-carboxylic acid, TTCA) and lung function were determined in the urban adults from the Wuhan-Zhuhai cohort at baseline in 2011-2012 and were repeated every 3 years. Cross-sectional and longitudinal associations between TTCA and lung function were estimated using linear mixed models. Inflammation and oxidative damage biomarkers in blood/urine were measured to evaluate their potential mediating roles involved. Cross-sectionally, participants in the highest quartile of TTCA level showed a 0.64% reduction in FEV1/FVC and a -308.22 mL/s reduction in PEF, compared to those in the lowest quartile. Longitudinally, participants with consistently high TTCA level had annually -90.27 mL/s decline in PEF, compared to those with consistently low TTCA level. Mediation analysis revealed that plasma protein carbonyl mediated 49.89% and 22.10% of TTCA-associated FEV1/FVC and PEF reductions, respectively. Conclusively, there was a cross-sectional and longitudinal association between CS2 exposure and lung function reduction in the general urban adults, and protein carbonylation (oxidative protein damage) partly mediated lung function reduction from CS2 exposure.

DNA Damage on Buccal Epithelial Cells, Personal Working in the Rubber Industry Occupationally Exposed to Carbon Disulfide (CS2).

INTRODUCTION: The most significant industrial utilization of carbon disulfide (CS2) has been in the manufacture of cellulose rayon, cellophane, and rubber industry. CS2 prompts expanded recurrence of chromosomal variations in laborers occupationally exposed to CS2. MATERIALS AND METHODS: In the current study, the DNA analysis was carried out from exfoliated buccal epithelial cells from rubber industry workers exposed to CS2 and an equal number of healthy control subjects. Both the control and experimental subjects were categorized by their smoking habits such as smokers (S) and non-smokers (NS). Furthermore, experimental subjects were further separated based on their exposure period. Students t-test statistical tools were used to analyze the final results. RESULTS: The present analysis identified a high frequency of DNA damage in rubber industry workers (16.55±0.43) than control subjects (9.8±0.21). Also, maximum number of DNA damage detected in smoking experimental group (18.27±0.02) than non-smoking experimental (15.02±0.01) and smoking control groups (10.25±0.04 ). CONCLUSION: Smoking habits synergistically increased the DNA damage in the rubber industry workers exposed to CS2.

NaH-promoted one-pot synthesis of 5-amidoimidazoles from arylamines, carbon disulfide and isocyanides.

A novel, convenient and efficient protocol to access functionalized 5-amidoimidazoles is developed via one-pot synthesis from readily available materials of arylamines, carbon disulfide and isocyanides. The transformation was realized at room temperature and provided 5-amidoimidazoles in moderate to good yields in the presence of NaH. In addition, control experiments indicated that the process might be achieved via the base-induced cyclization of activated methylene isocyanides with N,N-disubstituted thioureas that produced from the reaction of amines and carbon disulfide.

Concerted and sequential three-body fragmentation of deep-core-ionized carbon disulfide.

Momentum vector correlation is a powerful tool to study molecular dissociation. We have studied the three-body fragmentation of carbon disulfide after sulfur 1s photoionization by means of momentum imaging techniques. Concerted and sequential pathways are disentangled in three-body fragmentation using adapted analysis strategies. In particular, we introduce various data visualization schemes that are proved to be particularly efficient to determine dissociation dynamics.

[Characterization of VOCs Emissions from Caged Broiler House in Winter].

