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Environmental Health Perspectives Feb 2015The U.S. EPA's Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011. (Review)
Review
BACKGROUND
The U.S. EPA's Integrated Risk Information System (IRIS) completed an updated toxicological review of dichloromethane in November 2011.
OBJECTIVES
In this commentary we summarize key results and issues of this review, including exposure sources, identification of potential health effects, and updated physiologically based pharmacokinetic (PBPK) modeling.
METHODS
We performed a comprehensive review of primary research studies and evaluation of PBPK models.
DISCUSSION
Hepatotoxicity was observed in oral and inhalation exposure studies in several studies in animals; neurological effects were also identified as a potential area of concern. Dichloromethane was classified as likely to be carcinogenic in humans based primarily on evidence of carcinogenicity at two sites (liver and lung) in male and female B6C3F1 mice (inhalation exposure) and at one site (liver) in male B6C3F1 mice (drinking-water exposure). Recent epidemiologic studies of dichloromethane (seven studies of hematopoietic cancers published since 2000) provide additional data raising concerns about associations with non-Hodgkin lymphoma and multiple myeloma. Although there are gaps in the database for dichloromethane genotoxicity (i.e., DNA adduct formation and gene mutations in target tissues in vivo), the positive DNA damage assays correlated with tissue and/or species availability of functional glutathione S-transferase (GST) metabolic activity, the key activation pathway for dichloromethane-induced cancer. Innovations in the IRIS assessment include estimation of cancer risk specifically for a presumed sensitive genotype (GST-theta-1+/+), and PBPK modeling accounting for human physiological distributions based on the expected distribution for all individuals 6 months to 80 years of age.
CONCLUSION
The 2011 IRIS assessment of dichloromethane provides insights into the toxicity of a commonly used solvent.
Topics: Carcinogens, Environmental; Environmental Pollutants; Humans; Lung Neoplasms; Methylene Chloride; Models, Theoretical; Mutagenicity Tests; Neoplasms; Risk Assessment; United States; United States Environmental Protection Agency
PubMed: 25325283
DOI: 10.1289/ehp.1308030 -
International Journal of Molecular... Jul 2020Microglial hyperactivation and neuroinflammation are known to induce neuronal death, which is one of the main causes of neurodegenerative disorders. We previously found...
Microglial hyperactivation and neuroinflammation are known to induce neuronal death, which is one of the main causes of neurodegenerative disorders. We previously found that Aquilariae Lignum extract attenuated both neuronal excitotoxicity and neuroinflammation in vivo and in vitro. For further analysis, we extracted the methylene chloride fraction of Aquilariae Lignum to determine the bioactive compounds. In this study, we investigated the anti-neuroinflammatory effects and underlying mechanisms of the Aquilariae Lignum fraction (ALF) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 cells were pretreated with ALF (0.5, 1, and 2.5 μg/mL) before treatment with LPS (1 μg/mL). Pretreatment with ALF significantly attenuated the LPS-induced overproductions of nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E (PGE), and interleukin (IL)-1β. These anti-inflammatory effects were supported by ALF-mediated modulation of the nuclear factor-kappa B (NF-κB) pathway. Furthermore, ALF exerted strong anti-inflammasome effects, as shown by IL-1β-specific inhibitory activity, but not activity against tumor necrosis factor (TNF)-α, along with inhibition of caspase-1 activity and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3)-related molecules. These results indicate the potent anti-neuroinflammatory activity of ALF and that its underlying mechanism may involve the regulation of NLRP3 inflammasome-derived neuroinflammation in microglial cells.
Topics: Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Dinoprostone; Gene Expression Regulation; Heme Oxygenase-1; Humans; Inflammation; Interleukin-1beta; Lipopolysaccharides; Methylene Chloride; Microglia; NF-kappa B; Nitric Oxide; Signal Transduction; Thymelaeaceae; Tumor Necrosis Factor-alpha
PubMed: 32751738
DOI: 10.3390/ijms21155465 -
European Journal of Epidemiology Mar 2020Studies of occupational solvent exposures and amyotrophic lateral sclerosis (ALS) have been conflicting. We conducted a population-based case-control study of mixed...
