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RSC Advances Oct 2019Herein we describe a metal free and one-pot pathway for the synthesis of industrially important cyclic carbonates such as ethylene carbonate (EC) and propylene...
Herein we describe a metal free and one-pot pathway for the synthesis of industrially important cyclic carbonates such as ethylene carbonate (EC) and propylene carbonates (PC) from molecular CO under mild reaction conditions. In the actual synthesis, the alkylene halohydrins such as alkylene chloro- or bromo or iodohydrin and organic superbase, 1,8-diazabicyclo-[5.4.0]-undec-7-ene (DBU) reacted equivalently with CO at room temperature. The syntheses of cyclic carbonates were performed in DMSO as a solvent. Both 1,2 and 1,3 halohydrin precursors were converted into cyclic carbonates except 2-bromo- and iodoethanol, which were reacted equivalently with DBU through -alkylation and formed corresponding -alkylated DBU salts instead of forming cyclic carbonates. NMR analysis was used to identify the reaction components in the reaction mixture whereas this technique was also helpful in terms of understanding the reaction mechanism of cyclic carbonate formation. The mechanistic study based on the NMR analysis studies confirmed that prior to the formation of cyclic carbonate, a switchable ionic liquid (SIL) formed from alkylene chlorohydrin, DBU and CO. As a representative study, the synthesis of cyclic carbonates from 1,2 chlorohydrins was demonstrated where the synthesis was carried out using chlorohydrin as a solvent as well as a reagent. In this case, alkylene chlorohydrin as a solvent not only replaced DMSO in the synthesis but also facilitated an efficient separation of the reaction components from the reaction mixture. The EC or PC, [DBUH][Cl] as well as an excess of the alkylene chlorhydrin were separated from each other following solvent extraction and distillation approaches. In this process, with the applied reaction conditions, >90% yields of EC and PC were achieved. Meanwhile, DBU was recovered from formed [DBUH][Cl] by using NaCl saturated alkaline solution. Most importantly here, we developed a metal free, industrially feasible CO capture and utilization approach to obtain EC and PC under mild reaction conditions.
PubMed: 35540956
DOI: 10.1039/c9ra06765e -
Occupational and Environmental Medicine Aug 1997A previous study reported a fivefold increase in mortality from pancreatic cancer and a threefold increase in lymphopoietic and haematopoietic cancer among 278 men who...
OBJECTIVES
A previous study reported a fivefold increase in mortality from pancreatic cancer and a threefold increase in lymphopoietic and haematopoietic cancer among 278 men who were assigned to a now dismantled Union Carbide chlorohydrin unit in the Kanawha Valley of West Virginia. There were also significant trends with duration of employment. The purpose of this study was to determine whether a comparable increased risk in mortality from pancreatic cancer and lymphopoietic and haematopoietic cancer occurred among male employees assigned to the Dow Chemical Company's ethylene and propylene chlorohydrin production processes.
METHODS
The cohort consisted of 1361 male employees who worked at the company's Freeport, Texas, Plaquemine, Louisiana or Midland, Michigan plants. Subjects were considered to have had a minimum of 30 days of workplace experience in 1940-92, in the ethylene chlorohydrin and propylene chlorohydrin process areas. These process areas were located within the ethylene oxide and propylene oxide production plants. A total of 300 deaths was observed to 31 December 1992.
RESULTS
The standardised mortality ratio (SMR) for all malignant neoplasms was 94 (95% CI 74 to 118). There was one pancreatic cancer death compared with 4.0 expected (SMR 25, 95% CI 1 to 140). There were 10 lymphopoietic and haematopoietic cancer deaths compared with 7.7 expected (SMR 129, 95% CI 62 to 238). Additional analyses, which examined location, production process, duration of employment, and a 25 year induction latency period, were not significant.
CONCLUSIONS
The results provide some assurance that the Dow Chemical cohort, to date, has not experienced increased risks of pancreatic cancer and lymphopoietic and haematopoietic cancer as previously reported in a different cohort of chlorohydrin workers. Possible reasons are discussed for the inconsistent findings between the two cohorts.