Volatile organic compound (VOCs) emissions from poultry and livestock facilities affect the surrounding environmental quality and human health. However, VOCs emissions from broiler houses have been less characterized, and studies of related dominant odorants, carcinogenic risk, and ozone formation potential are still lacking. To fill this research gap, VOCs pollutants emitted from a broiler house were investigated in this study. The VOCs emission characteristics of the broiler house during three different periods of broiler growth (early, middle, and later) were analyzed using gas chromatography-mass spectrometry. The results showed that 77 types of VOCs were detected, including 16 types of halogenated hydrocarbons, 21 types of alkanes, 5 types of olefins, 12 types of aromatic hydrocarbons, 15 types of oxygenated volatile organic compounds (OVOCs), and 8 types of sulfides. During the entire 42-day growth period, the concentrations of halogenated hydrocarbons, alkanes, olefin, aromatic hydrocarbons, and OVOCs in the broiler house showed few changes. However, with the growth of broilers, the intake of sulfur-containing amino acids and the fecal emission coefficient increased, resulting in the gradual conversion of the VOCs to sulfide. Therefore, emissions of sulfur-containing VOCs increased in the early and middle growth periods. Moreover, the increase in ventilation in the house during the later growth period resulted in a decrease in the sulfur-containing VOCs concentrations. The dominant odorants in the broiler house were naphthalene, ethyl acetate, acetaldehyde, carbon disulfide, dimethyl disulfide, methanethiol, methanethiol, and thiophene. Methanethiol had the highest odorous values, ranging from 2172.4 to 19090.9. Meanwhile, there were acceptable levels of carcinogenic risk in the early and middle growth periods, with a lifetime cancer risk (LCR) of 7.7×10-6 and 4.5×10-6, respectively. The average ozone formation potential (OFP) was (1458.9±787.4) µg·m-3. The results of this study can provide a scientific basis for the monitoring of malodorous substances and formulation of emission reduction strategies in broiler production.

Synthesis and Biological Importance of 2-(thio)ureabenzothiazoles.

The (thio)urea and benzothiazole (BT) derivatives have been shown to have a broad spectrum of biological activities. These groups, when bonded, result in the 2-(thio)ureabenzothizoles (TBT and UBT), which could favor the physicochemical and biological properties. UBTs and TBTs are compounds of great importance in medicinal chemistry. For instance, Frentizole is a UBT derivative used for the treatment of rheumatoid arthritis and systemic lupus erythematosus. The UBTs Bentaluron and Bethabenthiazuron are commercial fungicides used as wood preservatives and herbicides in winter corn crops. On these bases, we prepared this bibliography review, which covers chemical aspects of UBTs and TBTs as potential therapeutic agents as well as their studies on the mechanisms of a variety of pharmacological activities. This work covers synthetic methodologies from 1935 to nowadays, highlighting the most recent approaches to afford UBTs and TBTs with a variety of substituents as illustrated in 42 schemes and 13 figures and concluded with 187 references. In addition, this interesting review is designed on chemical reactions of 2-aminobenzothiazoles (2ABTs) with (thio)phosgenes, iso(thio)cyanates, 1,1'-(thio)carbonyldiimidazoles [(T)CDI]s, (thio)carbamoyl chlorides, and carbon disulfide. This topic will provide information of utility for medicinal chemists dedicated to the design and synthesis of this class of compounds to be tested with respect to their biological activities and be proposed as new pharmacophores.

Emission of volatile sulphur compounds during swine manure composting: Source identification, odour mitigation and assessment.

This study aimed to identify the sources of volatile sulphur compounds (VSCs) and evaluate their mitigation by ferric oxide (Fe2O3) during swine manure composting. Four chemicals, including l-cysteine, l-methionine, sodium sulphite, and sodium sulphate, were further added to simulate organic and inorganic sulphur-containing substances in swine manure to track VSC sources during composting. Results show that sulphur simulants induced the emission of six common VSCs, including methyl sulphide (Me2S), dimethyl sulphide (Me2SS), carbonyl sulphide (COS), carbon disulphide (CS2), methyl mercaptan (MeSH), and ethyl mercaptan (EtSH), during swine manure composting. Of them, COS, CS2, MeSH and Me2SS were predominantly contributed by the biodegradation of methionine and cysteine, while Me2S and EtSH were dominated by the reduction of sulphite and sulphate. Further Fe2O3 addition at 1.5 % of total wet weight of composting materials immobilized elemental sulphur and inhibited sulphate reduction to reduce the emission of VSCs by 46.7-80.9 %. Furthermore, odour assessment indicated that adding Fe2O3 into composting piles significantly reduced the odour intensity level to below 4, the odour value of VSCs by 47.1-81.3 %, and thus the non-carcinogenic risk by 68.4 %.

Synthesis of functionalized S-benzyl dithiocarbamates from diazo-compounds via multi-component reactions with carbon disulfide and secondary amines.

