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New Solutions : a Journal of... Nov 2023Last May 2023, the U.S. Environmental Protection Agency (EPA) published a proposed rule to restrict the production and use of a dangerous chemical called methylene...
Last May 2023, the U.S. Environmental Protection Agency (EPA) published a proposed rule to restrict the production and use of a dangerous chemical called methylene chloride pursuant to its authority under the Toxic Substance Control Act-the first such measure since Congress significantly overhauled that law in 2016. Methylene chloride presents a variety of health and safety risks, particularly for workers in industries in which the chemical is still widely used. In support of the proposed rule, the EPA prepared a document called a cost-benefit analysis, which purports to evaluate the rule by calculating its net benefits-that is, the rule's likely benefits over and above its likely costs. Cost-benefit analysis has been the subject of substantial criticism in recent decades, and the Biden administration is pursuing significant reforms for how these analyses are performed. Together with my colleague Dr. Federico Holm, I submitted comments to the EPA criticizing the cost-benefit analysis for the proposed methylene chloride rule. In these comments, we criticize the agency for continuing to employ an overly formalistic approach to cost-benefit analysis, which both systematically undervalues the benefits of regulations and ignores impact issues like worker justice. We also criticize several specific aspects of the agency's analytical methodology, including its failure to follow the proposed reforms now being developed by the Biden administration.
Topics: Humans; United States; Methylene Chloride; United States Environmental Protection Agency
PubMed: 37644913
DOI: 10.1177/10482911231198148 -
Chemical Senses Jan 2024Although studies have shown that olfaction may contribute to the perception of tastant, literature is scarce or circumstantial, especially in humans. This study aims to...
Although studies have shown that olfaction may contribute to the perception of tastant, literature is scarce or circumstantial, especially in humans. This study aims to (i) explore whether humans can perceive solutions of basic prototypical tastants through orthonasal and retronasal olfaction and (ii) to examine what volatile odor compounds (VOCs) underlie this ability. Solutions of 5 basic tastants (sucrose, sodium chloride, citric acid, monosodium glutamate [MSG], quinine) dissolved in water, and 2 fatty acids (oleic and linoleic acid) dissolved in mineral oil were prepared. Triangle discrimination tests were performed (n = 41 in duplicate) to assess whether the tastant solutions can be distinguished from blanks (solvents) through ortho- and retronasal olfaction. Participants were able to distinguish all tastant solutions from blank through orthonasal olfaction. Only sucrose, sodium chloride, oleic acid, and linoleic acid were distinguished from blank by retronasal olfaction. Ethyl dichloroacetate, methylene chloride, and/or acetone were identified in the headspace of sucrose, MSG, and quinine solutions but not in the headspace of water, sodium chloride, and citric acid solutions. Fat oxidation compounds such as alcohols and aldehydes were detected in the headspace of the oleic and linoleic acid solutions but not the mineral oil. We conclude that prototypical tastant solutions can be discriminated from water and fatty acid solutions from mineral oil through orthonasal olfaction. Differences in the volatile headspace composition between blanks and tastant solutions may have facilitated the olfactory discrimination. These findings can have methodological implications for future studies assessing gustatory perception using these prototypical taste compounds.
Topics: Humans; Smell; Sodium Chloride; Sodium Glutamate; Quinine; Mineral Oil; Taste; Water; Sucrose; Citric Acid; Linoleic Acids
PubMed: 38175732
DOI: 10.1093/chemse/bjad054 -
Natural Product Research Jul 2020Genus (Fabaceae) comprises several species, which are widely distributed in tropical and subtropical regions of the world. The plants of this genus exhibited... (Review)
Review
Genus (Fabaceae) comprises several species, which are widely distributed in tropical and subtropical regions of the world. The plants of this genus exhibited significant role in traditional medicine targeting different diseases. Alkaloids and flavonoids were reported as the chief bioactive constituents of this genus with a wide range of biological activities. About 143 alkaloids were isolated from sp. Anticonvulsant, anxiolytic, curare-like activity, insecticidal and cytotoxic activities were reported for sp. alkaloids. The present work is an overview of the isolated alkaloids from sp. with their reported biological activities.[Figure: see text] CHCl3: Chloroform; CNS: Central nervous system; DCM: Methylene chloride; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; ; ERα/β: Estrogen receptors α/β; EtOAc: Ethyl acetate; EtOH: Ethanol; Hep-G2: Human liver carcinoma cell lines; HIV: Human immunodeficiency virus; HL-60: Human promyelocytic leukemia cells; K-562: Human immortalized myelogenous leukemia cell line; LPS: Lipopolysaccharide; MeOH: Methanol; MOLT-4: Acute lymphoblastic leukemia cell line; nAChRs: nicotinic acetylcholine receptors; NO: Nitric oxide; NREM: non-rapid eye movement; Pet. ether: Petroleum ether; RBA: Receptor binder affinity; TRAIL: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand.