Studies of occupational solvent exposures and amyotrophic lateral sclerosis (ALS) have been conflicting. We conducted a population-based case-control study of mixed occupational solvent exposures and ALS. Using the Danish National Patient Registry, we identified ALS cases in Denmark from 1982 to 2013, and matched them to 100 controls based on sex and birth year. We estimated cumulative exposures to solvents (benzene, methylene chloride, toluene, trichloroethylene, perchloroethylene, and 1,1,1-trichloroethane) via job exposure matrices and applied them to occupational history from the Danish Pension Fund. Sex-stratified conditional logistic regression analyses revealed higher adjusted odds of ALS for men with exposure to benzene (aOR = 1.20; 95% CI 1.02, 1.41) and methylene chloride (aOR = 1.23; 95% CI 1.07, 1.42). We used weighted quantile sum regression to explore combined solvent exposures and risk of ALS in exposed subjects and found increased odds of 26 to 28% in all exposure lag periods for every one-unit increase in the mixture index in men. Weights of methylene chloride predominated the mixture index in all lag periods. Our study suggests an increased risk of ALS in men exposed to multiple solvents, with the greatest influence being from methylene chloride. These findings highlight the need to utilize mixtures analysis when considering co-occurring exposures.
Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Case-Control Studies; Denmark; Female; Humans; Male; Methylene Chloride; Middle Aged; Occupational Diseases; Occupational Exposure; Population Surveillance; Risk Factors; Solvents
PubMed: 32193761
DOI: 10.1007/s10654-020-00624-5 -
Environment International Sep 2019Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these...
INTRODUCTION
Potentially carcinogenic hazardous air pollutants (air toxics) have been inconsistently associated with breast cancer. Whether metabolic factors modify these associations is unknown. We studied 29 non-metallic air toxics classified as mammary gland carcinogens in animal studies in relation to breast cancer risk.
METHODS
Participants included 49,718 women from the Sister Study. Census tract air toxic concentration estimates from the 2005 National Air Toxics Assessment were linked to enrollment residential addresses. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for individual air toxics were estimated using Cox regression. Body mass index (BMI) was considered a potential modifier. Relevant mixtures were identified using classification trees.
RESULTS
Over follow-up (average = 8.4 years), 2975 women were newly diagnosed with breast cancer (invasive or ductal carcinoma in situ). Several air toxics, including methylene chloride, polycyclic organic matter, propylene dichloride, and styrene, were associated with increased risk. Of these, methylene chloride was most consistently associated with risk across multiple analyses. It was associated with overall (HR = 1.21 (95%CI = 1.07-1.38)) and estrogen receptor positive (ER+) invasive breast cancer (HR = 1.28 (95%CI = 1.08-1.52)) in individual pollutant models, although no dose-response was observed. Associations were stronger among overweight/obese (vs. non-overweight/obese) women (p < 0.05) for six air toxics. The classification tree identified combinations of age, methylene chloride, BMI, and four other toxics (propylene dichloride, ethylene dibromide, ethylidene dichloride, styrene) related to overall breast cancer.
CONCLUSIONS
Some non-metallic air toxics, particularly methylene chloride, were associated with the hazard for overall and ER+ breast cancer. Overweight/obese women may be particularly susceptible to air toxics.
Topics: Air Pollutants; Air Pollution; Breast Neoplasms; Carcinogens; Cohort Studies; Female; Humans
PubMed: 31226564
DOI: 10.1016/j.envint.2019.06.007 -
Global Change Biology Apr 2022Anthropogenic activities and natural processes release dichloromethane (DCM, methylene chloride), a toxic chemical with substantial ozone-depleting capacity. Specialized...
