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Environmental Science and Pollution... Jun 2024Most of the individual and/or amalgamated compounds present in the atmospheric air are not known for their toxicologic potential and impact on human health. The...
Most of the individual and/or amalgamated compounds present in the atmospheric air are not known for their toxicologic potential and impact on human health. The toxicologic strength of methyl isocyanate (MIC) gas was unknown till its accidental leakage that instantly claimed thousands of lives. Cytogenetic study showed increased chromosome aberrations (CA) and sister chromatid exchanges (SCEs) and delayed cell replication index (RI) in a multicentre genetic screening program on gas victims immediate post-disaster. A surveillance study after 30 years displayed reduction in CA compared to the initial status in survivors of the severely and moderately exposed strata. Altogether, cytogenetic damage was significantly predominant in the severely exposed population. Stable and replicable aberrations and chromatid exchanges were detected in both studies, which collectively indicate genetic instability. The variation in individual cytogenetic spectrum from similar exposure status could be the result of inter-individual response to the external factors over 30 years post-disaster. The spectrum of CA detected after 30 years might be the cumulative effect of occupational, environmental and life-style factors at a background of one episode of acute MIC exposure. Had MIC's toxicologic potential was known before, fatality and health effects could have been averted. In vitro assessment of toxicity of tin showed a positive correlation with dose and age of exposure, which was aggravated by smoking. Age has shown a significant effect on CA in the general population. The present report recommends evaluation of toxicity prior to use, and reduction of pollution at source for a maintaining a sustainable environmental context.
Topics: Humans; Chromosome Aberrations; Accidents, Occupational; Isocyanates; Sister Chromatid Exchange; Mutagens
PubMed: 37442927
DOI: 10.1007/s11356-023-28681-9 -
Mymensingh Medical Journal : MMJ Jul 2023Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two nosocomial infection causing pathogens,...
Antibacterial Effects of Chloroform Henna (Lawsonia inermis) Leaf Extracts against Two Nosocomial Infection Causing Pathogens: Gram-positive Staphylococcus aureus and Gram-negative Klebsiella pneumoniae: A Comparative Study.
Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae. This interventional study was carried out for the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh. The antibacterial activity was tested at different concentrations of Chloroform Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents chloroform and 0.1% Dimethyl sulfoxide (DMSO). The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Chloroform extracts. Chloroform Henna Extracts (CHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000 mg/ml). Among different concentrations of the CHE, 100mg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and Klebsiella pneumoniae. The MIC for Staphylococcus aureus and Klebsiella pneumoniae were 100 and 200mg/ml in CHE respectively. The MIC of Ciprofloxacin was 1μg/ml against Staphylococcus aureus and 1.5μg/ml against Klebsiella pneumoniae. The MIC of Ciprofloxacin was the lowest in comparison to MICs of CHE for the test organisms. This study showed that Chloroform Henna extracts demonstrated antibacterial effects against food borne pathogens. It is clearly observed that there is definite antibacterial effect of the Chloroform extract of Henna leaves (Lawsonia inermis) against Staphylococcus aureus and Klebsiella pneumoniae.
Topics: Humans; Cross Infection; Chloroform; Klebsiella pneumoniae; Lawsonia Plant; Staphylococcus aureus; Staphylococcal Infections; Anti-Bacterial Agents; Ciprofloxacin; Plant Extracts
PubMed: 37391949
DOI: No ID Found -
Pharmaceuticals (Basel, Switzerland) Jan 2023On the basis of previous reports, novel 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase...
On the basis of previous reports, novel 2-benzoylhydrazine-1-carboxamides were designed as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibitors of these enzymes have many clinical applications. 2-(Substituted benzoyl)hydrazine-1-carboxamides decorated with -methyl or tridecyl were prepared with three methods from commercially available or self-prepared hydrazides and isocyanates. For methyl derivatives, -succinimidyl -methylcarbamate was used or methyl isocyanate was prepared via Curtius rearrangement. Tridecyl isocyanate was synthesized again via Curtius rearrangement or from triphosgene and tridecylamine. The compounds were evaluated for the inhibition of AChE and BChE using Ellman's spectrophotometric method. Most of the derivatives showed the dual inhibition of both enzymes with IC values of 44-100 µM for AChE and from 22 µM for BChE. In general, the carboxamides inhibited AChE more strongly. A large number of the compounds showed better or quite comparable inhibition of cholinesterases in vitro than that of the drug rivastigmine. Molecular docking was performed to investigate the possible conformation of the compounds and their interactions with target enzymes. In both AChE and BChE, the compounds occupied the enzyme active cavity, and, especially in the case of BChE, the compounds were placed in close proximity to the catalytic triad.