Topics: Alkaloids; Cell Line, Tumor; Erythrina; Estrogen Receptor alpha; Fabaceae; Humans
PubMed: 31226894
DOI: 10.1080/14786419.2018.1564300 -
Drug Discoveries & Therapeutics Jul 2023The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations.... (Review)
Review
The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.
Topics: Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Lactic Acid; Microspheres; Polyesters; Solvents; Particle Size
PubMed: 37245983
DOI: 10.5582/ddt.2023.01008 -
JAMA Internal Medicine Jun 2021Methylene chloride is a halogenated organic solvent widely used in paint strippers, cleaners, adhesives, and sealants. Despite label warnings and occupational standards,...
IMPORTANCE
Methylene chloride is a halogenated organic solvent widely used in paint strippers, cleaners, adhesives, and sealants. Despite label warnings and occupational standards, methylene chloride-related fatalities continue to occur in the United States.
OBJECTIVE
To identify and analyze methylene chloride-related fatalities in the US.
DESIGN, SETTING, AND PARTICIPANTS
For this case series, we conducted systematic searches of sources, including PubMed and government databases, for unintentional fatalities in the US that were associated with exposure to methylene chloride or products containing methylene chloride between 1980 and 2018. We reviewed all available information, including inspection reports, autopsy reports, and medical records; data analyses were conducted from August 2018 to August 2020. Cases were categorized as those occurring in the home (consumer deaths) or at work (occupational deaths).
EXPOSURES
Methylene chloride or products containing methylene chloride.
MAIN OUTCOMES AND MEASURES
To determine characteristics of the methylene chloride-related fatalities, we recorded demographic information; the setting; circumstances, including information on safety measures used, if available; and products used. Where medical records were available, we recorded toxicology results and autopsy findings. We also obtained data about nonfatal methylene chloride cases from the American Association of Poison Control Centers.
RESULTS
From 1980 to 2018, 85 methylene chloride-related fatalities were identified in the US, including 74 (87%) in occupational settings; of those who died, 75 (94%) were men, and for the 70 cases with available information, the median (interquartile range) age of the decedents was 31 (24-46) years. Paint strippers were the most common products involved in methylene chloride-related fatalities (n = 60). The proportion of occupational fatalities related to paint stripping increased from 22 (55%) before 2000 to 30 (88%) after 2000. Similarly, occupational fatalities associated with bathtub or paint stripping in bathrooms increased from 2 (5%) before 2000 to 21 (62%) after 2000. From 1985 to 2017, the American Association of Poison Control Centers documented 37 201 nonfatal methylene chloride cases, with a decrease in the annual number of cases starting in the late 1990s.
CONCLUSIONS AND RELEVANCE
Results of this case series demonstrated that despite regulations to address the toxic effects of methylene chloride use for consumers and workers, there are continuing fatalities in the US, particularly in occupational settings. Prevention of fatalities associated with methylene chloride exposure should emphasize the use of safer substitutes, rather than hazard warnings or reliance on personal protective equipment.
Topics: Adult; Female; Humans; Male; Methylene Chloride; Middle Aged; Occupational Exposure; Poison Control Centers; Poisoning; United States; Young Adult
PubMed: 33871539
DOI: 10.1001/jamainternmed.2021.1063 -
Photodermatology, Photoimmunology &... Jul 2022Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light....
BACKGROUND
Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light. Photodynamic therapy has been described recently as a promising strategy for treatment of leishmaniasis. This study aims to evaluate the in vitro phototoxic, morphological, and apoptotic effect of methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy on the viability of Leishmania tropica promastigotes.
METHODS
Parasites were treated with methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a or/and methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy, and cell proliferation, morphological changes, and apoptosis were evaluated by XTT, giemsa staining, DAPI staining, and DNA fragmentation, respectively.
RESULTS
Parasite viability was significantly different in between the groups treated with methylene blue, toluidine blue, and pheophorbide a, with or without irradiation. chloro-aluminum phthalocyanine treatment did not lead to any alterations in cell viability in Leishmania tropica promastigotes with or without irradiation. DAPI staining results indicated that apoptotic bodies and nucleus fragmentation started to be visible in methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy groups. DNA ladder pattern which is used to define apoptosis was observed in irradiated methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a groups.