Anthropogenic activities and natural processes release dichloromethane (DCM, methylene chloride), a toxic chemical with substantial ozone-depleting capacity. Specialized anaerobic bacteria metabolize DCM; however, the genetic basis for this process has remained elusive. Comparative genomics of the three known anaerobic DCM-degrading bacterial species revealed a homologous gene cluster, designated the methylene chloride catabolism (mec) gene cassette, comprising 8-10 genes encoding proteins with 79.6%-99.7% amino acid identities. Functional annotation identified genes encoding a corrinoid-dependent methyltransferase system, and shotgun proteomics applied to two DCM-catabolizing cultures revealed high expression of proteins encoded on the mec gene cluster during anaerobic growth with DCM. In a DCM-contaminated groundwater plume, the abundance of mec genes strongly correlated with DCM concentrations (R = 0.71-0.85) indicating their potential value as process-specific bioremediation biomarkers. mec gene clusters were identified in metagenomes representing peat bogs, the deep subsurface, and marine ecosystems including oxygen minimum zones (OMZs), suggesting a capacity for DCM degradation in diverse habitats. The broad distribution of anaerobic DCM catabolic potential infers a role for DCM as an energy source in various environmental systems, and implies that the global DCM flux (i.e., the rate of formation minus the rate of consumption) might be greater than emission measurements suggest.
Topics: Anaerobiosis; Biodegradation, Environmental; Ecosystem; Groundwater; Methylene Chloride
PubMed: 34967079
DOI: 10.1111/gcb.16068 -
Journal of Pharmacy & Bioallied Sciences Nov 2021The aim of the study is to investigate the effect of joint surface preparations and chemical surface treatment given to prepared surface on the transverse strength of...
AIM
The aim of the study is to investigate the effect of joint surface preparations and chemical surface treatment given to prepared surface on the transverse strength of repaired denture base resin.
METHODOLOGY
Two hundred and twenty specimens (DPI India) were randomly allocated into eight groups ( = 10), according to the combination of joint surface preparation (Butt joint, 45° bevel, and rounded joint) and chemical surface treatment (methylene chloride, ethyl acetate, and methyl methacrylate) for 30 and 60 s each. Specimens, after surface treatment, were repaired with self-cured resin (DPI India) and then subjected to 3-point bending test to measure transverse strength. Fractured surfaces were viewed under stereomicroscope and subjected to AutoCAD analysis to determine type of failure (adhesive or cohesive) and measure their area. Measurement data were analyzed by one-way analysis of variance, paired -test, Dunnett's D test, and multiple comparison Bonferroni -test, with a 5% significance level.
RESULTS
Most of the comparisons between the test specimens were statistically significant. Specimens (methylene chloride for 60 s and rounded joint) show 60%-70% gain of strength.
CONCLUSIONS
For providing better bond strength to a repaired specimen, the segment of fractured specimens to be provided "Rounded joint" preparation with etching by methylene chloride for 60 s.
PubMed: 35017918
DOI: 10.4103/jpbs.jpbs_217_21 -
Phytochemical investigations and biological work on aerial parts and roots of Trigonella polycerata.Pakistan Journal of Pharmaceutical... Jul 2022The purpose of this study was to purify the phytoconstituents and to explore the antibacterial, antifungal, phytotoxic and cytotoxic potential of dichloromethane and...
The purpose of this study was to purify the phytoconstituents and to explore the antibacterial, antifungal, phytotoxic and cytotoxic potential of dichloromethane and methanol extracts of aerial and root parts of Trigonella polycerata. The phytochemical study on methanol extract of aerial parts of the plant led to the isolation and purification of seven compounds that were identified as 3,4-dimethoxycinnamaldehyde, Trigocoumarin, 6,7,8-trimethoxycoumarin, Penduletin, 5-hydroxy-3,6,7,4´-tetramethoxyflavone, 3,5,7-trihydroxy-6,4-dimethoxyflavone and 5-hydroxy-4,7-dimethoxyflavone. These structures were elucidated by interpretation of EI-MS and NMR spectral data. The plant aerial parts methanol extract (TPAM) demonstrated higher antibacterial (78.99%), phytotoxic (85% growth regulation at 1000μg/mL) and cytotoxic activities (LD: 45.643μg/mL). While the methanol root extract (TPRM) was highly active against bacteria's; Salmonella typhi (71.56%), Staphylococcus aureus (70.15%), Escherichia coli (69%), fungi like Candida albicans (70.21%) and moderately active against Brine shrimp larvae (LD: 125.663μg/mL). The dichloromethane aerial (TPAD) and root (TPRD) extracts exhibited significant antibacterial (78.03% and 50.21% inhibitions respectively) and phytotoxic (55% growth regulation at 1000μg/mL) potential. Only TPAD indicated the best inhibition against fungi; Aspergillus flavus (75.31%) and moderate inhibition against Microsporum canis (42.21%). This phytochemical and biological work is the first time reported in Trigonella polycerata.