Topics: Chlorohydrins; Cohort Studies; Confidence Intervals; Ethylene Chlorohydrin; Hematologic Neoplasms; Humans; Male; Occupational Diseases; Pancreatic Neoplasms
PubMed: 9326163
DOI: 10.1136/oem.54.8.592 -
Food and Chemical Toxicology : An... Oct 2022The detection of 2-chloroethanol in foods generally follows an assumption that the pesticide ethylene oxide has been used at some stage in the supply chain. In this... (Review)
Review
The detection of 2-chloroethanol in foods generally follows an assumption that the pesticide ethylene oxide has been used at some stage in the supply chain. In this situation the Pesticide Residues in Food Regulation (EC) 396/2005 requires 2-chloroethanol to be assessed as if equivalent to ethylene oxide, which has been classified as a genotoxic carcinogen. This review investigated whether this is an appropriate risk assessment approach for 2-chloroethanol. This involved an assessment of existing genotoxicity and carcinogenicity data, application of Structure Activity Based Read Across for carcinogenicity assessment, biological reactivity in the ToxTracker assay and micronuclei formation in HepaRG cells. Although we identified there is an absence of a standard oral bioassay for 2-chloroethanol, carcinogenicity weight-of-evidence assessment along with data on relevant structural analogues do not show evidence for carcinogenicity for 2-chloroethanol. The absence of genotoxicity was demonstrated for 2-chloroethanol and suitable analogues. In contrast, ethylene oxide showed reactivity towards markers indicative of direct DNA damage which is consistent with what is known about its mode-of-action. These data facilitate the understanding of 2-chloroethanol and given that it is not a genotoxic carcinogen suggest it must be assessed relative to non-cancer endpoints and a health protective Reference Dose should be established on that basis.
Topics: Carcinogenicity Tests; Carcinogens; DNA Damage; Ethylene Chlorohydrin; Ethylene Oxide; In Vitro Techniques; Mutagenicity Tests; Pesticide Residues; Structure-Activity Relationship
PubMed: 35863484
DOI: 10.1016/j.fct.2022.113290 -
Plant Physiology Jul 1934
PubMed: 16652903
DOI: 10.1104/pp.9.3.637 -
Journal of Occupational Health Jan 2020Occupational exposure to trichloroethylene (TCE) induces trichloroethylene hypersensitivity syndrome (TCEHS), which causes hypersensitivity dermatitis and hepatitis....
OBJECTIVES
Occupational exposure to trichloroethylene (TCE) induces trichloroethylene hypersensitivity syndrome (TCEHS), which causes hypersensitivity dermatitis and hepatitis. However, whether TCE itself or its two metabolites, trichloroethanol (TCEOH) and trichloroacetic acid (TCA), are involved in TCEHS remains unclear. Therefore, in this study we explored the allergens causing TCEHS and characterized TCEHS-related liver injury in guinea pigs.
METHOD
The guinea pig maximization test was performed using TCE, TCEOH, and TCA as candidate allergens. Skin inflammation was scored, and liver function and histopathological changes were evaluated by biochemical tests and hematoxylin and eosin staining, respectively.
RESULTS
The sensitization rates for TCE, TCEOH, and TCA were 90.0%, 50.0%, and 0.0%, respectively. In the TCE and TCEOH experimental groups, the skin showed varying degrees of erythema with eosinophil granulocyte infiltration in the dermis. Additionally, serum alanine aminotransferase and γ-glutamyl transpeptidase levels increased significantly, and histological analysis revealed focal hepatocellular necrosis with inflammatory cell infiltration in the liver.
CONCLUSIONS
TCE is the main cause of allergy and TCEOH is a secondary factor for allergy in guinea pigs. TCE and TCEOH can cause immune-mediated skin sensitization complicated by focal hepatic necrosis.
Topics: Animals; Chemical and Drug Induced Liver Injury; Ethylene Chlorohydrin; Female; Guinea Pigs; Hypersensitivity; Necrosis; Occupational Exposure; Skin Diseases; Trichloroacetic Acid; Trichloroethylene
PubMed: 32799435
DOI: 10.1002/1348-9585.12142 -
British Journal of Industrial Medicine Nov 1979Ethylene oxide, important as an intermediate product in the chemical industry and for sterilising hospital equipment, is mutagenic in several organisms; carcinogenicity...