PubMed: 37259322
DOI: 10.3390/ph16020172 -
Antimicrobial Agents and Chemotherapy May 2023Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including...
Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. susceptibility of isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent activity against all C. auris isolates (MIC range: 0.008 to 0.015 μg/mL [CLSI]; 0.004-0.03 μg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.
Topics: Humans; Male; Female; Antifungal Agents; Candidemia; Candida auris; Candidiasis, Invasive; Treatment Outcome; Microbial Sensitivity Tests
PubMed: 37022196
DOI: 10.1128/aac.01419-22 -
Fire Technology 2023Firefighters' or instructors' exposure to airborne chemicals during live-fire training may depend on fuels being burned, fuel orientation and participants' location...
Firefighters' or instructors' exposure to airborne chemicals during live-fire training may depend on fuels being burned, fuel orientation and participants' location within the structure. This study was designed to evaluate the impact of different control measures on exposure risk to combustion byproducts during fire dynamics training where fuel packages are mounted at or near the ceiling. These measures included substitution of training fuels (low density wood fiberboard, oriented strand board (OSB), pallets, particle board, plywood) and adoption of engineering controls such as changing the location of the instructor and students using the structure. Experiments were conducted for two different training durations: the typical six ventilation cycle (6-cycle) and a shorter three ventilation cycle (3-cycle) with a subset of training fuels. In Part A of this series, we characterized the fire dynamics within the structure, including the ability of each fuel to provide an environment that achieves the training objectives. Here, in Part B, airborne chemical concentrations are reported at the location where fire instructors would typically be operating. We hypothesized that utilizing a training fuel package with solid wood pallets would result in lower concentrations of airborne contaminants at the rear instructor location than wood-based sheet products containing additional resins and/or waxes. In the 6-cycle experiments (at the rear instructor location), OSB-fueled fires produced the highest median concentrations of benzene and 1,3 butadiene, plywood-fueled fires produced the highest total polycyclic aromatic hydrocarbon (PAH) concentrations, particle board-fueled fires produced the highest methyl isocyanate concentrations, and pallet-fueled fires produced the highest hydrogen chloride concentrations. All fuels other than particle board produced similarly high levels of formaldehyde at the rear instructor location. The OSB fuel package created the most consistent fire dynamics over 6-cycles, while fiberboard resulted in consistent fire dynamics only for the first three cycles. In the follow-on 3-cycle experiment, PAH, benzene, and aldehyde concentrations were similar for the OSB and fiberboard-fueled fires. Air sampling did not identify any clear differences between training fires from burning solid wood pallets and those that incorporate wood-based sheet products . However, it was found that exposure can be reduced by moving firefighters and instructors lower in the compartment and/or by moving the instructor in charge of ventilation from the rear of the structure (where highest concentrations were consistently measured) to an outside position.
PubMed: 38650825
DOI: 10.1007/s10694-023-01447-y -
Journal of Chromatography. A Oct 2022Methyl isocyanate (MIC), an intermediate in the synthesis of carbamate pesticides, is a toxic industrial chemical that causes irritation and damage to the eyes,...
Methyl isocyanate (MIC), an intermediate in the synthesis of carbamate pesticides, is a toxic industrial chemical that causes irritation and damage to the eyes, respiratory tract, and skin. Due to the high reactivity of MIC, it binds to proteins to form protein adducts. While these adducts can be used as biomarkers to verify exposure to MIC, methods to detect MIC adducts are cumbersome, typically involving enzymatic (pronase) or strong acid (Edman degradation) hydrolysis of hemoglobin. Hence, in this study, a simple method was developed which utilizes base hydrolysis of MIC-tyrosine adducts from isolated hemoglobin to form phenyl methyl carbamate (PMC), followed by rapid liquid-liquid extraction, and liquid chromatography tandem mass spectrometry analysis. The hydrolysis chemistry is the first report of base hydrolysis of a tyrosine-β-C-hydroxo phenol bond in aqueous solution. The method produced excellent sensitivity (detection limit of 0.02 mg/kg), linearity (R = 0.998, percent residual accuracies > 96), and dynamic range (0.06‒15 mg/kg). The accuracy and precision (100 ± 9% and < 10% relative standard deviation, respectively) of the method were outstanding compared to existing techniques. The validated method was able to detect significantly elevated levels of PMC from hemoglobin isolated from MIC-exposed rats.