Triflic acid promoted multi-component synthesis of functionalized S-benzyl dithiocarbamates from diazo compounds, carbon disulfide and secondary amines is reported. The reactions proceeded at room temperature and gave the desired dithiocarbamates in good yields. Wide-substrate scope and easy operation are the important features of this methodology.

Occupational risk factors for hypertension.

The identification and characterization of the modifiable risk factors of hypertension is of great value for public health and clinical medicine to achieve primary prevention. A large amount of literature on the effects of occupational factors on blood pressure and hypertension has been published. In this review, I summarize current evidence regarding the role of occupational factors in hypertension. The results of this review suggest that there is sufficient evidence to support the association between increased risk of hypertension and job stress, shift work, occupational lead exposure, and noise exposure. The association of hypertension with physical inactivity, sedentary behavior, and occupational exposure to mercury, arsenic, cadmium, or carbon disulfide remains inconclusive, although several studies have reported this finding. This review will serve as a step toward future research and provide baseline information for developing strategic interventions to prevent hypertension in the working population.

Molecular Simulation to Explore the Dissolution Behavior of Sulfur in Carbon Disulfide.

Soluble sulfur (S8) and insoluble sulfur (IS) have different application fields, and molecular dynamics simulation can reveal their differences in solubility in solvents. It is found that in the simulated carbon disulfide (CS2) solvent, soluble sulfur in the form of clusters mainly promotes the dissolution of clusters through van der Waals interaction between solvent molecules (CS2) and S8, and the solubility gradually increases with the increase in temperature. However, the strong interaction between polymer chains of insoluble sulfur in the form of polymer hinders the diffusion of IS into CS2 solvent, which is not conducive to high-temperature dissolution. The simulated solubility parameter shows that the solubility parameter of soluble sulfur is closer to that of the solvent, which is consistent with the above explanation that soluble sulfur is easy to dissolve.

Chromatographic analysis of dithiocarbamate residues and their metabolites in foods employed in dietary exposure studies-a review.

Dithiocarbamates (DTCs) belong to a group of compounds used as fungicides in food production and can be divided into three major groups. Since DTCs easily oxidise and hydrolyse in alkaline and acidic medium respectively, precautions have to be implemented during preparation/homogenisation and extraction of samples. As such, test samples are commonly prepared individually by cutting into small pieces just before the digestion of DTCs with a hot acid to give carbon disulphide (CS2) and the results are expressed as CS2 without any differentiation of individual DTCs. However, individual DTCs have different toxicological potencies whilst their metabolites are more toxic than the parent compound. Apart from the hot digestion method, chromatographic separation of three major groups of DTCs has been developed by a number of different researchers. This review provides a comprehensive examination of sample preparation, extraction, clean-up and chromatographic methods for the determination of individual DTCs and their more toxic metabolites in foodstuffs. Moreover, this review also studies on how dietary exposure of DTCs can be efficiently and effectively estimated using different methods of analysis.

False positive effect of sulfur sources used in growing and processing of vine (Vitis Vinifera L.) leaves on the results of dithiocarbamate analysis based on carbon disulfide measurement.

Vine leaves, which are produced fresh, brined or fermented from the leaves of Vitis Vinifera in Türkiye are an important food. Sulfur is used as a pesticide and sulfur compounds can be used as additives during the growing and processing of the vine leaves. These sulfur sources cause positive results on carbon disulfide (CS2) measurements by GC-MS. Therefore, the main objective of the present study was to investigate the effects of residues of sulfur or sulfur compounds on dithiocarbamate analysis methods based on CS2 measurement. For this, vine leaves were produced by controlled agricultural production and processed as brine under controlled conditions. The sulfur dioxide (SO2) and dithiocarbamate analysis were carried out on the vine leave obtained by applying sulfur spraying in agricultural treatments and brined vine leaves produced by adding sodium metabisulfite (SM), and control samples of each stage. SO2 was not detected in any of the samples in this study. SO2 residues did not occur in the vine leaves as a result of the sulfur spraying application and therefore did not have a false positive effect on dithiocarbamate analysis. However, approximately 0.15 mg kg-1 false positive dithiocarbamate was detected, which is thought to originate from natural sulfur in the vine leaves. The effect of SM, which was used in low concentration in the production of brined vine leaves, on dithiocarbamate results was limited. Even if SM was not used, the total false positive dithiocarbamate result in the brined vine leaves production process was approximately determined as 0.20 mg kg-1. This study showed that the dithiocarbamates analysis method based on CS2 measurement may lead to false positive results in brined vine leaves since sulfur compounds are found naturally in vine leaves.