Ethylene oxide, important as an intermediate product in the chemical industry and for sterilising hospital equipment, is mutagenic in several organisms; carcinogenicity has been suspected although this had not been supported by clinical data. Ethylene oxide has been produced by a Swedish company since the beginning of the 1940s. This paper describes a cohort study of the mortality and the cancer incidence among full-time exposed workers in ethylene oxide production, a group of maintenance workers with intermittent exposure and a group of unexposed controls. Investigation of the production processes in the building at different times has shown that workers were exposed to ethylene dichloride, ethylene chlorohydrin, ethylene, and small amounts of bis-(2-chloroethyl) ether as well as to ethylene oxide and traces of other chemicals. The full-time exposed cohort shows a considerable excess mortality deriving mainly from increased mortality from tumours and also from diseases of the circulatory system. The cancer incidence study, including living persons with malignancies, showed a significant excess in the full-time cohort. Of the 16 patients with tumours in the two more exposed cohorts there were three cases of leukaemia, six of tumours in the alimentary tract and four of urogenital malignancy. The excess mortality and cancer incidence cannot be attributed to any particular chemical in the production process, but ethylene oxide and ethylene dichloride are the prime suspects.
Topics: Chemical Industry; Environmental Exposure; Ethylene Chlorohydrin; Ethylene Dichlorides; Ethylene Oxide; Humans; Leukemia; Male; Mortality; Neoplasms; Occupational Diseases; Stomach Neoplasms; Sweden
PubMed: 508639
DOI: 10.1136/oem.36.4.276 -
National Toxicology Program Technical... Nov 1985Toxicology and carcinogenesis studies of 2-chloroethanol (99% pure), an industrial chemical and an intermediate in the synthesis of ethylene oxide, were conducted by...
Toxicology and carcinogenesis studies of 2-chloroethanol (99% pure), an industrial chemical and an intermediate in the synthesis of ethylene oxide, were conducted by dermal application of 2-chloroethanol dissolved in 70% ethanol:30% water (v/v) solutions to groups of 50 F344/N rats of each sex at doses of 0, 50, or 100 mg/kg for 103 weeks or to groups of 50 Swiss CD-1 mice of each sex at doses of 0, 7.5, or 15 mg per animal for 104 weeks (0, 253, or 630 mg/kg at week 1; 0, 180, 411 mg/kg at week 100). The control groups received skin applications of the vehicle; the mouse studies also included untreated control groups of 50 male and 50 females. 2-Chloroethanol solutions were applied to the clipped interscapular area of the animals once daily, 5 days per week for the test period. Rats received a volume of 0.18-0.22 ml of solution; mice received 0.10 ml of solution. In the 13-week studies, mortality was observed in male and female rats receiving 20 mg per day and higher. In the 104-week studies, the survival of high dose male mice was lower (P<0.05) than that of the vehicle controls (vehicle control, 26/50; 7.5 mg, 16/50; 15 mg, 12/50). Body weights of dosed mice were unaffected by 2-chloroethanol. The survival and body weight gain data suggest that the male and female rats and female mice could have tolerated a higher dose of 2-chloroethanol. Male mice probably could not have tolerated a higher dose than was applied to the skin. Seven high dose male mice died within 3 days of the start of dosing; all of these had inflammation at the site of dermal application. Five also had ulceration at the site of dermal application, and five had lung congestion, inflammation, or hemorrhage. Marginal increases were found in the incidence of lymphomas or leukemias (combined) as well as in the incidence of alveolar/bronchiolar adenomas or carcinomas (combined) in low dose male mice. Since there was no dose-related trend for these tumor incidences and because the increases were observed in only one sex, the increases were not considered to be related to the dermal application of 2-chloroethanol. 2-Chloroethanol was mutagenic in Salmonella typhimurium strains TA100 and TA1535 (but not TA1537 or TA98) in either the presence or the absence of Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver S9. 2-Chloroethanol did not induce sex-linked recessive lethal mutations in Drosophila melanogaster. An audit of the experimental data was conducted for these 2-year studies. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year dermal studies, there was no evidence of carcinogenicity of 2-chloroethanol for male and female F344/N rats given 50 or 100 mg/kg per day or for male and female Swiss CD-1 mice given 7.5 or 15 mg per animal per day. Synonyms: ethylene chlorohydrin; chloroethanol; glycol chlorohydrin; b-chloroethanol
PubMed: 12748704
DOI: No ID Found -
British Journal of Industrial Medicine Aug 1993Men assigned to the chlorohydrin unit of Union Carbide's South Charleston plant in the Kanawha Valley of West Virginia were followed up for mortality from 1940 to the...