Topics: Animals; Biomarkers; Carbamates; Hemoglobins; Isocyanates; Pesticides; Phenols; Pronase; Rats; Tyrosine
PubMed: 36099696
DOI: 10.1016/j.chroma.2022.463454 -
Environmental Science and Pollution... Jan 2023Immediate assessment of genetic damage in methyl isocyanate (MIC) gas-exposed population in small and heterogeneous samples using diversified study designs and...
Spectrum of stable and unstable rearrangements in lymphocytic chromosomes investigated in Bhopal population 30 years post MIC disaster amid co-exposure to lifestyle, living, and occupational hazards.
Immediate assessment of genetic damage in methyl isocyanate (MIC) gas-exposed population in small and heterogeneous samples using diversified study designs and solid-stained metaphases could not depict the actual genetic impact of MIC on accidentally exposed individuals. The outcome of the then large multi-center genetic screening program was not available to the public and scientific community. Also, the routine and regular epidemiological health survey does not capture the genetic and long-term effect of MIC. Therefore, genetic screening was carried out 30 years post disaster during 2015-2017 with a view to screen the present status of chromosomal consequences in lymphocytic cells. Participants were recruited from moderate (34) and severely (78) exposed and unexposed (35) cohorts with their informed consent. Analysis of ~100 mitotic cells and karyotyping of at least 10-15 and all abnormal metaphases detected structural and numerical alterations, including stable and replicable ones. Clonal abnormalities were detected with monosomal and complex karyotypes, trisomy 8, del5q/20q, loss of Y, etc. Among all, X-chromosome was frequently involved in numerical alterations. Structural aberrations appeared higher in the then exposed populations, though abnormalities cannot be linked directly to MIC exposure 30 years post disaster. Collectively, all rearrangements were markedly higher in the severely exposed population. Altogether, the detected abnormalities appeared random and indicated genomic instability, suggesting follow-up at shorter intervals for the individuals detected with clonal aberrations. G-banding has facilitated recognition of chromosomal involvement and their breakpoints and classification of structural rearrangements. The present data has been derived from the 30-year post-disaster genetic screening.
Topics: Humans; Isocyanates; Chromosomes; Disasters; Life Style; Chromosome Aberrations
PubMed: 35922599
DOI: 10.1007/s11356-022-22053-5 -
Bulletin of the World Health... Apr 2022Multiple environmental health issues resulting from pollution and climate change threaten public health in India.
PROBLEM
Multiple environmental health issues resulting from pollution and climate change threaten public health in India.
APPROACH
The Government of India recognized the need for a permanent environmental health research institute; the Indian Council of Medical Research therefore established the National Institute for Research in Environmental Health in Bhopal in 2010. Scientists at the institute assessed the multiple long-term health effects of exposure to methyl isocyanate, and are now conducting research on a wide array of locally relevant environmental health issues.
LOCAL SETTING
The Union Carbide India Limited pesticide factory in Bhopal was the site of a methyl isocyanate gas leak in 1984, which affected half a million people. The Indian Council of Medical Research set up a coordinating unit in the immediate aftermath, which was upgraded to the Bhopal Gas Disaster Research Centre in 1986 and then the Centre for Rehabilitation Studies in 1995.
RELEVANT CHANGES
Scientists at the institute undertake environmental monitoring and health risk assessment studies among communities located near polluted areas, such as industrial areas. They are also assessing the training needs of practising physicians, with the aim of developing a curated curriculum to meet the deficiencies in environmental health education in the country.