Topics: Anti-Bacterial Agents; Antifungal Agents; Methanol; Methylene Chloride; Microbial Sensitivity Tests; Phytochemicals; Plant Components, Aerial; Plant Extracts; Trigonella
PubMed: 36218105
DOI: No ID Found -
Molecules (Basel, Switzerland) Sep 2022Lam (syn. .) leaves are globally acclaimed for their nutritional content and mitigation of malnutrition. In most impoverished rural communities including Limpopo,...
Lam (syn. .) leaves are globally acclaimed for their nutritional content and mitigation of malnutrition. In most impoverished rural communities including Limpopo, Mpumalanga and KwaZulu Natal of South Africa, powdered leaves of are applied as a nutritional supplement for readily available food such as porridge for malnourished children and even breast-feeding mothers. Widely practiced and admired is also the use of the plant seed in the do-it-yourself purification of water by rural South Africans. This study aimed at identifying the chemical and nutritional marker compounds present in South African seed oils using high resolution 1-2-dimension gas chromatography in order to give scientific validation to its uses in cosmetics and particularly in culinary practices. Results obtained from two-dimension tandem mass spectrometry chemical signature revealed over 250 compounds, five times more than those reported from one-dimension gas chromatography. Whereas previous reports from gas chromatography-mass spectrometry analysis reported oleic acid (70-78%) as the major compound from oil samples from other countries, seed oil from South Africa is marked by 13-octadeaconic acid with 78.62% and 41.9% as the predominant monounsaturated fatty acid in the hexane and dichloromethane extracts respectively. This was followed by vaccenic acid, an isomer of oleic acid at 51% in the acetone extract, 9-octadecanoic acid-(z)-methyl ester at 39.18%, 21.34% and 10.06% in dichloromethane, hexane and acetone extracts respectively. However, a principal component analysis with R = 0.98 of the two-dimension tandem mass spectrometry cum chemometric analysis indicated n-hexadecanoic acid, oleic acid, 9-octadecanoic acid-(z)-methyl ester and -vaccenic acid with a probability of 0.96, 0.88, 0.80 and 0.79 respectively as the marker compounds that should be used for the quality control of seed oils from South Africa. This study demonstrates that South African oils contain C-18 monounsaturated fatty acids similar to oils from Egypt (76.2%), Thailand (71.6%) and Pakistan (78.5%) just to mention but a few. These fatty acids are sunflower and olive oil type-compounds and therefore place seed oil for consideration as a cooking oil amongst its other uses.
Topics: Acetone; Child; Esters; Fatty Acids; Gas Chromatography-Mass Spectrometry; Hexanes; Humans; Methylene Chloride; Moringa; Moringa oleifera; Oleic Acid; Olive Oil; Palmitic Acid; Plant Extracts; Plant Oils; Seeds; South Africa; Stearic Acids; Water
PubMed: 36144484
DOI: 10.3390/molecules27185749 -
Journal of Ethnopharmacology Jan 2023Streptococcus mutans a key pathogen, produces biofilm, acids and extracellular polysaccharides in the oral cavity; which leads to the development of dental caries....
ETHNOPHARMACOLOGICAL RELEVANCE
Streptococcus mutans a key pathogen, produces biofilm, acids and extracellular polysaccharides in the oral cavity; which leads to the development of dental caries. Control of these pathogenic markers can prevent dental caries. Uvaria chamae P. Beauv. is a medicinal plant traditionally used for many ailments including oral infections. Root, leaves and bark extracts has proven antibacterial activity including activity against caries causing S. mutans. However, its effect on the virulence properties of S. mutans, responsible for the development of dental caries, has not been studied.