Men assigned to the chlorohydrin unit of Union Carbide's South Charleston plant in the Kanawha Valley of West Virginia were followed up for mortality from 1940 to the end of 1988. This 10 year update was conducted to verify previous findings of excesses of cancer among the 278 men assigned to the chlorohydrin unit, which primarily produced ethylene chlorohydrin from 1925 to 1957. This process produced ethylene dichloride and bischloroethyl ether as byproducts. Mean duration of assignment was 5.9 years and mean duration of follow up was 36.5 years. Standardised mortality ratios (SMRs) were calculated based on comparisons with the United States white male population. Duration-response trends were assessed by internal comparisons with two different groups of unexposed chemical workers in the Kanawha Valley. The evidence that the earlier finding of an excess of pancreatic cancer was work related is strengthened by the occurrence of two additional cases (0.9 expected). The SMR for pancreatic cancer was 492 (95% CI 158-1140), based on eight observed v 1.6 expected deaths. There were no additional deaths due to leukaemia, but the three to four-fold excess risk for lymphopoietic cancers persisted due to new cases of non-Hodgkin's lymphoma and a death from multiple myeloma. The SMR for lymphatic and haematopoietic cancers was 294 (eight observed v 2.7 expected; 95% CI 127-580). Pronounced increases in risk were seen for total cancer, pancreatic cancer, all lymphatic and haematopoietic cancers, and leukaemia with increasing durations of assignment to the chlorohydrin unit. Most of the cases were first assigned to the unit in the 1930s when chemical manufacturing was in its infancy and exposures were less controlled. These data are insufficient to identify conclusively the causative agent or agents. The weight of evidence, however, based on probable exposure, known toxicity of the chemicals, and animal responses suggest that high exposures to ethylene dichloride, perhaps in combination with other chlorinated hydrocarbons, is the most likely explanation.
Topics: Adolescent; Adult; Aged; Chemical Industry; Chlorohydrins; Hematopoietic System; Humans; Leukemia; Lymphatic Diseases; Male; Middle Aged; Neoplasms; Occupational Diseases; Occupational Exposure; Pancreatic Neoplasms; Risk Factors; Time Factors; West Virginia
PubMed: 8398857
DOI: 10.1136/oem.50.8.710 -
Scientific Reports Jan 2019Because of its association with severe gastric pathologies, including gastric cancer, Helicobacter pylori has been subject of research for more than 30 years. Its...
Because of its association with severe gastric pathologies, including gastric cancer, Helicobacter pylori has been subject of research for more than 30 years. Its capacity to adapt and survive in the human stomach can be attributed to its genetic flexibility. Its natural competence and its capacity to turn genes on and off allows H. pylori to adapt rapidly to the changing conditions of its host. Because of its genetic variability, it is difficult to establish the uniqueness of each strain obtained from a human host. The methods considered to-date to deliver the best result for differentiation of strains are Rapid Amplification of Polymorphic DNA (RAPD), Multilocus Sequence Typing (MLST) and Whole Genome Sequencing (WGS) analysis. While RAPD analysis is cost-effective, it requires a stable genome for its reliability. MLST and WGS are optimal for strain identification, however, they require analysis of data at the bioinformatics level. Using the StainFree method, which modifies tryptophan residues on proteins using 2, 2, 2, - trichloroethanol (TCE), we observed a strain specific pattern of tryptophan in 1D acrylamide gels. In order to establish the effectiveness of tryptophan fingerprinting for strain identification, we compared the graphic analysis of tryptophan-labelled bands in the gel images with MLST results. Based on this, we find that tryptophan banding patterns can be used as an alternative method for the differentiation of H. pylori strains. Furthermore, investigating the origin for these differences, we found that H. pylori strains alters the number and/or position of tryptophan present in several proteins at the genetic code level, with most exchanges taking place in membrane- and cation-binding proteins, which could be part of a novel response of H. pylori to host adaptation.
Topics: DNA, Bacterial; Ethylene Chlorohydrin; Genome, Bacterial; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Multilocus Sequence Typing; Random Amplified Polymorphic DNA Technique; Reproducibility of Results; Sequence Analysis, DNA; Stomach Neoplasms; Tryptophan
PubMed: 30696868
DOI: 10.1038/s41598-018-37263-6 -
Archives of Disease in Childhood Mar 1975
Topics: Administration, Oral; Animals; Chlorohydrins; Ethanol; Ethylene Chlorohydrin; Humans; Rats
PubMed: 1147663
DOI: 10.1136/adc.50.3.250