LESSONS LEARNT
Environmental legislation was introduced in the wake of the disaster and a research institute in environmental health was established. Researchers at the institute have recognized the importance of engaging communities in environmental health research, as well as knowledge dissemination to relevant stakeholders.
Topics: Academies and Institutes; Environmental Exposure; Environmental Health; Environmental Pollution; Humans; India; Industry
PubMed: 35386553
DOI: 10.2471/BLT.21.286680 -
Environment International Apr 2022We report on the concentration ranges and combustion source-related emission profiles of organic and inorganic species released during 34 major industrial fires in the...
We report on the concentration ranges and combustion source-related emission profiles of organic and inorganic species released during 34 major industrial fires in the UK. These episodic events tend to be acute in nature and demand a rapid public health risk assessment to indicate the likely impact on exposed populations. The objective of this paper is to improve our understanding of the nature, composition and potential health impacts of emissions from major incident fires and so support the risk assessment process. Real world monitoring data was obtained from portable Fourier Transform Infrared (FTIR) monitoring (Gasmet DX-4030/40) carried out as part of the UK's Air Quality in Major Incidents service. The measured substances include carbon monoxide, sulphur dioxide, nitrogen dioxide, ammonia, hydrogen chloride, hydrogen bromide, hydrogen fluoride, hydrogen cyanide, formaldehyde, 1,3-butadiene, benzene, toluene, xylenes, ethyl benzene, acrolein, phosgene, arsine, phosphine and methyl isocyanate. We evaluate the reported concentrations against Acute Exposure Guideline Values (AEGLs) and Emergency Response Planning Guidelines (ERPGs), as well as against UK, EU and WHO short-term ambient guideline values. Most exceedances of AEGL or ERPG guideline values were at levels likely only to cause discomfort to exposed populations (hydrogen cyanide, hydrogen chloride, hydrogen fluoride and formaldehyde), though for several substances the exceedances could have potentially given rise to more serious health effects (acrolein, phosphine, phosgene and methyl isocyanate). In the latter cases, the observed high concentrations are likely to be due to cross-interference from other substances that absorb in the mid-range of the infrared spectrum, particularly when the ground level plume is very concentrated.
Topics: Acrolein; Air Pollutants; Benzene; Environmental Monitoring; Fires; Formaldehyde; Humans; Hydrochloric Acid; Hydrogen; Phosgene
PubMed: 35231840
DOI: 10.1016/j.envint.2022.107152 -
The Journal of Physical Chemistry. B Nov 2021The wide range of applications of the isocyanates across multiple industries sparks the interest in the study of their phase behavior. A molecular simulation is a...
The wide range of applications of the isocyanates across multiple industries sparks the interest in the study of their phase behavior. A molecular simulation is a powerful tool that can go beyond experimental investigations relying on a molecular structure of a chemical. The success of a molecular simulation relies on a description of the system, namely, force field, and its parameterization on reproducing properties of interest. In this work, we propose a united-atom force field based on the transferable potentials for phase equilibria (TraPPE) to model the vapor-liquid phase behavior of isocyanates. With Monte Carlo and molecular dynamics simulation methods and the introduced force field, we modeled vapor-liquid equilibrium for a family of linear mono-isocyanates, from methyl isocyanate to hexyl isocyanate, and hexamethylene diisocyanate. Additionally, we performed similar calculations for methyl, ethyl, and butyl isocyanates based on the all-atom GAFF-IC force field available in the literature for modeling isocyanate viscosities. We showed that the developed TraPPE-based force field generally overperformed the GAFF-IC force field and overall showed excellent performance in modeling phase behavior of isocyanates. Based on the simulated vapor pressures for the considered compounds, we estimated the Antoine equation parameters to calculate the vapor pressure in a range of temperatures. The predictions are of particular use in the investigation of thermodynamic properties for those isocyanates lacking experimental vapor pressure data. Results can also be employed in modeling the phase behavior of isocyanate mixtures to investigate their sensing and capturing. Furthermore, from the vapor-liquid equilibrium binodals, we predicted the critical properties of isocyanates which can be used in thermodynamic models based on an equation of state.
Topics: Gases; Isocyanates; Molecular Dynamics Simulation; Monte Carlo Method; Thermodynamics
PubMed: 34735160
DOI: 10.1021/acs.jpcb.1c07132