AIM OF THE STUDY
This study investigated the phytochemical constituents, anti-S. mutans, anti-adherence and anti-acidogenic activity of U. chamae root extract.
MATERIALS AND METHODS
Extracts were prepared and phytochemical analysis was performed. Minimum inhibitory concentrations (MIC) were determined, and MIC and sub-MIC concentrations of the best solvent were selected for their effect on the virulence factors of S. mutans. The results were analysed using one-way ANOVA and Wilcoxon Rank Sum Tests.
RESULTS
The dichloromethane extract, with proanthocyanidin as a major chemical constituent, produced an MIC of 0.02 mg/ml. At 6 h, exposure to 0.005, 0.01, and 0.02 mg/ml extract significantly reduced S. mutans adherence by 39, 59, and 77% respectively (p < 0.05). Uvaria chamae also significantly inhibited acid production in S. mutans at 10, 12, 14 and 16 h (p < 0.05). At ½ MIC, the plant extract caused remarkable downregulation of the virulence genes responsible for the adherence, biofilm formation, extracellular polysaccharide synthesis and acid production.
CONCLUSIONS
This suggests that U. chamae extract may potentially be used to inhibit the proliferation of S. mutans and silencing the expression of pathology-related genes, which will prevent the development of dental caries.
Topics: Acids; Anti-Bacterial Agents; Biofilms; Dental Caries; Methylene Chloride; Microbial Sensitivity Tests; Phytochemicals; Plant Extracts; Proanthocyanidins; Solvents; Streptococcus mutans; Uvaria; Virulence Factors
PubMed: 36096348
DOI: 10.1016/j.jep.2022.115673 -
Environmental Research Oct 2022Many volatile organic compounds (VOCs) are used for experiments at universities, and most of them contain benzene, toluene, ethylbenzene, xylene, and an extraction...
Many volatile organic compounds (VOCs) are used for experiments at universities, and most of them contain benzene, toluene, ethylbenzene, xylene, and an extraction solvent of dichloromethane. This study aimed to investigate the indoor concentrations of these five compounds in different locations on campus and to evaluate possible health risks for faculty members and students in a medical university. We selected 10 locations as sampling sites to conduct 4-h monitoring sessions on weekdays each season during 2019-2020. We used a 6-liter canister to collect air samples and analyzed these five VOCs via gas chromatography with a flame ionization detector. Monte Carlo simulation was performed to evaluate the carcinogenic and noncarcinogenic risks of these five VOCs. We found that dichloromethane was the most highly detected compound (median: 621.07 μg/m; range: 44.01-8523.91 μg/m), and the Department of Medicine had the highest concentration of the total of these VOCs among all of the locations (median: 5595.29 μg/m; range: 1565.67-7398.66 μg/m). The median carcinogenic risks of dichloromethane and benzene were 6.36 × 10 (95% confidence interval [CI]: 6.83 × 10-7.37 × 10) and 5.47 × 10 (95% CI: 4.03 × 10-2.42 × 10), respectively, for faculty members, and the lower risks of 3.14 × 10 (95% CI: 3.39 × 10-3.64 × 10) and 2.69 × 10 (95% CI: 1.97 × 10-1.19 × 10) were estimated for the students. The chronic noncarcinogenic risks of four VOCs were less than one, except for dichloromethane with a median hazard index of 1.92 (95% CI: 2.11 × 10-2.22 × 10). This study observed the spatial variation in the concentrations of the total of five VOCs and dichloromethane. The carcinogenic risks were classified as being at the possible level, and the noncarcinogenic risk of dichloromethane was greater than the acceptable level. Increasing local exhaust ventilation during the experiment and reducing the using amount of dichloromethane are recommended actions to reduce VOCs exposures in the medical university.
Topics: Air Pollutants; Benzene; Environmental Monitoring; Humans; Methylene Chloride; Risk Assessment; Universities; Volatile Organic Compounds
PubMed: 35697085
DOI: 10.1016/j.envres.2022.113644