[Study on determination of 2-thioxothiazolidine-4-carboxylic Acid in urine by high performance liquid chromatography].

Objective: To establish a high performance liquid chromatography method for the determination of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: After acidification with hydrochloric acid, TTCA in urine was first extracted by ethyl acetate with excessive sodium chloride, then gradient separated by a symmetry C18 column and then detected by a diode array detector. The quantification was based on a working curve of external standard method. Results: The linear relationship of TTCA in urine was good in the range of 0.03-10.00 mg/L, and the correlation coefficient was 0.9999. The detection limit and minimum quantitative concentration of TTCA in urine were 0.008 mg/L and 0.027 mg/L. The intra-assay precision of the method was 0.9%-1.4%, the inter-assay precision was 1.3%-3.5%, and the average recovery was 85.0%-92.7% while the concentrations of TTCA in urine was 0.8, 2.0 and 8.0 mg/L, respectively (n=6) . Conclusion: The gradient elution high performance liquid chromatography method has simple operation and high sensitivity, and it is suitable for the determination of TTCA on a low level in urine for occupational workers exposure to carbon disulfide.

Volatile organic compounds emission in the rubber products manufacturing processes.

Volatile organic compounds (VOCs) emission from rubber products manufacture processes, mixing, shaping and vulcanization were investigated in four rubber products factories in China. The source emission air was passively sampled by pre-vacuumized stainless steel canister and analyzed by gas chromatography-mass spectrometry-flame ionization detection (GC/MS-FID). The species profile of 107 VOCs in the emission processes were obtained. We calculated the photochemical ozone formation potential (OFP) and carcinogenic risk (CR) of the VOCs for each manufacture process. The results showed that mixing process mainly released dichloromethane (14.53%), carbon disulfide (CS2) (6.88%), styrene (5.72%), 4-methyl-2-pentanone (5.22%) and naphthalene (3.69%) for solvents used and raw rubber degradation in the process. The C6-C8 alkanes, especially heptane and isomers of heptane (44.71%), were dominated in shaping process. The major species released from vulcanization process were carbon disulfide (29.72%), naphthalene (8.17%), acetone (7.73%) and dichloromethane (4.26%). VOCs emitted from vulcanization process had the highest OFP, which contributed by naphthalene, m/p-xylene, o-xylene and carbon disulfide. VOCs emission from mixing process had the highest CR, and 1,2-dibromoethane, 1,2-dichlorethane and 1,3-butadiene were the main contributors to CR. We also estimated the total VOCs emissions into the atmosphere from tires manufacturing in China, which were 7.58 × 105 t in 2018 and contributed about 9% of total industry processes VOCs emissions.

Base-Promoted Formal [3 + 2] Cycloaddition of α-Halohydroxamates with Carbon Disulfide to Synthesize Polysubstituted Rhodanines.

A concise and practical strategy via potassium-carbonate-mediated [3 + 2]-cycloaddition reaction of α-halohydroxamates with the common solvent carbon disulfide for the synthesis of functionalized rhodanine derivatives in good to excellent yields is developed. The present methodology features a wide substrate scope as well as good functional group tolerance. The potential synthetic utility of this protocol is demonstrated by synthesis of a series of natural product derivatives containing rhodamine skeletons.

How to Differentiate General Toxicity-Related Endocrine Effects from Endocrine Disruption: Systematic Review of Carbon Disulfide Data.