CONCLUSIONS
The results revealed that apoptosis-induced cell death was observed in Leishmania tropica promastigotes after the application of photosensitizers in combination with light irradiation.
Topics: Humans; Leishmania tropica; Methylene Blue; Photochemotherapy; Photosensitizing Agents; Tolonium Chloride
PubMed: 34897808
DOI: 10.1111/phpp.12758 -
Fitoterapia Jun 2023Chagas disease, African trypanosomiasis and Leishmaniasis are neglected parasitic diseases which affect millions of people worldwide. In a previous work, we report the...
Chagas disease, African trypanosomiasis and Leishmaniasis are neglected parasitic diseases which affect millions of people worldwide. In a previous work, we report the antiprotozoal activity of the dichloromethane extract of Mikania periplocifolia Hook. & Arn. (Asteraceae). The aim of this work was to isolate and identify the bioactive compounds present in the extract. The fractionation of the dichloromethane extract has led to the isolation of the sesquiterpene lactone miscandenin and the flavonoid onopordin, together with the sesquiterpene lactones mikanolide, dihydromikanolide and deoxymikanolide, which have previously shown antiprotozoal activity. Miscandenin and onopordin were assayed in vitro against Trypanosoma cruzi, T. brucei and Leishmania braziliensis. Miscandenin was active against T. cruzi trypomastigotes and amastigotes with IC values of 9.1 and 7.7 μg/ml, respectively. This sesquiterpene lactone and the flavonoid onopordin showed activity against T. brucei trypomastigotes (IC = 0.16 and 0.37 μg/ml) and L. braziliensis promastigotes (IC = 0.6 and 1.2 μg/ml), respectively. The CC values on mammalian cells were 37.9 and 53.4 μg/ml for miscandenin and onopordin, respectively. Besides, the pharmacokinetic and physicochemical properties of miscandenin were assessed in silico, showing a good drug-likeness profile. Our results highlight this compound as a promising candidate for further preclinical studies in the search of new drugs for the treatment of trypanosomiasis and leishmaniasis.
Topics: Animals; Humans; Asteraceae; Mikania; Methylene Chloride; Plant Extracts; Molecular Structure; Antiprotozoal Agents; Trypanosoma cruzi; Leishmaniasis; Flavonoids; Lactones; Sesquiterpenes; Mammals
PubMed: 37019368
DOI: 10.1016/j.fitote.2023.105499 -
The Science of the Total Environment Jun 2024Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We... (Meta-Analysis)
Meta-Analysis Review
Parkinson's disease (PD) is a neurodegenerative disorder and leading cause of death worldwide, whose pathogenesis has been linked to toxic environmental exposures. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (i) to compile, and group by exposure setting (non-specified general; residential; occupational), environmental factors reported to modulate the risk of developing PD and (ii) to map and geospatially analyze global regions of both research activity and paucity. Among the broader environmental settings, occupational exposures had the highest average odds ratio value at 3.82, followed by general (non-specified or mixed) exposures at 3.07, and residential exposures at 2.36. Occupational exposure to industrial toxins was the highest ranked subset of exposures with an odds ratio of 10.74. Among the studies meeting the inclusion criteria, 75 % were conducted in Europe or the Western United States. The number of individuals partaking per study ranged from a high of 55,585 (Taiwan) to a low of 233 (Faroe Islands), with a mean of n = 14,462. The top three environmental factors associated with high odds ratios for increased risk of developing PD were (i) exposure to dyes (25.33), (ii) methylene chloride (16.5) and specifically in adult men (iii) consumption of fatty whale meat (10.57), which is known to harbor a broad spectrum of so called persistent, bioaccumulative, toxic (PBT) pollutants. Geospatially, the highest odds ratio values were identified in European countries, whereas notable data gaps were revealed for South America, Australia, Africa, and the majority of Asia with the exception of Taiwan. Whereas occupational exposures to industrial chemicals, such as harmful dyes and methylene chloride, ranked highest in risk values, available data suggest notable opportunities for reducing PD cases globally by limiting harmful environmental exposures to a spectrum of toxic chemicals, particularly via the food intake route. Thus, current efforts in improving environmental quality globally by limiting toxic emission may deliver the added benefit of helping to reign in PD. Agents of concern in this respect include pesticides (e.g., paraquat, demeton, monocrotophos), particulate matter associated with air pollution, and a spectrum of organic and inorganic neurotoxins including heavy metals.
Topics: Parkinson Disease; Humans; Environmental Exposure; Environmental Pollutants; Risk Factors; Occupational Exposure
PubMed: 38685425
DOI: 10.1016/j.scitotenv.2024.172838