This review provides an overview of the assessment of the endocrine disrupting (ED) properties of carbon disulfide (CS2), following the methodology used at the European level to identify endocrine disruptors. Relevant in vitro, in vivo studies and human data are analyzed. The assessment presented here focuses on one endocrine activity, i.e., thyroid disruption, and two main adverse effects, neurotoxicity and cardiotoxicity. The data available on the different ED or non-ED modes of action (MoA), known to trigger these adverse effects, are described and the strength of evidence of the different MoA is weighted. We conclude that the adverse effects could be due to systemic toxicity rather than endocrine-mediated toxicity. This assessment illustrates the scientific and regulatory challenges in differentiating a specific endocrine disruption from an indirect endocrine effect resulting from a non-ED mediated systemic toxicity. This issue of evaluating the ED properties of highly toxic and reactive substances has been insufficiently developed by European guidance so far and needs to be further addressed. Finally, this example also raises questions about the capacity of the technics available in toxicology to address such a complex issue with certainty.

Design and synthesis of novel nitrothiazolacetamide conjugated to different thioquinazolinone derivatives as anti-urease agents.

The present article describes the design, synthesis, in vitro urease inhibition, and in silico molecular docking studies of a novel series of nitrothiazolacetamide conjugated to different thioquinazolinones. Fourteen nitrothiazolacetamide bearing thioquinazolinones derivatives (8a-n) were synthesized through the reaction of isatoic anhydride with different amine, followed by reaction with carbon disulfide and KOH in ethanol. The intermediates were then converted into final products by treating them with 2-chloro-N-(5-nitrothiazol-2-yl)acetamide in DMF. All derivatives were then characterized through different spectroscopic techniques (1H, 13C-NMR, MS, and FTIR). In vitro screening of these molecules against urease demonstrated the potent urease inhibitory potential of derivatives with IC50 values ranging between 2.22 ± 0.09 and 8.43 ± 0.61 µM when compared with the standard thiourea (IC50 = 22.50 ± 0.44 µM). Compound 8h as the most potent derivative exhibited an uncompetitive inhibition pattern against urease in the kinetic study. The high anti-ureolytic activity of 8h was confirmed against two urease-positive microorganisms. According to molecular docking study, 8h exhibited several hydrophobic interactions with Lys10, Leu11, Met44, Ala47, Ala85, Phe87, and Pro88 residues plus two hydrogen bound interactions with Thr86. According to the in silico assessment, the ADME-Toxicity and drug-likeness profile of synthesized compounds were in the acceptable range.

Influence of dissolved organic matter on carbonyl sulfide and carbon disulfide formation from dimethyl sulfide during sunlight photolysis.

Carbonyl sulfide (COS) and carbon disulfide (CS2 ) are important atmospheric gases photochemically generated from organic sulfur precursors in sunlit natural waters. This study examined these processes by evaluating COS and CS2 photoproduction from dimethyl sulfide (DMS) in the presence of dissolved organic matter (DOM). DOM was added because it photochemically produces various reactive intermediates (3 CDOM*, • OH, 1 O2 , and H2 O2 ) potentially involved in these reaction pathways. DMS-amended synthetic waters at pH 8 were varied in terms of their DOM type and concentration, spiked with the 3 CDOM* quenching agent, phenol, in certain cases, and subsequently irradiated over varying exposure times. Results indicated that various DOM types ranging from freshwater to open-ocean DOM increased COS but did not alter CS2 , which remained at nondetect levels. DOM type influenced COS only at higher concentrations (20 mg/L), whereas increasing DOM concentrations proportionally increased COS concentrations for all DOM types. Phenol addition lowered COS formation for reasons that remained unclear because phenol likely quenched 3 CDOM* and DMS-derived sulfur-based radicals. Further comparisons with DMS-spiked natural waters and cysteine (CYS)-spiked synthetic and natural waters assessed previously indicated that COS formation from both precursors in natural waters was always greater than in waters containing DOM alone. PRACTITIONER POINTS: DMS- and DOM-spiked synthetic waters formed COS but did not form CS2 during sunlight photolysis. In DMS-spiked synthetic solutions, DOM type has a limited influence on COS formation whereas DOM concentration has a stronger influence on COS formation. COS formation in the DMS-spiked synthetic waters was fairly proportional to the DOC concentration but was generally lower than COS formation in DMS-spiked natural waters.